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  • CLASSES

    Incretin mimetics Antidiabetics
    Other Antiobesity Products

    BOXED WARNING

    Medullary thyroid carcinoma (MTC), multiple endocrine neoplasia syndrome type 2 (MEN 2), thyroid cancer, thyroid C-cell tumors

    Liraglutide is contraindicated in patients with a personal or family history of certain types of thyroid cancer, specifically medullary thyroid carcinoma (MTC), or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Liraglutide has been shown to cause dose-dependent and treatment duration-dependent malignant thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. A statistically significant increase in cancer was observed in rats receiving liraglutide at 8-times clinical exposure compared to controls. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Cases of MTC in patients treated with liraglutide for diabetes have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. In clinical trials, there were 7 reported cases of papillary thyroid carcinoma in patients treated with liraglutide and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1,000 patient-years). Most of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and were diagnosed after thyroidectomy, which was prompted by finding on protocol-specified screening with serum calcitonin or thyroid ultrasound. Patients should be counseled on the potential risk and symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness). Although routine monitoring of serum calcitonin is of uncertain value in patients treated with liraglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

    DEA CLASS

    Rx

    DESCRIPTION

    Subcutaneous incretin mimetic (GLP-1 receptor agonist)
    Victoza is used to improve glycemic control in adults with type 2 diabetes mellitus (DM)and to reduce the risk of cardiovascular events (e.g., non-fatal myocardial infarction or non-fatal stroke), including reduction of cardiovascular mortality, if these patients also have cardiovascular disease
    Separate product (Saxenda) used for obesity as an adjunct to a reduced-calorie diet and increased physical activity in adults

    COMMON BRAND NAMES

    Saxenda, Victoza

    HOW SUPPLIED

    Saxenda/Victoza Subcutaneous Inj Sol: 1mL, 6mg

    DOSAGE & INDICATIONS

    For the treatment of type 2 diabetes mellitus and to reduce the risk of cardiovascular events (e.g., non-fatal myocardial infarction or non-fatal stroke), including reduction of cardiovascular mortality, in type 2 DM patients who also have established cardiovascular disease.
    Subcutaneous dosage (Victoza)
    Adults

    Initially, 0.6 mg subcutaneously once daily for 1 week. The 0.6 mg dose is a starting dose intended to reduce gastrointestinal (GI) symptoms during initial titration and is not effective for glycemic control. After 1 week, increase the dose to 1.2 mg subcutaneously once daily. If acceptable glycemic control not achieved, the dose can be increased to 1.8 mg subcutaneously once daily. If a dose is missed, resume the once daily regimen as prescribed with the next scheduled dose. If more than 3 days have elapsed since the last dose, reinitiate at 0.6 mg in order to alleviate any GI symptoms associated with re-initiation of treatment. The dose should then be re-titrated appropriately. The concurrent use of liraglutide and prandial insulin has not been studied. When liraglutide is added to insulin detemir, a reduction in the dose of insulin detemir may be needed to reduce the risk of hypoglycemia. The manufacturer of insulin detemir recommends initiating therapy with insulin detemir at 10 units subcutaneously once daily when combining with a GLP-1 receptor agonist. When initiating liraglutide, consider reducing the dose of concomitantly administered insulin secretagogues (e.g., sulfonylureas) to reduce the risk of hypoglycemia. In addition to improving glycemic control, a long-term, multicenter, randomized, double-blind, placebo-controlled clinical trial (LEADER) of 9,340 patients with inadequately controlled type 2 DM and established, stable, atherosclerotic cardiovascular disease reported that the risk of major adverse CV events (MACE: cardiovascular death, first occurrence of non-fatal myocardial infarction, or non-fatal stroke) was significantly reduced in the liraglutide group (13 %) compared to the placebo group (14.9%) (HR 0.87; 95% CI 0.78 to 0.97; p less than 0.001 for noninferiority; p = 0.01 for superiority).

    For the treatment of obesity as an adjunct to a reduced-calorie diet and increased physical activity.
    Subcutaneous dosage (Saxenda)
    Adults

    0.6 mg subcutaneously once daily for 1 week to reduce gastrointestinal (GI) symptoms associated with initial therapy. Increase the daily dose by 0.6 mg at weekly intervals until the target dose of 3 mg subcutaneously once daily is attained. If patients do not tolerate a dose increase, consider delaying dose escalation for 1 additional week. Discontinue liraglutide if patients cannot tolerate the 3 mg dose as efficacy has not been established at lower doses. If a dose is missed, resume the once daily regimen as prescribed with the next scheduled dose. If more than 3 days have elapsed since the last dose, reinitiate at the 0.6 mg dose and re-titrate appropriately. Liraglutide is indicated for patients with an initial body mass index (BMI) of 30 kg/m2 or more or in those with a BMI of 27 kg/m2 or more in the presence of at least 1 weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes). The BMI calculation = weight in kilograms divided by height in meters squared.

    Children† and Adolescents† 12 to 17 years

    Further study is needed to establish safety and efficacy. Preliminary studies suggest that a dosing regimen similar to that for obese adults may be appropriate for adolescent obese patients. In a small trial, pediatric patients (n = 21, age 12 to 17 years) at Tanner stage 2 to 5, with obesity [as defined by a body mass index (BMI) corresponding to both a BMI 95th percentile or more for age and sex and to a BMI of 30 kg/m2 for adults; additionally, BMI was 45 kg/m2 or less] were randomized (2:1) to receive 5 weeks of treatment with liraglutide (n = 14) or placebo (n = 7). Liraglutide was initiated at 0.6 mg subcutaneously once daily for 1 week to reduce gastrointestinal (GI) symptoms associated with initial therapy. The daily dose was increased by 0.6 mg at weekly intervals until the target dose of 3 mg subcutaneously once daily was attained. This was an exploratory study; gastrointestinal adverse effects were reported, and some hypoglycemia. Favorable effects of liraglutide in exploratory pharmacodynamic endpoints such as BMI, body weight, fasting glucose, A1C, were observed; none was statistically significant, but this was reflective of the short duration of treatment and the small number of participants.

    MAXIMUM DOSAGE

    Adults

    1.8 mg/day SC for the treatment of type 2 diabetes mellitus; 3 mg/day SC for the treatment of obesity.

    Geriatric

    1.8 mg/day SC for the treatment of type 2 diabetes mellitus; 3 mg/day SC for the treatment of obesity.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is required.  

    Renal Impairment

    No dosage adjustment is required.

    ADMINISTRATION

    Injectable Administration

    Administer by subcutaneous injection only. Do not administer by intravenous or intramuscular injection.
    Visually inspect for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use injections which are unusually viscous, cloudy, discolored, or if particles are present.
    Do NOT mix liraglutide with insulin. When using liraglutide (Victoza) concomitantly with insulin, administer as separate injections. The two injections may be injected in the same body region, but the injections should not be adjacent to each other.
    Liraglutide (Saxenda) for the treatment of obesity is not recommended in combination with insulin.
    Diabetic medication or other medication pens should never be shared among patients. Even if the disposable needle is changed, sharing may result in transmission of hepatitis viruses, HIV, or other blood-borne pathogens. Do not share pens among multiple patients in an inpatient setting; use multidose vials, if available, or reserve the use of any pen to 1 patient only.

    Subcutaneous Administration

    Administer once daily at any time of day, independently of meals.
    Liraglutide is available as a pre-filled pen.
    Pen needles are not included and must be purchased separately.
    Liraglutide pen should be used with Novo Nordisk disposable needles.
    The liraglutide pen must be primed prior to the first use. See the pen user manual for directions.
    Inject subcutaneously into the thigh, abdomen, or upper arm.
    Double-check dosage prior to administration.
    Press down on the center of the dose button to inject until 0 mg lines up with the pointer. Inject over 6 seconds to ensure the full dose is injected. Keep thumb on the injection button until the needle is removed from the skin.
    Rotate administration sites with each injection to prevent lipodystrophy.
    For patients who are to self administering liraglutide, adequate oral as well as written instructions on the use of the injector pen should be supplied before they self-administer a dose.
    Do not store the pen with the needle on; this will reduce the potential for contamination, infection, and leakage while also ensuring dosing accuracy.

    STORAGE

    Saxenda:
    - After initial use, may be stored for 30 days at controlled room temperature (59 to 86 degrees F) or in refrigerator (36 to 46 degrees F)
    - Avoid direct heat and sunlight
    - Avoid excessive heat (above 104 degrees F)
    - Discard 30 days after first use
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Do not use if product has been frozen
    - Refrigerate (between 36 and 46 degrees F)
    Victoza:
    - After initial use, may be stored for 30 days at controlled room temperature (59 to 86 degrees F) or in refrigerator (36 to 46 degrees F)
    - Avoid direct heat and sunlight
    - Avoid excessive heat (above 104 degrees F)
    - Discard 30 days after first use
    - Discard if product has been frozen
    - Do not freeze
    - Store unopened containers in refrigerator (36 to 46 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with liraglutide or any other antidiabetic drug.

    Angioedema, risk of serious hypersensitivity reactions or anaphylaxis

    Liraglutide is contraindicated in patients with a history of a serious hypersensitivity reaction to liraglutide. There is a risk of serious hypersensitivity reactions or anaphylaxis with liraglutide use. Serious hypersensitivity reactions have been reported during postmarketing use with liraglutide, such as anaphylaxis or angioedema. Use caution in patients with a history of angioedema to other GLP-1 receptor agonists because it is unknown whether such patients will be predisposed to angioedema with liraglutide. If a serious hypersensitivity reaction is suspected, discontinue liraglutide and consider other potential causes for the event, then initiate alternative therapy.

    Medullary thyroid carcinoma (MTC), multiple endocrine neoplasia syndrome type 2 (MEN 2), thyroid cancer, thyroid C-cell tumors

    Liraglutide is contraindicated in patients with a personal or family history of certain types of thyroid cancer, specifically medullary thyroid carcinoma (MTC), or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Liraglutide has been shown to cause dose-dependent and treatment duration-dependent malignant thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. A statistically significant increase in cancer was observed in rats receiving liraglutide at 8-times clinical exposure compared to controls. It is unknown whether liraglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Cases of MTC in patients treated with liraglutide for diabetes have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans. In clinical trials, there were 7 reported cases of papillary thyroid carcinoma in patients treated with liraglutide and 1 case in a comparator-treated patient (1.5 vs. 0.5 cases per 1,000 patient-years). Most of these papillary thyroid carcinomas were less than 1 cm in greatest diameter and were diagnosed after thyroidectomy, which was prompted by finding on protocol-specified screening with serum calcitonin or thyroid ultrasound. Patients should be counseled on the potential risk and symptoms of thyroid tumors (e.g. a mass in the neck, dysphagia, dyspnea or persistent hoarseness). Although routine monitoring of serum calcitonin is of uncertain value in patients treated with liraglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

    Diabetic ketoacidosis, type 1 diabetes mellitus

    Liraglutide is not a substitute for insulin in patients who require insulin. Liraglutide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Liraglutide has not been evaluated for use in combination with prandial insulin.

    Burns, diarrhea, fever, infection, surgery, thyroid disease, trauma, vomiting

    Diabetic patients must follow a regular, prescribed diet and exercise schedule to avoid either hypo- or hyperglycemia. Fever, thyroid disease, infection, recent trauma or surgery, diarrhea secondary to malabsorption, vomiting, and certain medications can affect requirements of antidiabetic agents; dosage adjustments may be necessary. Diabetic patients should be given a 'sick-day' plan to take appropriate action with blood glucose monitoring and their antidiabetic therapy, including liraglutide, when acute illness is present. Temporary use of insulin in place of oral antidiabetic agents may be necessary during periods of physiologic stress (e.g., burns, systemic infection, trauma, surgery, or fever).

    Gastroparesis

    Liraglutide may slow gastric emptying. Liraglutide has not been studied in patients with gastroparesis, and should be used cautiously in this population. Its use is commonly associated with gastrointestinal adverse effects, including nausea, vomiting, and diarrhea.

    Hypoglycemia

    Hypoglycemia should be monitored for by the patient and clinician when liraglutide treatment is initiated and continued. In clinical trials, hypoglycemia was increased when liraglutide was used in combination with a sulfonylurea. Although specific dose recommendations are not available, the clinician should consider a dose reduction of the sulfonylurea when used in combination with liraglutide. In addition, when liraglutide is used in combination with insulin detemir, the dose of insulin should be evaluated; in patients at increased risk of hypoglycemia consider reducing the dose of insulin at initiation of liraglutide, followed by careful titration. Adequate blood glucose monitoring should be continued and followed. Patient and family education regarding hypoglycemia management is crucial; the patient and patient's family should be instructed on how to recognize and manage the symptoms of hypoglycemia. Early warning signs of hypoglycemia may be less obvious in patients with hypoglycemia unawareness which can be due to a long history of diabetes (where deficiencies in the release or response to counter regulatory hormones exist), with autonomic neuropathy, intensified diabetes control, or taking beta-blockers, guanethidine, or reserpine. Patients should be aware of the need to have a readily available source of glucose (dextrose, d-glucose) or other carbohydrate to treat hypoglycemic episodes. In severe hypoglycemia, intravenous dextrose or glucagon injections may be needed. Because hypoglycemic events may be difficult to recognize in some elderly patients, antidiabetic agent regimens should be carefully managed to obviate an increased risk of severe hypoglycemia. Severe or frequent hypoglycemia in a patient is an indication for the modification of treatment regimens, including setting higher glycemic goals.

    Renal impairment

    Use caution when initiating or increasing doses of liraglutide in patients with renal impairment. There is limited information available on the use of liraglutide in patients with renal impairment. Although liraglutide has not been found to be directly nephrotoxic in animal studies or clinical trials, there have been post-marketing reports of acute renal failure and worsening of chronic renal failure, which sometimes has required hemodialysis in patients treated with liraglutide; in many of these cases, altered renal function has been reversed with supportive treatment and discontinuation of potentially causative agents, including liraglutide. In addition, the pharmacokinetics of a single dose of liraglutide were evaluated in patients with varying degrees of renal impairment. Compared to healthy subjects, the AUC in patients with varying degrees of renal impairment was lower.

    Alcoholism, cholelithiasis, gallbladder disease, pancreatitis

    Use liraglutide with caution in patients with risk factors for pancreatitis. Liraglutide has been studied in a limited number of patients with a history of pancreatitis; it is unknown if these patients are at increased risk for the development of pancreatitis while using liraglutide. There have been reports of acute and chronic pancreatitis in patients taking liraglutide during premarketing clinical trials. In some of these patients other risk factors for pancreatitis were present, such as gallstones (cholelithiasis) or alcoholism. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has also been reported postmarketing in patients treated with liraglutide. Liraglutide has been studied in a limited number of patients with a history of pancreatitis; it is unknown if these patients are at increased risk for the development of pancreatitis while using liraglutide. The FDA and EMA have evaluated unpublished findings that suggested an increased risk of pancreatitis and pre-cancerous cellular changes called pancreatic duct metaplasia in patients treated with incretin mimetics. These findings were based on examination of a small number of pancreatic tissue specimens taken from patients after they died from unspecified causes. The FDA and the EMA have stated that after review, the current data do not support an increased risk of pancreatitis and pancreatic cancer in patients receiving incretin mimetics. The agencies have not reached any new conclusions about safety risks of the incretin mimetics, although they have expressed that the totality of the data that have been reviewed provides reassurance. Recommendations will be communicated once the review is complete; continue to consider precautions related to pancreatic risk until more data are available. After initiation and dose increases, patients should be observed carefully for signs and symptoms of pancreatitis (including persistent severe abdominal pain, sometimes radiating to the back and which may or may not be accompanied by vomiting). If pancreatitis is suspected, discontinue liraglutide; if pancreatitis is confirmed do not resume liraglutide. Also use liraglutide with caution in patients with gallbladder disease. In the LEADER trial, 3.1% of liraglutide-treated patients versus 1.9% of placebo-treated patients reported an acute gallbladder disease events, such as cholelithiasis or cholecystitis. The majority of events required hospitalization or cholecystectomy. In patients for whom cholelithiasis is suspected, also consider evaluation for an acute gallbladder disease event and perform gallbladder studies and appropriate clinical follow-up.

    Hepatic disease

    There is limited information available on the use of liraglutide in patients with hepatic disease. The pharmacokinetics of a single dose of liraglutide were evaluated in patients with varying degrees of hepatic disease. Compared to healthy subjects, the AUC in patients with hepatic impairment was lower (see Pharmacokinetics). Liraglutide should be used with caution in patients with hepatic disease.

    Pregnancy

    Liraglutide (Saxenda) for the treatment of obesity is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm due to the potential hazard of maternal weight loss to the fetus. There are no adequate data or clinical studies of liraglutide (Victoza) use for the treatment of type 2 diabetes mellitus in pregnant women; use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the toxicities found in animal studies, it may be prudent to avoid liraglutide until data in human pregnancy are available. Rat studies have noted abnormalities and variations in the kidneys, and irregular skeletal ossification effects when liraglutide was given at or above 0.8 times the human systemic exposures, based on the maximum recommended human dose (MRHD) of 1.8 mg/day (determined from AUC). Reduced growth and increased total major abnormalities occurred in rabbits at systemic exposures below human exposure at the MRHD (determined from AUC). The American College of Obstetrician and Gynecologists recommends insulin as the therapy of choice to maintain blood glucose as close to normal as possible during pregnancy in patients with type 1 or 2 diabetes mellitus, and, if diet therapy alone is not successful, for those patients with gestational diabetes.

    Breast-feeding

    In lactating rats, liraglutide was excreted unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. Liraglutide excretion into human milk is unknown. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for liraglutide in animal studies, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. If liraglutide is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected. Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies. The American Academy of Pediatrics (AAP) regards tolbutamide as usually compatible with breast-feeding. Although other sulfonylureas have not been evaluated by the AAP, glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide. If any oral hypoglycemics are used during breast feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.

    Children, infants

    The safety and efficacy of liraglutide have not been established in adolescents, children, or infants.

    Depression, suicidal ideation

    When liraglutide is used for weight management, administer with caution in patients with depression and avoid use in patients with a history of suicide attempts or active suicidal ideation. Monitor patients receiving liraglutide for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue liraglutide in patients who develop suicidal thoughts or behaviors. In clinical trials of liraglutide (Saxenda) for the treatment of obesity, 0.3% of patients receiving liraglutide reported suicidal ideation compared to 0.1% of the patients receiving placebo; one of these liraglutide-treated patients attempted suicide.

    Geriatric

    Liraglutide has been studied in patients 65 years of age or older during clinical trials; safety and efficacy were not different in geriatric patients versus younger adult patients. In general, however, elderly patients are especially at risk for hypoglycemic episodes. The specific reasons identified include intensive insulin therapy, decreased renal function, severe liver disease, alcohol ingestion, defective counter regulatory hormone release, missing meals/fasting, and gastroparesis. Because hypoglycemic events may be difficult to recognize in some elderly patients, antidiabetic agent regimens should be carefully managed to obviate an increased risk of severe hypoglycemia. Severe or frequent hypoglycemia is an indication for the modification of treatment regimens, including setting higher glycemic goals. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, the use of antidiabetic medications should include monitoring (e.g., periodic blood glucose) for effectiveness based on desired goals for that individual and to identify complications of treatment such as hypoglycemia or impaired renal function.

    ADVERSE REACTIONS

    Severe

    cholecystitis / Delayed / 0.2-3.1
    pancreatitis / Delayed / 0-0.3
    AV block / Early / 0.3-0.3
    suicidal ideation / Delayed / 0.3-0.3
    angioedema / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    palpitations / Early / 0-34.0
    hypoglycemia / Early / 1.6-23.0
    constipation / Delayed / 9.9-19.4
    antibody formation / Delayed / 8.6-8.6
    cholelithiasis / Delayed / 0.3-3.1
    hypertension / Early / 3.0-3.0
    erythema / Early / 0-2.0
    hypotension / Rapid / 1.1-1.1
    orthostatic hypotension / Delayed / 1.1-1.1
    sinus tachycardia / Rapid / 0.6-0.6
    bundle-branch block / Early / 0.3-0.3
    elevated hepatic enzymes / Delayed / 0.2-0.2
    secondary malignancy / Delayed / 0.2-0.2
    hyperamylasemia / Delayed / 0.1-0.1
    gastritis / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    edema / Delayed / Incidence not known

    Mild

    nausea / Early / 23.9-39.0
    diarrhea / Early / 9.3-17.1
    vomiting / Early / 8.7-15.7
    injection site reaction / Rapid / 2.0-13.9
    anorexia / Delayed / 10.0-10.0
    dyspepsia / Early / 9.6-9.6
    headache / Early / 9.1-9.1
    fatigue / Early / 7.5-7.5
    influenza / Delayed / 7.4-7.4
    infection / Delayed / 4.3-6.0
    dizziness / Early / 5.8-5.8
    sinusitis / Delayed / 5.6-5.6
    abdominal pain / Early / 5.4-5.4
    back pain / Delayed / 5.0-5.0
    gastroesophageal reflux / Delayed / 4.7-4.7
    eructation / Early / 4.5-4.5
    flatulence / Early / 4.0-4.0
    insomnia / Early / 2.4-2.4
    xerostomia / Early / 2.3-2.3
    asthenia / Delayed / 2.1-2.1
    anxiety / Delayed / 2.0-2.0
    dysgeusia / Early / Incidence not known
    rash (unspecified) / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    malaise / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration. (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Butalbital: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Butalbital; Caffeine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Caffeine; Dihydrocodeine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration. (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration. (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Codeine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dextromethorphan: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Diphenhydramine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Guaifenesin; Phenylephrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Hydrocodone: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Oxycodone: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Pentazocine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Propoxyphene: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Pseudoephedrine: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetaminophen; Tramadol: (Minor) Liraglutide did not change the AUC of acetaminophen following a single dose of acetaminophen 1000 mg, administered 8 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of acetaminophen was decreased by 31% and the median Tmax of acetaminophen was delayed up to 15 minutes. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If acetaminophen and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered acetaminophen effect.
    Acetazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Aliskiren; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Amlodipine; Atorvastatin: (Minor) Liraglutide did not change the AUC of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of atorvastatin was decreased by 38% and the median Tmax of atorvastatin was delayed from 1 hour to 3 hours. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If atorvastatin and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered atorvastatin effect.
    Amlodipine; Benazepril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Amlodipine; Olmesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Amlodipine; Telmisartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Amlodipine; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Amprenavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Androgens: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Angiotensin II receptor antagonists: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Angiotensin-converting enzyme inhibitors: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Aspirin, ASA: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Carisoprodol: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Dipyridamole: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Omeprazole: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Oxycodone: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Aspirin, ASA; Pravastatin: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Atazanavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Atazanavir; Cobicistat: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Atorvastatin: (Minor) Liraglutide did not change the AUC of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of atorvastatin was decreased by 38% and the median Tmax of atorvastatin was delayed from 1 hour to 3 hours. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If atorvastatin and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered atorvastatin effect.
    Atorvastatin; Ezetimibe: (Minor) Liraglutide did not change the AUC of atorvastatin following a single dose of atorvastatin 40 mg, administered 5 hours after a dose of liraglutide 1.8 mg at steady state; however, the Cmax of atorvastatin was decreased by 38% and the median Tmax of atorvastatin was delayed from 1 hour to 3 hours. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If atorvastatin and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered atorvastatin effect.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    atypical antipsychotic: (Moderate) Patients taking incretin mimetics should be closely monitored for worsening glycemic control when an atypical antipsychotic is instituted. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. Changes in lipid profiles and weight may also aggravate diabetes or associated conditions or complications. Temporal associations of atypical antipsychotic therapy with the aggravation or new onset of diabetes mellitus have been reported.
    Azelaic Acid; Copper; Folic Acid; Nicotinamide; Pyridoxine; Zinc: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
    Azilsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Azilsartan; Chlorthalidone: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Baclofen: (Minor) Because baclofen can increase blood glucose, doses of antidiabetic agents may need adjustment in patients receiving these drugs concomitantly.
    Benazepril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Beta-blockers: (Moderate) Beta-adrenergic blockade may prevent the appearance of certain premonitory signs and symptoms (pulse rate and pressure changes) of acute hypoglycemia. Other manifestations such as dizziness and sweating may not be significantly affected. Beta-blockers exert complex actions on the body's ability to regulate blood glucose. Some beta-blockers, particularly non-selective beta-blockers such as propranolol, have been associated with potentiation of insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Selective beta-blockers, such as atenolol or metoprololl, do not appear to potentiate insulin-induced hypoglycemia. Hypoglycemia has been reported in patients taking non-selective beta-blockers during fasting for preparation for surgery, after prolonged physical exertion and in patients with renal insufficiency. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes. Furthermore, their use should not be avoided in patients with compelling indications for beta-blocker therapy (i.e., post-MI, heart failure, etc.) when no other contraindications are present. Decreased mortality has been shown in the post-MI and heart failure populations when beta-blockers are used, especially in patients with coexisting diabetes mellitus.
    Bexarotene: (Moderate) Bexarotene may enhance the hypoglycemic action of exenatide. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving bexarotene in combination with exenatide.
    Bismuth Subsalicylate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Bortezomib: (Minor) During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients on antidiabetic agents receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medications.
    Candesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Captopril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Carbonic anhydrase inhibitors: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Chloroquine: (Major) Careful monitoring of blood glucose is recommended when chloroquine and antidiabetic agents, including the incretin mimetics, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with chloroquine and an antidiabetic agent.
    Chlorpromazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Chlorthalidone; Clonidine: (Moderate) Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents and may mask the signs and symptoms of hypoglycemia. While clonidine has not been shown to significantly impair glucose tolerance in most human studies, patients receiving this combination should be monitored for changes in glycemic control.
    Choline Salicylate; Magnesium Salicylate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Chromium: (Moderate) Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended.
    Ciprofloxacin: (Moderate) Careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, including the incretin mimetics, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent.
    Clonidine: (Moderate) Clonidine may potentiate or weaken the hypoglycemic effects of antidiabetic agents and may mask the signs and symptoms of hypoglycemia. While clonidine has not been shown to significantly impair glucose tolerance in most human studies, patients receiving this combination should be monitored for changes in glycemic control.
    Codeine; Phenylephrine; Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Codeine; Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Conjugated Estrogens; Medroxyprogesterone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Corticosteroids: (Moderate) When corticosteroids are administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Endogenous counter-regulatory hormones such as glucocorticoids are released in response to hypoglycemia and cause blood glucose concentrations to rise. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when corticosteroids are instituted.
    Cyclosporine: (Moderate) Cyclosporine has been reported to cause hyperglycemia. It may have direct beta-cell toxicity; the effects may be dose-related. Patients should be monitored for worsening of glycemic control if therapy with cyclosporine is initiated in patients receiving antidiabetic agents, including incretin mimetics.
    Danazol: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Darunavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Darunavir; Cobicistat: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Desiccated Thyroid: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Dextromethorphan; Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Diazoxide: (Minor) Diazoxide increases blood glucose by inhibiting insulin release from the pancreas and/or by stimulating the release of catecholamines, which in turn stimulate glycogenolysis. The dosage of the incretin mimetic may need to be adjusted when diazoxide is added to the regimen. Carefully monitor blood glucose concentrations when diazoxide is combined with an incretin mimetic.
    Dienogest; Estradiol valerate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Digoxin: (Minor) A single dose of digoxin 1 mg administered 7 hours after a dose of liraglutide 1.8 mg at steady state resulted in a reduction of the digoxin AUC by 16% and Cmax by 31%. The median Tmax for digoxin was delayed from 1 hour to 1.5 hours. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If digoxin and liraglutide are co-prescribed, it may be prudent to initially monitor the patient for altered digoxin effect.
    Disopyramide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
    Drospirenone; Estradiol: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Drospirenone; Ethinyl Estradiol: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Enalapril, Enalaprilat: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Enalapril; Felodipine: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Eprosartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Esterified Estrogens; Methyltestosterone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Estradiol Cypionate; Medroxyprogesterone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Estradiol; Levonorgestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Estradiol; Norethindrone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Estradiol; Norgestimate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Estrogens: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as combined hormonal oral contraceptives (OCs). Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, estrogens can impair glucose tolerance. Changes in glucose tolerance occur more commonly in patients receiving greater than 50 mcg of ethinyl estradiol or equivalent estrogen per day. However, any patient with diabetes may need to monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethanol: (Moderate) Alcohol (ethanol) may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy. Alcohol ingestion can decrease endogenous glucose production potentiating the risk of hypoglycemia. Alternatively, alcohol can worsen glycemic control as it provides a source of additional calories. Blood glucose concentrations should be closely monitored. Patients should be encouraged to limit or moderate their intake of alcoholic beverages. Because of its effects on endogenous glucose production, patients should be encouraged to avoid alcohol ingestion during the fasting state. Many non-prescription drug products may be formulated with ethanol; have patients scrutinize product labels prior to consumption.
    Ethinyl Estradiol; Desogestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Etonogestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Levonorgestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norethindrone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norgestimate: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethinyl Estradiol; Norgestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Ethotoin: (Minor) The hydantoin anticonvulsants ethotoin, fosphenytoin and phenytoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued.
    Etonogestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Fibric acid derivatives: (Moderate) Fibric acid derivatives may enhance the hypoglycemic effects of incretin mimetics through increased insulin sensitivity and decreased glucagon secretion. Patients receiving this combination should be monitored for changes in glycemic control.
    Fluoxetine: (Moderate) Fluoxetine may enhance the hypoglycemic effects of incretin mimetics. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents.
    Fluoxetine; Olanzapine: (Moderate) Fluoxetine may enhance the hypoglycemic effects of incretin mimetics. Serum glucose should be monitored closely when fluoxetine is added to any regimen containing antidiabetic agents.
    Fluoxymesterone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Fluphenazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Fosamprenavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Fosinopril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Fosphenytoin: (Minor) The hydantoin anticonvulsants ethotoin, fosphenytoin and phenytoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued.
    Garlic, Allium sativum: (Moderate) Limited animal data suggest that selected constituents in Garlic might have some antidiabetic activity, resulting in increased serum insulin concentrations and increased glycogen storage in the liver. Patients with diabetes frequently purchase alternative remedies that have been purported to improve glycemic control, but there is no scientific or controlled evidence in humans of this action. Limited clinical evidence suggests that garlic does not affect blood glucose in those without diabetes. Until more data are available, individuals receiving antidiabetic agents should use caution in consuming dietary supplements containing garlic, and follow their normally recommended strategies for blood glucose monitoring.
    Gemifloxacin: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones, such as gemifloxacin, and an antidiabetic agent, including incretin mimetics. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, are coadministered.
    Glucagon: (Minor) Endogenous counter-regulatory hormones such as glucagon are released in response to hypoglycemia. When released, blood glucose concentrations rise. When glucagon is administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of incretin mimetics. Clinically, glucagon is often used to increase blood glucose concentrations in patients with severe hypoglycemia.
    Green Tea: (Moderate) Green tea catechins have been shown to decrease serum glucose concentrations in vitro. Patients with diabetes mellitus taking incretin mimetics should be monitored closely for hypoglycemia if consuming green tea.
    Griseofulvin: (Minor) During coadministration with liraglutide, the Cmax of griseofulvin increased by 37% while the median Tmax and AUC remained unchanged. The mechanism of the interaction is not known, nor is the clinical significance of this potential interaction. If co-prescribed, it may be prudent to initially monitor for altered griseofulvin effect.
    Guarana: (Major) Caffeine, an active constituent of guarana, is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. Use of guarana should be avoided with amphetamine, dextroamphetamine, methylphenidate, modafinil, pemoline, pseudoephedrine, beta-agonists or other sympathomimetics. When combined with any of these medications, nervousness, irritability, insomnia, and/or cardiac arrhythmias may result.
    Hydantoins: (Minor) The hydantoin anticonvulsants ethotoin, fosphenytoin and phenytoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Hydrochlorothiazide, HCTZ; Triamterene: (Minor) Triamterene can decrease the hypoglycemic effects of antidiabetic agents, such as incretin mimetics, by producing an increase in blood glucose levels. Patients on antidiabetics should be monitored for changes in blood glucose control if triamterene is added or deleted. Dosage adjustments may be necessary.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Hydroxychloroquine: (Major) Careful monitoring of blood glucose is recommended when hydroxychloroquine and antidiabetic agents, including the incretin mimetics, are coadministered. A decreased dose of the antidiabetic agent may be necessary as severe hypoglycemia has been reported in patients treated concomitantly with hydroxychloroquine and an antidiabetic agent.
    Hydroxyprogesterone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Indapamide: (Moderate) A potential pharmacodynamic interaction exists between indapamide and antidiabetic agents, like incretin mimetics. Indapamide can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia.
    Indinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Insulin Aspart: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin aspart because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Degludec: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin degludec because of the risk of hypoglycemia. When liraglutide is used with insulin for the treatment of diabetes, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Degludec; Liraglutide: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin degludec because of the risk of hypoglycemia. When liraglutide is used with insulin for the treatment of diabetes, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Detemir: (Major) Liraglutide used for weight loss should not be given concomitantly with insulin detemir because of the risk of hypoglycemia. When liraglutide is added to insulin detemir for the treatment of diabetes, a reduction in the dose of insulin detemir may be needed to reduce the risk of hypoglycemia. The manufacturer of insulin detemir recommends initiating therapy with insulin detemir at 10 Units subcutaneously once daily when combining with a GLP-1 receptor agonist, such as liraglutide. Blood glucose concentrations should be closely monitored.
    Insulin Glargine: (Moderate) Liraglutid used for weight loss should not be given concomitantly with insulin glargine because of the risk of hypoglycemia. When liraglutide is used with insulin glargine for the treatment of diabetes, consider lowering the dose of the insulin glargine to reduce the risk of hypoglycemia and increase the frequency of blood glucose monitoring.
    Insulin Glargine; Lixisenatide: (Moderate) Liraglutid used for weight loss should not be given concomitantly with insulin glargine because of the risk of hypoglycemia. When liraglutide is used with insulin glargine for the treatment of diabetes, consider lowering the dose of the insulin glargine to reduce the risk of hypoglycemia and increase the frequency of blood glucose monitoring.
    Insulin Glulisine: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin glulisine because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Lispro: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin lispro because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Lispro: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin lispro because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Lispro; Insulin Lispro Protamine: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin lispro because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin Regular: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin regular because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Insulin, Inhaled: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Irbesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Isocarboxazid: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Isoniazid, INH: (Minor) Although rare, isoniazid, INH may increase blood sugar. Antidiabetic agent requirements may be increased when patients are administered isoniazid, INH concomitantly. Patients should be closely monitored for changes in glycemic control if isoniazid therapy is initiated or discontinued.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Although rare, isoniazid, INH may increase blood sugar. Antidiabetic agent requirements may be increased when patients are administered isoniazid, INH concomitantly. Patients should be closely monitored for changes in glycemic control if isoniazid therapy is initiated or discontinued.
    Isoniazid, INH; Rifampin: (Minor) Although rare, isoniazid, INH may increase blood sugar. Antidiabetic agent requirements may be increased when patients are administered isoniazid, INH concomitantly. Patients should be closely monitored for changes in glycemic control if isoniazid therapy is initiated or discontinued.
    Lanreotide: (Moderate) Monitor blood glucose levels if administration of lanreotide is necessary with antidiabetic agents; adjust the dosage of the antidiabetic agent as clinically appropriate. Lanreotide inhibits the secretion of insulin and glucagon.
    Leuprolide; Norethindrone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Levocarnitine: (Moderate) Chromium dietary supplements may lower blood glucose. As part of the glucose tolerance factor molecule, chromium appears to facilitate the binding of insulin to insulin receptors in tissues and to aid in glucose metabolism. Because blood glucose may be lowered by the use of chromium, patients who are on antidiabetic agents may need dose adjustments. Close monitoring of blood glucose is recommended.
    Levofloxacin: (Moderate) Careful monitoring of blood glucose is recommended when levofloxacin and antidiabetic agents, including the incretin mimetics, are coadministered. Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent.
    Levonorgestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Levothyroxine: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Linezolid: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Liothyronine: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Liotrix: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Lisinopril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Lithium: (Moderate) Lithium may cause variable effects on glycemic control when used in patients receiving antidiabetic therapy iincluding incretin mimetics. Blood glucose concentrations should be closely monitored if lithium is taken by the patient. Dosage adjustments of insulin may be necessary.
    Lomefloxacin: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are co-administered.
    Loop diuretics: (Minor) Loop diuretics, such as bumetanide, furosemide, and torsemide, may cause hyperglycemia and glycosuria in patients with diabetes mellitus, probably due to diuretic-induced hypokalemia. Because of this, a potential pharmacodynamic interaction exists between these drugs and all antidiabetic agents, including incretin mimetics. This interference can lead to a loss of diabetic control, so diabetic patients should be monitored closely if these drugs are initiated.
    Lopinavir; Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Lorcaserin: (Moderate) In general, weight reduction may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with antidiabetic agents, such as insulin and/or insulin secretagogues (e.g., sulfonylureas). In clinical trials, lorcaserin use was associated with reports of hypoglycemia. Blood glucose monitoring is warranted in patients with type 2 diabetes prior to starting and during lorcaserin treatment. Dosage adjustments of anti-diabetic medications should be considered. If a patient develops hypoglycemia during treatment, adjust anti-diabetic drug regimen accordingly. Of note, lorcaserin has not been studied in combination with insulin.
    Losartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Lovastatin; Niacin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
    Magnesium Salicylate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Mecasermin rinfabate: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Although the rh-IGF-1/rh-IGFBP-3 complex has less propensity to rapidly lower blood glucose compared to unbound mecasermin, hypoglycemia is possible with either agent. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin (rh-IGF-1) has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms.
    Mecasermin, Recombinant, rh-IGF-1: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 and mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. Although the rh-IGF-1/rh-IGFBP-3 complex has less propensity to rapidly lower blood glucose compared to unbound mecasermin, hypoglycemia is possible with either agent. The amino acid sequence of mecasermin (rh-IGF-1) is approximately 50 percent homologous to insulin and cross binding with either receptor is possible. Treatment with mecasermin (rh-IGF-1) has been shown to improve insulin sensitivity and to improve glycemic control in patients with either Type 1 or Type 2 diabetes mellitus when used alone or in conjunction with insulins. Patients should be advised to eat within 20 minutes of mecasermin administration. Glucose monitoring is important when initializing or adjusting mecasermin therapies, when adjusting concomitant antidiabetic therapy, and in the event of hypoglycemic symptoms.
    Medroxyprogesterone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Megestrol: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Meperidine; Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Mesoridazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Mestranol; Norethindrone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Methazolamide: (Minor) Carbonic anhydrase inhibitors may alter blood sugar. Both hyperglycemia and hypoglycemia have been described in patients treated with acetazolamide. This should be taken into consideration in patients with impaired glucose tolerance or diabetes mellitus who are receiving antidiabetic agents. Monitor blood glucose and for changes in glycemic control and be alert for evidence of an interaction.
    Methyltestosterone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Metoclopramide: (Moderate) Metoclopramide can enhance gastric emptying in patients with diabetes. Typically, blood glucose could be affected, which, in turn, may affect the clinical response to antidiabetic agents. However, incretin mimetics have been shown to slow gastric emptying. The clinical effects of these competing mechanisms are not known. The dosing of antidiabetic agents may require adjustment in patients who receive metoclopramide. Blood glucose should be closely monitored and antidiabetic agents adjusted accordingly in this situation.
    Metyrapone: (Moderate) In patients taking insulin or other antidiabetic agents, the signs and symptoms of acute metyrapone toxicity (e.g., symptoms of acute adrenal insufficiency) may be aggravated or modified.
    Moexipril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Monoamine oxidase inhibitors: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Moxifloxacin: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones, such as moxifloxacin, and an antidiabetic agent, including incretin mimetics. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, are coadministered.
    Nandrolone Decanoate: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Nebivolol; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Nelfinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Niacin, Niacinamide: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
    Niacin; Simvastatin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. When used at daily doses of 750 to 2,000 mg, niacin significantly lowers LDL cholesterol and triglycerides while increasing HDL cholesterol. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients on antidiabetic therapy for blood glucose control if niacin (nicotinic acid) is added or deleted to the medication regimen and adjust dosages as clinically warranted
    Nicotine: (Minor) Monitor blood glucose concentrations for needed antidiabetic agent dosage adjustments in diabetic patients whenever a change in either nicotine intake or smoking status occurs. Nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. Tobacco smoking is known to aggravate insulin resistance. Cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose.
    Norethindrone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Norfloxacin: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones and an antidiabetic agent. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered.
    Norgestrel: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Octreotide: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Ofloxacin: (Moderate) Disturbances of blood glucose, including hyperglycemia and hypoglycemia, have been reported in patients treated concomitantly with quinolones, such as ofloxacin, and an antidiabetic agent, including incretin mimetics. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents, are coadministered.
    Olmesartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Orlistat: (Minor) Changes in dietary intake and weight loss induced by orlistat may improve metabolic control in diabetic patients. Lower blood glucose may necessitate a dosage reduction of antidiabetic agents, including exenatide.
    Oxandrolone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Oxymetholone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Pasireotide: (Major) Pasireotide may cause hyperglycemia. Closely monitor patients receiving antidiabetic therapy for changes in glycemic control; adjustments in the dosage of antidiabetic agents may be necessary during pasireotide receipt and after its discontinuation.
    Pegvisomant: (Moderate) Patients who have both acromegaly and diabetes mellitus and are being treated with oral antidiabetic agents may require dose reductions of these medications after the initiation of pegvisomant. Growth hormone decreases insulin sensitivity by opposing the effects of insulin on carbohydrate metabolism; therefore, pegvisomant, which antagonizes growth hormone, is expected to have the opposite effect. Although none of the acromegalic patients with diabetes mellitus who were treated with pegvisomant during the clinical studies developed clinically relevant hypoglycemia, such patients should monitor their blood glucose regularly, with doses of antidiabetic medications reduced as necessary.
    Pentamidine: (Moderate) Pentamidine can be harmful to pancreatic cells. This effect may lead to hypoglycemia acutely, followed by hyperglycemia with prolonged pentamidine therapy. Patients on antidiabetic agents should be monitored for the need for dosage adjustments during the use of pentamidine.
    Pentoxifylline: (Moderate) Pentoxiphylline has been used concurrently with antidiabetic agents without observed problems, but it may enhance the hypoglycemic action of antidiabetic agents. Patients should be monitored for changes in glycemic control while receiving pentoxifylline in combination with antidiabetic agents.
    Perindopril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Perindopril; Amlodipine: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Perphenazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Perphenazine; Amitriptyline: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Phenelzine: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Phenothiazines: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Phenylephrine; Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Phenytoin: (Minor) The hydantoin anticonvulsants ethotoin, fosphenytoin and phenytoin can decrease the hypoglycemic effects of incretin mimetics by producing an increase in blood glucose levels. Patients receiving incretin mimetics should be closely monitored for signs indicating loss of diabetic control when therapy with a hydantoin is instituted. Conversely, patients should be closely monitored for signs of hypoglycemia when therapy with a hydantoin is discontinued.
    Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Prochlorperazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Progesterone: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Progestins: (Moderate) Incretin mimetics slow gastric emptying and should be used with caution in patients receiving oral medications that require minimum threshold concentrations for efficacy, such as progestin-only oral contraceptives. Some incretin mimetics make specific recommendations to reduce the risk for interaction. Taking an oral contraceptive (OC) at least 1 hour before an incretin mimetic injection should reduce the risk of an effect on contraceptive or hormonal absorption. For Lixisenatide, the manufacturer recommends taking the OC 1 hour before injection or 11 hours after injection to reduce the effect on absorption. Additionally, progestins can impair glucose tolerance. Monitor blood glucose more carefully during initiation or discontinuation of hormone replacement or hormonal contraceptive treatment. Patients receiving incretin mimetics should be closely monitored for changes in glycemic control.
    Promethazine: (Minor) It is unclear if phenothiazines directly interact with antidiabetic agents, phenothiazines have been reported to increase blood glucose concentrations. Since promethazine is a phenothiazine antihistamine, it should be used cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Protease inhibitors: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Quinapril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Ramipril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Rasagiline: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor rasagiline, are added to any regimen containing antidiabetic agents.
    Regular Insulin: (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin regular because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Regular Insulin; Isophane Insulin (NPH): (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin isophane (NPH insulin) because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently. (Moderate) Liraglutide used for weight loss should not be given concomitantly with insulin regular because of the risk of hypoglycemia. Liraglutide for the treatment of diabetes has not been studied in combination with prandial insulin. When liraglutide is used with insulin, consider lowering the dose of the insulin to reduce the risk of hypoglycemia and monitor the blood glucose concentration more frequently.
    Reserpine: (Moderate) Reserpine may mask the signs and symptoms of hypoglycemia. Patients receiving reserpine concomitantly with antidiabetic agents, such as incretin mimetics, should be monitored for changes in glycemic control.
    Ritonavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Sacubitril; Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Salicylates: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Salsalate: (Moderate) Salicylates, by inhibiting prostaglandin E2 synthesis, can indirectly increase insulin secretion. Thus, salicylates can decrease blood glucose concentrations. In large doses, salicylates uncouple oxidative phosphorylation, deplete hepatic and muscle glycogen, and cause hyperglycemia and glycosuria. After acute overdose, aspirin can cause either hypo- or hyperglycemia. Large doses of aspirin should be used cautiously in patients receiving antidiabetic agents. Monitor blood glucose closely during coadministration.
    Saquinavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Selegiline: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Somatropin, rh-GH: (Minor) Endogenous counter-regulatory hormones such as growth hormone are released in response to hypoglycemia. When released, blood glucose concentrations rise. When somatropin, rh-GH, growth hormone is administered exogenously, increases in blood glucose concentrations would be expected thereby decreasing the hypoglycemic effect of antidiabetic agents. Patients receiving antidiabetic agents should be closely monitored for signs indicating loss of diabetic control when growth hormone is instituted.
    Sparfloxacin: (Moderate) Hyperglycemia and hypoglycemia have been reported in patients treated concomitantly with quinolones and antidiabetic agents. Therefore, careful monitoring of blood glucose is recommended when quinolones and antidiabetic agents are coadministered.
    Sulfonamides: (Moderate) Sulfonamides may enhance the hypoglycemic action of incretin mimetics and other antidiabetic agents. Sulfonamides may induce hypoglycemia in some patients by increasing the secretion of insulin from the pancreas. Patients at risk include those with compromised renal function, those fasting for prolonged periods, those that are malnourished, and those receiving high or excessive doses of sulfonamides. Patients should be closely monitored for this potential pharmacodynamic interaction while receiving any of these drugs in combination with incretin mimetics.
    Sympathomimetics: (Moderate) Sympathomimetics may increase blood glucose concentrations. Monitor for loss of diabetic control when therapy with sympathomimetic agents is instituted. Also, adrenergic medications may increase glucose uptake by muscle cells and may potentiate the actions of some antidiabetic agents. Monitor blood glucose to avoid hypoglycemia or hyperglycemia.
    Tacrolimus: (Moderate) Tacrolimus has been reported to cause hyperglycemia. Furthermore, tacrolimus has been implicated in causing insulin-dependent diabetes mellitus in patients after renal transplantation. The mechanism of hyperglycemia is thought to be through direct beta-cell toxicity. Patients should be monitored for worsening of glycemic control if therapy with tacrolimus is initiated in patients receiving antidiabetic agents, including incretin mimetics.
    Tegaserod: (Moderate) Tegaserod can enhance gastric emptying in patients with diabetes. Typically, blood glucose could be affected, which, in turn, may affect the clinical response to antidiabetic agents. However, incretin mimetics have been shown to slow gastric emptying. The clinical effects of these competing mechanisms is not known. The dosing of antidiabetic agents may require adjustment and blood glucose should be closely monitored when coadministered with tegaserod.
    Telmisartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.
    Testolactone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Testosterone: (Moderate) Exogenously administered androgens have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance, and may worsen hyperglycemia.However, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. Some patients may experience hypoglycemia. Other patients receiving androgen replacement may not have significant changes in blood glucose. Moniitor blood glucose and HbA1C in patients receiving antidiabetic agents and androgens. In some cases, dosage adjustments of the antidiabetic agent may be necessary.
    Thiazide diuretics: (Moderate) Thiazide diuretics can decrease insulin sensitivity thereby leading to glucose intolerance and hyperglycemia. Diuretic-induced hypokalemia may also lead to hyperglycemia. Because of this, a potential pharmacodynamic interaction exists between thiazide diuretics and antidiabetic agents. It appears that the effects of thiazide diuretics on glycemic control are dose-related and low doses can be instituted without deleterious effects on glycemic control. In addition, diuretics reduce the risk of stroke and cardiovascular disease in patients with diabetes. However, patients taking antidiabetic agents should be monitored for changes in blood glucose control if such diuretics are added or deleted. Dosage adjustments may be necessary. Finally, both thiazides and sulfonylureas have been reported to cause photosensitivity reactions; concomitant use may increase the risk of photosensitivity.
    Thiethylperazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Thioridazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Thyroid hormones: (Minor) Thyroid hormones are important in the regulation of carbohydrate metabolism, gluconeogenesis, the mobilization of glycogen stores, and protein synthesis. When thyroid hormones are added to existing diabetes therapy, the glucose-lowering effect may be reduced. Close monitoring of blood glucose is necessary for individuals who use antidiabetic agents whenever there is a change in thyroid treatment. It may be necessary to adjust the dose of antidiabetic agents if thyroid hormones are added or discontinued.
    Tipranavir: (Moderate) New onset diabetes mellitus, exacerbation of diabetes mellitus, and hyperglycemia due to insulin resistance have been reported with use of protease inhibitors. Patients taking antidiabetic agents should be closely monitored for changes in glycemic control, specifically hyperglycemia, if protease inhibitor therapy is initiated.
    Tobacco: (Minor) Monitor blood glucose concentrations for needed antidiabetic agent dosage adjustments in diabetic patients whenever a change in either nicotine intake or smoking status occurs. Nicotine activates neuroendocrine pathways (e.g., increases in circulating cortisol and catecholamine levels) and may increase plasma glucose. Tobacco smoking is known to aggravate insulin resistance. Cessation of nicotine therapy or tobacco smoking may result in a decrease in blood glucose.
    Trandolapril: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Trandolapril; Verapamil: (Moderate) ACE inhibitors may enhance the hypoglycemic effects of insulin or other antidiabetic agents by improving insulin sensitivity. Patients receiving these drugs concomitantly with antidiabetic agents should be monitored for changes in glycemic control.
    Tranylcypromine: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Triamterene: (Minor) Triamterene can decrease the hypoglycemic effects of antidiabetic agents, such as incretin mimetics, by producing an increase in blood glucose levels. Patients on antidiabetics should be monitored for changes in blood glucose control if triamterene is added or deleted. Dosage adjustments may be necessary.
    Trifluoperazine: (Minor) Phenothiazines have been reported to increase blood glucose concentrations. Use cautiously in patients receiving antidiabetic agents; patients should routinely monitor their blood glucose as indicated.
    Valsartan: (Moderate) Angiotensin II receptor antagonists may enhance the hypoglycemic effects of antidiabetic agents by improving insulin sensitivity. In addition, angiotensin II receptor antagonists have been associated with a reduced incidence in the development of new-onset diabetes in patients with hypertension or other cardiac disease. Patients receiving these drugs concomitantly should be monitored for changes in glycemic control.

    PREGNANCY AND LACTATION

    Pregnancy

    Liraglutide (Saxenda) for the treatment of obesity is contraindicated during pregnancy, because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm due to the potential hazard of maternal weight loss to the fetus. There are no adequate data or clinical studies of liraglutide (Victoza) use for the treatment of type 2 diabetes mellitus in pregnant women; use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the toxicities found in animal studies, it may be prudent to avoid liraglutide until data in human pregnancy are available. Rat studies have noted abnormalities and variations in the kidneys, and irregular skeletal ossification effects when liraglutide was given at or above 0.8 times the human systemic exposures, based on the maximum recommended human dose (MRHD) of 1.8 mg/day (determined from AUC). Reduced growth and increased total major abnormalities occurred in rabbits at systemic exposures below human exposure at the MRHD (determined from AUC). The American College of Obstetrician and Gynecologists recommends insulin as the therapy of choice to maintain blood glucose as close to normal as possible during pregnancy in patients with type 1 or 2 diabetes mellitus, and, if diet therapy alone is not successful, for those patients with gestational diabetes.

    In lactating rats, liraglutide was excreted unchanged in milk at concentrations approximately 50% of maternal plasma concentrations. Liraglutide excretion into human milk is unknown. Because many drugs are excreted in human milk and because of the potential for tumorigenicity shown for liraglutide in animal studies, a decision should be made whether to discontinue breast-feeding or to discontinue the drug, taking into account the importance of the drug to the mother. If liraglutide is discontinued and blood glucose is not controlled on diet and exercise alone, insulin therapy should be considered. Other oral hypoglycemics may be considered as possible alternatives during breast-feeding. Because acarbose has limited systemic absorption, which results in minimal maternal plasma concentrations, clinically significant exposure via breast milk is not expected. Also, while the manufacturers of metformin recommend against breast-feeding while taking the drug, data have shown that metformin is excreted into breast milk in small amounts and adverse effects on infant plasma glucose have not been reported in human studies. The American Academy of Pediatrics (AAP) regards tolbutamide as usually compatible with breast-feeding. Although other sulfonylureas have not been evaluated by the AAP, glyburide may be a suitable alternative since it was not detected in the breast milk of lactating women who received single and multiple doses of glyburide. If any oral hypoglycemics are used during breast feeding, the nursing infant should be monitored for signs of hypoglycemia, such as increased fussiness or somnolence.

    MECHANISM OF ACTION

    Liraglutide is an incretin mimetic; specifically, liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous GLP-1 (7—37). GLP-1 (7—37) represents < 20% of total circulating endogenous GLP-1. Liraglutide binds and activates the GLP-1 receptor. GLP-1 is an important, gut-derived, glucose homeostasis regulator that is released after the oral ingestion of carbohydrates or fats. In patients with type 2 diabetes, GLP-1 concentrations are decreased in response to an oral glucose load. GLP-1 enhances insulin secretion; it increases glucose-dependent insulin synthesis and in vivo secretion of insulin from pancreatic beta cells in the presence of elevated glucose. In addition to increases in insulin secretion and synthesis, GLP-1 suppresses glucagon secretion, slows gastric emptying, reduces food intake, and promotes beta-cell proliferation. Liraglutide does not increase insulin secretion or suppress glucagon secretion at normal or low glucose concentrations.
     
    GLP-1 is also a physiological regulator of appetite and caloric intake and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. Liraglutide acts to reduce body weight through decreased caloric intake; it does not increase 24-hour energy expenditure.

    PHARMACOKINETICS

    Liraglutide is given via subcutaneous administration. Liraglutide is more than 98% bound to plasma protein. After a single radioactive liraglutide dose was administered to healthy subjects, the major component in plasma was intact liraglutide for the initial 24 hours. The metabolism of liraglutide mirrors that of large proteins without a specific organ as a major route of elimination. Following a radioactive liraglutide dose, intact liraglutide was not detected in urine or feces; only a minor part of the administered dose was excreted as metabolites in the urine (6%) or feces (5%). The mean apparent clearance following subcutaneous injection of a single dose of liraglutide is approximately 0.9 to 1.4 L/hour. Liraglutide is resistant to dipeptidyl peptidase-IV (DDP-IV), the endogenous enzyme responsible for the degradation of GLP-1; this allows for a long half-life (13 hours) and once daily dosing.

    Intravenous Route

    The mean volume of distribution after IV administration is 0.07 L/kg.

    Subcutaneous Route

    Following subcutaneous injection, liraglutide binds to albumin at the injection site, and thereafter, is released slowly into circulation. Peak plasma concentrations are achieved in roughly 8 to 12 hours; after a 0.6 mg subcutaneous dose, mean peak concentration was 35 ng/mL and total area under the curve (AUC) was 960 ng x h/mL. Liraglutide Cmax and AUC increased proportionally over the therapeutic dose range of 0.6 to 1.8 mg. At a dose of 1.8 mg, the average steady state concentration over 24 hours was approximately 128 ng/mL. In obese patients (BMI 30 to 40 kg/m2), the average steady state concentration over 24 hours was approximately 116 ng/mL. Similar absorption is achieved with subcutaneous administration of liraglutide in the abdomen, thigh, or arm. The absolute bioavailability of liraglutide following subcutaneous injection is approximately 55%. The mean apparent volume of distribution following subcutaneous administration of 0.6 mg and 3 mg of liraglutide is approximately 13 liters and 20 to 25 liters, respectively. Liraglutide is resistant to dipeptidyl peptidase-IV (DDP-IV), the endogenous enzyme responsible for the degradation of GLP-1; this allows for a long half-life (12 to 13 hours) and once daily dosing.