Rybelsus

Glucagon-like Peptide-1 (GLP-1) Receptor Agonists
Glucagon-like Peptide-1 (GLP-1) Receptor Agonists for Obesity

Oral Administration Oral Solid Formulations

Administer the tablets at least 30 minutes before the first food, beverage, or other oral medications of the day with no more than 4 ounces of plain water. Waiting less than 30 minutes, or taking semaglutide with food, beverages (other than plain water) or other oral medications will reduce efficacy of semaglutide by decreasing its absorption. Waiting more than 30 minutes to eat may increase the absorption of semaglutide.
The patient should swallow tablets whole. Do not split, crush, or chew tablets.
Missed dose: If a dose is missed, the missed dose should be skipped, and the next dose should be taken the following day.

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.
Injection 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; reserve the use of any pen to 1 patient only.

Subcutaneous Administration

Ozempic Pen
General information
Ozempic Pen is available as a pre-filled "dial a dose" pen (0.25, 0.5, 1, and 2 mg). The pen should be used with NovoFine Plus or Novofine disposable needles up to a length of 8 mm. The pen comes with NovoFine Plus 32-gauge 4 mm disposable needles.
When used concomitantly with insulin therapy, administer as separate injections. Never mix them together. The two injections may be injected in the same body region, but the injections should not be adjacent to each other.
Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use of the pen should be supplied before a patient or caregiver administers a dose. Patients/caregivers should review the "Instructions for Use" in their pen package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
Administer every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
Missed dose: If a dose is missed, give as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and administer on the next scheduled day. The day of weekly administration can be changed if needed, as long as the time between 2 doses is at least 2 days (more than 48 hours).
Subcutaneous Pen Administration (Ozempic Pen)
Wash and dry hands before use.
Each semaglutide pen must be primed prior to the first use. See the pen user manual for priming directions.
Always attach a new needle right before each injection. Pull the pen cap off, but do not throw it away. Push the needle straight onto the pen. Turn until it is on tight. Pull off the inner needle cap and throw it away.
Turn the dose selector on the pen until the dose counter shows the dose. Double-check the dosage selected prior to administration.
Inject subcutaneously into the thigh, abdomen, or upper arm.
Press down in the center of the dose button to inject until the "0" lines up with the pointer. Inject over 6 seconds to ensure the full dose is injected. The patient may hear or feel a 'click'. Keep thumb on the injection button until the needle is removed from the skin. Remove the needle from the skin.
Remove and dispose of the used needle in an appropriate sharps container after each injection.
Place the pen cap back on the pen.
Rotate administration sites with each injection to prevent lipodystrophy.
Storage of opened pens: Do not store the "in-use" pen with the needle on; this will reduce the potential for contamination, infection, and leakage and will help ensure dosing accuracy. The open pen can be stored for 56 days below 86 degrees F (30 degrees C) or in a refrigerator at 36 to 46 degrees F (2 to 8 degrees C). Do not freeze. Throw away the pen after 56 days, even if it still has medication left in it.
 
Wegovy Pen
General information
Wegovy Pen is available in 5 pre-filled, disposable, single-dose pens (0.25, 0.5, 1, 1.7, and 2.4 mg). Ensure the correct dose of the pen is chosen for the dose to be administered.
Administer once every 7 days (once weekly) on the same day each week; the dose can be administered at any time of day, with or without meals.
Instruct patients/caregivers on proper injection technique. Adequate oral and written instructions on the use of the pen should be supplied before a patient or caregiver administers a dose. Patients/caregivers should review the "Instructions for Use" in their pen package. People who are blind or have vision problems should not use the pen without help from a person trained to use the pen.
Missed dose: If 1 dose is missed and the next scheduled dose is more than 2 days away (48 hours), administer dose as soon as possible. If 1 dose is missed and the next scheduled dose is less than 2 days away (48 hours), do not administer the dose. Resume dosing on the regularly scheduled day of the week. If more than 2 consecutive doses are missed, resume dosing as scheduled. Alternatively, if needed, restart the initial titration schedule, which may reduce the occurrence of gastrointestinal symptoms associated with reinitiating treatment.
Subcutaneous Pen Administration (Wegovy Pen)
Wash and dry hands before use.
The dose of semaglutide is already set on the Wegovy pen; each pen is for one-time use only.
The needle is covered by the needle cover and will not be seen. Do not remove the pen cap until ready to inject; do not touch or push the needle cover to avoid a needle stick injury.
Inject subcutaneously into the thigh, abdomen, or upper arm by pressing the needle cap firmly against the skin; this will begin the injection. Do not inject into an area where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks.
Do not remove the pen from the skin before the yellow bar in the pen window has stopped moving. The medication may appear on the skin or squirt from the needle and the full dose may not be received if the pen is removed too early or the pen is not pressed firmly against the skin for the entire injection. The needle cover will lock when it is removed from the skin. The injection cannot be stopped and restarted later.
If the yellow bar does not start moving or stops moving during the injection, advise the patient to contact their health care provider or Novo Nordisk at startWegovy.com or call Novo Nordisk Inc. at 1-833-934-6891.
Dispose of the used pen in an appropriate sharps container after each injection. Each Wegovy pen is for single-use only.
Rotate administration sites with each injection to prevent lipodystrophy.

Severe

retinopathy / Delayed / 0.7-4.2
cholecystitis / Delayed / 0.6-0.8
appendicitis / Delayed / 0.5-0.5
pancreatitis / Delayed / 0.1-0.3
ileus / Delayed / Incidence not known
renal failure / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
new primary malignancy / Delayed / Incidence not known

Moderate

constipation / Delayed / 3.1-24.0
hypoglycemia / Early / 1.0-11.0
gastritis / Delayed / 0.4-4.0
cholelithiasis / Delayed / 0.4-3.8
elevated hepatic enzymes / Delayed / 3.0-3.0
antibody formation / Delayed / 0.5-3.0
hypotension / Rapid / 1.3-2.3
dehydration / Delayed / Incidence not known
hyperamylasemia / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known

Mild

nausea / Early / 11.0-44.0
vomiting / Early / 5.0-36.0
diarrhea / Early / 8.5-30.0
abdominal pain / Early / 5.7-20.0
headache / Early / 14.0-17.0
pharyngitis / Delayed / 12.0-12.0
fatigue / Early / 0.4-11.0
dyspepsia / Early / 0.6-9.0
dizziness / Early / 0.4-8.0
eructation / Early / 0.6-7.0
flatulence / Early / 0.4-6.0
gastroesophageal reflux / Delayed / 1.5-5.0
anxiety / Delayed / 4.0-4.0
alopecia / Delayed / 3.0-4.0
sinusitis / Delayed / 4.0-4.0
infection / Delayed / 4.0-4.0
rash / Early / 3.0-3.0
urticaria / Rapid / 3.0-3.0
influenza / Delayed / 3.0-3.0
injection site reaction / Rapid / 0.2-1.4
syncope / Early / 0.8-0.8
dysgeusia / Early / 0.4

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

Semaglutide is contraindicated in patients with a personal or family history of certain types of thyroid cancer, specifically thyroid C-cell tumors such as medullary thyroid carcinoma (MTC), or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Semaglutide 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 semaglutide at all dose levels (greater than 2X human exposure). It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans. Cases of MTC in patients treated with liraglutide, another GLP-1 receptor agonist, have been reported in the postmarketing period; the data in these reports are insufficient to establish or exclude a causal relationship between MTC and GLP-1 receptor agonist 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 semaglutide, if serum calcitonin is measured and found to be elevated, the patient should be referred to an endocrinologist for further evaluation.

OZEMPIC, Rybelsus, Wegovy

Rx

Incretin mimetic (GLP-1 receptor agonist); available as a once-weekly subcutaneous injection or as an oral tablet given once daily
Ozempic (injection) and Rybelsus (oral) product used to improve glycemic control in adults with type 2 diabetes mellitus (DM); injection also indicated to reduce the risk of non-fatal and fatal cardiovascular events (e.g., MI or stroke) if T2DM patient also has CV disease
Separate product (Wegovy injection) used for weight reduction and maintenance for obese or overweight adults with at least 1 weight-related comorbidity and for pediatric patients aged 12 years and older with an initial BMI at the 95th percentile or greater

For the treatment of type 2 diabetes mellitus as an adjunct to diet and exercise. Oral dosage (semaglutide-naive) (e.g., Rybelsus) Adults

3 mg PO once daily for 30 days, then 7 mg PO once daily, initially. May increase the dose to 14 mg PO once daily after at least 30 days on 7 mg/day if additional glycemic control is needed. Administering two 7 mg tablets to achieve a 14 mg dose is not recommended.

Oral dosage (converting from semaglutide injection) (e.g., Rybelsus) Adults

7 or 14 mg PO once daily for 0.5 mg subcutaneously once weekly starting up to 7 days after the last injection. There is no equivalent oral dose for a 1 mg subcutaneous dose.

Subcutaneous dosage (semaglutide-naive) (e.g., Ozempic) Adults

0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg subcutaneously once weekly, initially. May increase the dose to 1 mg subcutaneously once weekly after 4 weeks on 0.5 mg/week and 2 mg subcutaneously once weekly after 4 weeks on 1 mg/week if additional glycemic control is needed.

Subcutaneous dosage (converting from semaglutide tablets) (e.g., Ozempic) Adults

0.5 mg subcutaneously once weekly for 14 mg PO once daily starting the day after the last oral dose. There is no equivalent oral dose for a 1 mg subcutaneous dose.

For the reduction of cardiovascular mortality, non-fatal myocardial infarction, or non-fatal stroke in persons with type 2 diabetes mellitus and established cardiovascular disease. Subcutaneous dosage (e.g., Ozempic) Adults

0.25 mg subcutaneously once weekly for 4 weeks, then 0.5 mg subcutaneously once weekly, initially. May increase the dose to 1 mg subcutaneously once weekly after 4 weeks on 0.5 mg/week and 2 mg subcutaneously once weekly after 4 weeks on 1 mg/week if additional glycemic control is needed.

For the treatment of obesity and for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity.
NOTE: Semaglutide is indicated in adults with an initial body mass index (BMI) of 30 kg/m2 or more or 27 kg/m2 or more in the presence of other risk factors (e.g., hypertension, type 2 diabetes, or dyslipidemia) and pediatric patients age 12 years and older with an initial BMI at the 95th percentile or more for age and sex.
Subcutaneous dosage (e.g., Wegovy) Adults

0.25 mg subcutaneously once weekly for weeks 1 through 4, then 0.5 mg subcutaneously once weekly for weeks 5 through 8, then 1 mg subcutaneously once weekly for weeks 9 through 12, then 1.7 mg subcutaneously once weekly for weeks 13 through 16, and then 2.4 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. May temporarily decrease dose to 1.7 mg subcutaneously once weekly for a maximum of 4 weeks if the 2.4 mg dose is not tolerated; resume 2.4 mg subcutaneously once weekly after 4 weeks. Discontinue use if the 2.4 mg dose is not tolerated.

Children and Adolescents 12 to 17 years

0.25 mg subcutaneously once weekly for weeks 1 through 4, then 0.5 mg subcutaneously once weekly for weeks 5 through 8, then 1 mg subcutaneously once weekly for weeks 9 through 12, then 1.7 mg subcutaneously once weekly for weeks 13 through 16, and then 2.4 mg subcutaneously once weekly. Consider delaying dose escalation for 4 weeks if a dose increase is not tolerated. May decrease dose to 1.7 mg subcutaneously once weekly if the 2.4 mg dose is not tolerated. Discontinue use if the 1.7 mg dose is not tolerated.

Hepatic Impairment

No dosage adjustments are needed.

Renal Impairment

No dosage adjustments are needed.

Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Acetaminophen; Aspirin: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amlodipine; Benazepril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amlodipine; Olmesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amlodipine; Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended.
Androgens: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Angiotensin II receptor antagonists: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Angiotensin-converting enzyme inhibitors: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Caffeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Carisoprodol: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Dipyridamole: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Omeprazole: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Aspirin, ASA; Oxycodone: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
atypical antipsychotic: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. 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.
Azilsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Azilsartan; Chlorthalidone: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Benazepril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Beta-blockers: (Moderate) Increased frequency of blood glucose monitoring may be required when a beta blocker is given with antidiabetic agents. Since beta blockers inhibit the release of catecholamines, these medications may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Beta-blockers also 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 noted to potentiate insulin-induced hypoglycemia and a delay in recovery of blood glucose to normal levels. Hyperglycemia has been reported as well and is possibly due to beta-2 receptor blockade in the beta cells of the pancreas. A selective beta-blocker may be preferred in patients with diabetes mellitus, if appropriate for the patient's condition. Selective beta-blockers, such as atenolol or metoprolol, do not appear to potentiate insulin-induced hypoglycemia. While beta-blockers may have negative effects on glycemic control, they reduce the risk of cardiovascular disease and stroke in patients with diabetes and their use should not be avoided in patients with compelling indications for beta-blocker therapy when no other contraindications are present.
Bismuth Subsalicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Bortezomib: (Moderate) During clinical trials of bortezomib, hypoglycemia and hyperglycemia were reported in diabetic patients receiving antidiabetic agents. Patients taking antidiabetic agents and receiving bortezomib treatment may require close monitoring of their blood glucose levels and dosage adjustment of their medication.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Captopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Carbamazepine: (Moderate) Consider increased clinical or laboratory monitoring for carbamazepine if administered with oral semaglutide as the oral absorption of carbamazepine may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide.
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, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Chlorpropamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Chlorthalidone; Clonidine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Choline Salicylate; Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended.
Clonidine: (Minor) Increased frequency of blood glucose monitoring may be required when clonidine is given with antidiabetic agents. Since clonidine inhibits the release of catecholamines, clonidine may hide symptoms of hypoglycemia such as tremor, tachycardia, and blood pressure changes. Other symptoms, like headache, dizziness, nervousness, mood changes, or hunger are not blunted. Clonidine does not appear to impair recovery from hypoglycemia, and has not been found to impair glucose tolerance in diabetic patients.
Codeine; Phenylephrine; Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Codeine; Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Corticosteroids: (Moderate) Monitor blood glucose during concomitant corticosteroid and incretin mimetic use; an incretin mimetic dose adjustment may be necessary. Corticosteroids may increase blood glucose concentrations. Risk factors for impaired glucose tolerance due to corticosteroids include the corticosteroid dose and duration of treatment. Corticosteroids stimulate hepatic glucose production and inhibit peripheral glucose uptake into muscle and fatty tissues, producing insulin resistance. Decreased insulin production may occur in the pancreas due to a direct effect on pancreatic beta cells.
Cyclosporine: (Moderate) Consider increased clinical or laboratory monitoring for oral cyclosporine administered with oral semaglutide as the absorption of cyclosporine may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV cyclosporine. Patients should also be monitored for worsening of glycemic control when any form of systemic cyclosporine is initiated in patients receiving antidiabetic agents, including semaglutide. Cyclosporine has been reported to cause hyperglycemia. Cyclosporine may have direct beta-cell toxicity and the effects may be dose-related.
Daclatasvir: (Moderate) Closely monitor blood glucose levels if daclatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as daclatasvir.
Danazol: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
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.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (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.
Diazoxide: (Minor) Diazoxide, when administered intravenously or orally, produces a prompt dose-related increase in blood glucose level, due primarily to an inhibition of insulin release from the pancreas, and also to an extrapancreatic effect. The hyperglycemic effect begins within an hour and generally lasts no more than 8 hours in the presence of normal renal function. The hyperglycemic effect of diazoxide is expected to be antagonized by certain antidiabetic agents (e.g., insulin or a sulfonylurea). Blood glucose should be closely monitored.
Digoxin: (Moderate) Consider increased clinical or laboratory monitoring for digoxin if administered with oral semaglutide as the oal absorption of digoxin may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide or IV digoxin.
Disopyramide: (Moderate) Disopyramide may enhance the hypoglycemic effects of antidiabetic agents. Patients receiving this combination should be monitored for changes in glycemic control.
Elbasvir; Grazoprevir: (Moderate) Closely monitor blood glucose levels if elbasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as elbasvir.
Enalapril, Enalaprilat: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Eprosartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Esterified Estrogens; Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Ethotoin: (Minor) Ethotoin 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.
Fibric acid derivatives: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fibric acid derivative use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fluoxetine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fluoxetine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fluphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Fosphenytoin: (Minor) Fosphenytoin 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) Patients receiving antidiabetic agents should use dietary supplements of Garlic, Allium sativum with caution. Constituents in garlic might have some antidiabetic activity, and may increase serum insulin levels and increase glycogen storage in the liver. Monitor blood glucose and glycemic control. Patients with diabetes should inform their health care professionals of their intent to ingest garlic dietary supplements. Some patients may require adjustment to their hypoglycemic medications over time. One study stated that additional garlic supplementation (0.05 to 1.5 grams PO per day) contributed to improved blood glucose control in patients with type 2 diabetes mellitus within 1 to 2 weeks, and had positive effects on total cholesterol and high/low density lipoprotein regulation over time. It is unclear if hemoglobin A1C is improved or if improvements are sustained with continued treatment beyond 24 weeks. Other reviews suggest that garlic may provide modest improvements in blood lipids, but few studies demonstrate decreases in blood glucose in diabetic and non-diabetic patients. More controlled trials are needed to discern if garlic has an effect on blood glucose in patients with diabetes. When garlic is used in foods or as a seasoning, or at doses of 50 mg/day or less, it is unlikely that blood glucose levels are affected to any clinically significant degree.
Glecaprevir; Pibrentasvir: (Moderate) Closely monitor blood glucose levels if glecaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as glecaprevir. (Moderate) Closely monitor blood glucose levels if pibrentasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as pibrentasvir.
Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of 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.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Hydroxychloroquine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and hydroxychloroquine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Hydroxyprogesterone: (Minor) Progestins, like hydroxyprogesterone, can impair glucose tolerance. Patients receiving antidiabetic agents should be closely monitored for signs indicating changes in diabetic control when therapy with progestins is instituted or discontinued.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant insulin aspart and semaglutide use; consider decreasing the insulin aspart dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant insulin degludec and semaglutide use; consider decreasing the insulin degludec dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant insulin degludec and semaglutide use; consider decreasing the insulin degludec dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant insulin detemir and semaglutide use; consider decreasing the insulin detemir dose when starting semaglutide. The recommended starting dose of insulin detemir is 10 units/day in persons with type 2 diabetes mellitus inadequately controlled with a glucagon-like peptide-1 (GLP-1) receptor agonist. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant insulin glargine and semaglutide use; consider decreasing the insulin glargine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant insulin glargine and semaglutide use; consider decreasing the insulin glargine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant insulin glulisine and semaglutide use; consider decreasing the insulin glulisine dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant insulin lispro and semaglutide use; consider decreasing the insulin lispro dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin Regular: (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant insulin and semaglutide use; consider decreasing the insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Irbesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Isocarboxazid: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lanreotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended.
Ledipasvir; Sofosbuvir: (Moderate) Closely monitor blood glucose levels if ledipasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agent(s) may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as ledipasvir. (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir.
Levothyroxine: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
Levothyroxine; Liothyronine (Porcine): (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
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: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
Lisinopril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Lonapegsomatropin: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Magnesium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Mecasermin, Recombinant, rh-IGF-1: (Moderate) Use caution in combining mecasermin, recombinant, rh-IGF-1 or mecasermin rinfabate (rh-IGF-1/rh-IGFBP-3) with antidiabetic agents. 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. An increased risk for hypoglycemia is possible. The hypoglycemic effect induced by IGF-1 activity may be exacerbated. 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 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.
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.
Methenamine; Sodium Salicylate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Methyltestosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Monoamine oxidase inhibitors: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Nebivolol; Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
Niacin; Simvastatin: (Moderate) Niacin (nicotinic acid) interferes with glucose metabolism and can result in hyperglycemia. Changes in glycemic control can usually be corrected through modification of hypoglycemic therapy. Monitor patients taking antidiabetic agents for changes in glycemic control if niacin (nicotinic acid) is added or deleted to the medication regimen. Dosage adjustments may be necessary.
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.
Nirmatrelvir; 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.
Octreotide: (Moderate) Monitor patients receiving octreotide concomitantly with insulin or other antidiabetic agents for changes in glycemic control and adjust doses of these medications accordingly. Octreotide alters the balance between the counter-regulatory hormones of insulin, glucagon, and growth hormone, which may result in hypoglycemia or hyperglycemia. The hypoglycemia or hyperglycemia which occurs during octreotide acetate therapy is usually mild but may result in overt diabetes mellitus or necessitate dose changes in insulin or other hypoglycemic agents. In patients with concomitant type1 diabetes mellitus, octreotide is likely to affect glucose regulation, and insulin requirements may be reduced. Symptomatic hypoglycemia, which may be severe, has been reported in type 1 diabetic patients. In Type 2 diabetes patients with partially intact insulin reserves, octreotide administration may result in decreases in plasma insulin levels and hyperglycemia.
Olanzapine; Fluoxetine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and fluoxetine use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Olmesartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Orlistat: (Minor) Weight-loss may affect glycemic control in patients with diabetes mellitus. In many patients, glycemic control may improve. A reduction in dose of oral hypoglycemic medications may be required in some patients taking orlistat. Monitor blood glucose and glycemic control and adjust therapy as clinically indicated.
Oxandrolone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Oxymetholone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Pasireotide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pasireotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pasireotide inhibits the secretion of insulin and glucagon. Patients treated with pasireotide may experience either hypoglycemia or hyperglycemia.
Pegvisomant: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when pegvisomant treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Pegvisomant increases sensitivity to insulin by lowering the activity of growth hormone, and in some patients glucose tolerance improves with treatment. Patients with diabetes treated with pegvisomant and antidiabetic agents may be more likely to experience hypoglycemia.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Perindopril; Amlodipine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Perphenazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Perphenazine; Amitriptyline: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Phenelzine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Phenothiazines: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Phenytoin: (Moderate) Consider increased clinical or laboratory monitoring for oral phenytoin administered with oral semaglutide as the absorption of phenytoin may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV phenytoin. Patients should also be monitored for worsening of glycemic control when any form of systemic phenytoin is initiated in patients receiving antidiabetic agents, including semaglutide. Phenytoin has been reported to cause hyperglycemia.
Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Prochlorperazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Promethazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Promethazine; Dextromethorphan: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Promethazine; Phenylephrine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Quinolones: (Moderate) Monitor blood glucose during concomitant incretin mimetic and quinolone use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Ramipril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant insulin NPH and semaglutide use; consider decreasing the insulin NPH dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia. (Moderate) Monitor blood glucose during concomitant regular insulin and semaglutide use; consider decreasing the regular insulin dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Salicylates: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Salsalate: (Moderate) Monitor blood glucose during concomitant incretin mimetic and salicylate use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Sofosbuvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir.
Sofosbuvir; Velpatasvir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct

acting antivirals, such as sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Closely monitor blood glucose levels if sofosbuvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as sofosbuvir. (Moderate) Closely monitor blood glucose levels if velpatasvir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as velpatasvir. (Moderate) Closely monitor blood glucose levels if voxilaprevir is administered with antidiabetic agents. Dose adjustments of the antidiabetic agents may be needed. Altered blood glucose control, resulting in serious symptomatic hypoglycemia, has been reported in diabetic patients receiving antidiabetic agents in combination with direct acting antivirals, such as voxilaprevir.
Somapacitan: (Moderate) Patients with diabetes mellitus should be monitored closely during somapacitan therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somapacitan therapy is instituted in these patients. Growth hormones, such as somapacitan, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somapacitan, especially in those with risk factors for diabetes mellitus.
Somatrogon: (Moderate) Monitor for loss of glycemic control if concomitant use of somatrogon and antidiabetic drugs is necessary; a dose adjustment of the antidiabetic drug may be needed. Growth hormones, such as somatrogon, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control.
Somatropin, rh-GH: (Moderate) Patients with diabetes mellitus should be monitored closely during somatropin (recombinant rhGH) therapy. Antidiabetic drugs (e.g., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. Growth hormones, such as somatropin, may decrease insulin sensitivity, leading to glucose intolerance and loss of blood glucose control. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus.
Sulfonamides: (Moderate) Monitor blood glucose during concomitant incretin mimetic and sulfonamide use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Sympathomimetics: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. Sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes.
Tacrolimus: (Moderate) Consider increased clinical or laboratory monitoring for oral tacrolimus administered with oral semaglutide as the absorption of tacrolimus may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This absorption interaction does not occur with subcutaneous semaglutide or IV tacrolimus. Patients should also be monitored for worsening of glycemic control when any form of systemic tacrolimus is initiated in patients receiving antidiabetic agents, including semaglutide. Tacrolimus has been reported to cause hyperglycemia. The mechanism of hyperglycemia is thought to be through direct beta-cell toxicity.
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) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Telmisartan; Amlodipine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Testosterone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Theophylline, Aminophylline: (Moderate) Consider increased clinical or laboratory monitoring for aminophylline if administered with oral semaglutide as the absorption of aminophylline may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index, such as aminophylline, a prodrug for theophylline. Administer oral semaglutide separately from other oral medications. Monitor theophylline levels as clinically indicated. This interaction does not occur with subcutaneous semaglutide or with IV aminophylline. (Moderate) Consider increased clinical or laboratory monitoring for theophylline if administered with oral semaglutide as the absorption of theophylline may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications, particularly those with a narrow therapeutic index, such as theophylline. Administer oral semaglutide separately from other oral medications. Monitor theophylline levels as clinically indicated. This interaction does not occur with subcutaneous semaglutide or with IV theophylline.
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.
Thioridazine: (Minor) Phenothiazines, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Thyroid hormones: (Moderate) Consider additional thyroid function monitoring during concomitant use of oral thyroid hormones and oral semaglutide. Advise patients to take oral semaglutide 30 minutes before other oral medications. Concomitant use has been observed to increase levothyroxine exposure by 33% which may increase the risk for symptoms of hyperthyroidism or require a dosage adjustment. Semaglutide delays gastric emptying which may affect the absorption of other orally administered medications. This absorption interaction is not expected with subcutaneous semaglutide or intravenous levothyroxine. Additionally, levothyroxine may worsen glycemic control in patients with diabetes.
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.
Tolazamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tolbutamide: (Moderate) Monitor blood glucose during concomitant sulfonylurea and semaglutide use; consider decreasing the sulfonylurea dose when starting semaglutide. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Trandolapril: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Trandolapril; Verapamil: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin-converting enzyme (ACE) inhibitor use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Tranylcypromine: (Moderate) Monitor blood glucose during concomitant incretin mimetic and monoamine oxidase inhibitor (MAOI) use; an incretin mimetic dose adjustment may be necessary. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
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.
Triamterene; Hydrochlorothiazide, HCTZ: (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, especially chlorpromazine, may increase blood glucose concentrations. Hyperglycemia and glycosuria have been reported. Patients who are taking antidiabetic agents should monitor for worsening glycemic control when a phenothiazine is instituted.
Valsartan: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood glucose during concomitant incretin mimetic and angiotensin receptor blocker use. Concomitant use may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) The concomitant use of clarithromycin and antidiabetic agents can result in significant hypoglycemia. Careful monitoring of blood glucose is recommended.
Warfarin: (Moderate) Consider additional warfarin monitoring during concomitant use of oral semaglutide. Oral semaglutide delays gastric emptying and has been observed to increase warfarin overall exposure. Advise patients to take oral semaglutide 30 minutes before other oral medications. This interaction is not expected with subcutaneous semaglutide.

OZEMPIC/Wegovy Subcutaneous Inj Sol: 0.25mg, 0.5mg, 0.5mL, 0.68mg, 0.75mL, 1mL, 1mg, 1.34mg, 1.7mg, 2.4mg, 2.68mg
Rybelsus Oral Tab: 3mg, 7mg, 14mg

Adults

2 mg/week subcutaneously for the treatment of type 2 diabetes mellitus; 2.4 mg/week subcutaneously for the treatment of obesity; 14 mg/day PO for the treatment of type 2 diabetes mellitus.

Geriatric

2 mg/week subcutaneously for the treatment of type 2 diabetes mellitus; 2.4 mg/week subcutaneously for the treatment of obesity; 14 mg/day PO for the treatment of type 2 diabetes mellitus.

Adolescents

2.4 mg/week subcutaneously for the treatment of obesity; safety and efficacy have not been established for the treatment of type 2 diabetes mellitus.

Children

12 years: 2.4 mg/week subcutaneously for the treatment of obesity; safety and efficacy have not been established for the treatment of type 2 diabetes mellitus.
1 to 11 years: Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Semaglutide an incretin mimetic; specifically, semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist with 94% sequence homology to human GLP-1. Semaglutide 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. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation; semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Therefore, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Semaglutide is given via subcutaneous or oral administration. The mean estimated volume of distribution is 12.5 L and 8 L following subcutaneous and oral administration; respectively. Semaglutide is more than 99% bound to plasma albumin. The primary route of elimination is metabolism following proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid side-chain. The primary excretion routes of semaglutide-related material is via the urine and feces. Approximately 3% of the dose is excreted in the urine as intact semaglutide. The clearance is approximately 0.05 L/hour and 0.04 L/hour following subcutaneous and oral administration; respectively. With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose and up to 7 weeks after the last dose for the treatment of obesity.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

Oral Route

Semaglutide is co-formulated with salcaprozate sodium which facilitates the absorption of semaglutide after oral administration. The absorption of semaglutide primarily occurs in the stomach. Population pharmacokinetics (PK) estimated semaglutide exposure to increase in a dose-proportional manner. The mean population-PK estimated steady-state concentrations following once daily oral administration of 7 and 14 mg were approximately 6.7 nmol/L and 14.6 nmol/L, respectively. Following oral administration, maximum concentration of semaglutide is reached 1 hour post-dose. Steady-state exposure is achieved following 4 to 5 weeks administration. Population-PK estimated absolute bioavailability of semaglutide is approximately 0.4% to 1%, following oral administration.
 
Oral semaglutide tablets are formulated with salcaprozate sodium (SNAC), an absorption enhancer. UGT2B7 is an enzyme involved in SNAC clearance. SNAC crosses the placenta and reaches fetal tissues in rats and SNAC and/or its metabolites concentrated in the milk of lactating rats.

Subcutaneous Route

Following subcutaneous administration, maximum concentrations of semaglutide were attained at 1 to 3 days post-dosing. Similar exposure is achieved with subcutaneous administration of semaglutide in the abdomen, thigh, or upper arm. The absolute bioavailability of subcutaneous semaglutide is 89%.
Ozempic: The mean population estimated steady-state concentrations following once weekly subcutaneous administration of 0.5 mg and 1 mg semaglutide were approximately 65 ng/mL and 123 ng/mL, respectively. Steady-state exposures are achieved following 4 to 5 weeks of once-weekly administration. Exposures at the 0.5 mg and 1 mg dose levels were consistent with a dose-proportional increase. In the trial comparing semaglutide 1 mg and 2 mg, the mean steady state concentrations were 111.1 ng/mL and 222.1 ng/mL, respectively.
Wegovy: The average semaglutide steady-state concentration following subcutaneous administration of semaglutide was approximately 75 nmol/L in patients with either obesity (BMI greater than or equal to 30 kg/m2) or overweight (BMI 27 kg/m2 or more). The steady-state exposure of semaglutide increased proportionally with doses up to 2.4 mg subcutaneously once weekly.

Pregnancy

Semaglutide (Wegovy) for the treatment of obesity or weight management should not be used 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 is a pregnancy exposure registry for women who use semaglutide intended for weight management (Wegovy) during pregnancy. Contact Novo Nordisk at 1-800-727-6500 for more information. According to the American Association of Clinical Endocrinologists the and American College of Endocrinology (AACE/ACE) Obesity Clinical Practice Guidelines, weight loss medications must not be used during pregnancy; these guidelines recommend contraception requirements for patients of childbearing potential; those receiving semaglutide for weight reduction should use adequate contraception and discontinue semaglutide if pregnancy occurs. There are no adequate data or clinical studies of semaglutide use for the treatment of type 2 diabetes mellitus (T2DM) in pregnant women to inform a drug-associated risk for adverse developmental outcomes; use in pregnancy only if the potential benefit justifies the potential risk to the fetus. Rat studies have noted embryofetal mortality, structural abnormalities, and alterations to growth at maternal exposures below the maximum recommended human dose (MRHD) based on exposure AUC. In rabbits and cynomolgus monkeys administered semaglutide during organogenesis, early pregnancy losses and structural abnormalities were observed at below the MRHD (rabbit) and 5-fold or greater the MRHD (monkey). Poorly controlled diabetes during pregnancy also increases fetal risk.[62656] [64637] In addition, salcaprozate sodium (SNAC), an absorption enhancer in oral semaglutide tablets, crosses the placenta, and reaches fetal tissues in rats. In a pre- and postnatal development study of SNAC exposure, an increase in gestation length, an increase in the number of stillbirths, and a decrease in pup viability were observed.[64637] The American College of Obstetricians and Gynecologists (ACOG) and the American Diabetes Association (ADA) continue to recommend human insulin as the standard of care in pregnant women with diabetes mellitus and gestational diabetes mellitus (GDM) requiring medical therapy; insulin does not cross the placenta.[64926] [62358] [62656] [64637]

Use injectable semaglutide with caution during lactation; oral semaglutide therapy is not recommended during breast-feeding. There are no data on the presence of semaglutide in human milk, the effects on the breast-fed infant, or the effects on milk production. Semaglutide was present in the milk of lactating rats and was detected at levels 3- to 12- fold lower than in maternal rat plasma.  Salcaprozate sodium (SNAC) (an absorption enhancer in oral semaglutide tablets) and/or its metabolites concentrated in the milk of lactating rats. There are no data on the presence of SNAC in human milk. Since the activity of UGT2B7, an enzyme involved in SNAC clearance, is lower in infants compared to adults, higher SNAC plasma levels may occur in neonates and infants. Because of the unknown potential for serious adverse reactions in the breastfed infant due to the possible accumulation of SNAC from breast-feeding and because semaglutide injection can be considered for use during lactation, advise patients that breast-feeding is not recommended during treatment with oral semaglutide tablets. If semaglutide 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. Tolbutamide is usually considered compatible with breast-feeding. Glyburide may also 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.