Skip to Content

Semaglutide

Class: Incretin Mimetics
Molecular Formula: C187H291N45O59
CAS Number: 910463-68-2
Brands: Ozempic, Rybelsus

Medically reviewed by Drugs.com. Last updated on Oct 12, 2020.

Warning

    Risk of Thyroid C-Cell Tumors
  • Causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice.1 24 25

  • Unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans, as relevance to humans of such tumors in rodents has not been determined.1 24

  • Contraindicated in patients with a personal or family history of MTC and in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2).1 2 24

    Counsel patients regarding potential risk of MTC and inform them about symptoms of thyroid tumors.1 2 24 25 (See Advice to Patients.)

    Routine monitoring of serum calcitonin or use of thyroid ultrasound of uncertain value for early detection of MTC in patients receiving semaglutide.1 24

Introduction

Antidiabetic agent; glucagon-like peptide-1 (GLP-1) agonist (incretin mimetic).1 15 17 24

Uses for Semaglutide

Type 2 Diabetes Mellitus

Glycemic Control

Used orally and by sub-Q injection as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.1 4 5 6 7 8 9 14 23 24

Has been used alone or in combination with one or more antidiabetic agents (e.g., metformin, a sulfonylurea, a thiazolidinedione, a dipeptidyl peptidase [DPP]-4 inhibitor, a sodium-glucose cotransporter 2 [SGLT2] inhibitor, basal insulin) as an adjunct to diet and exercise for the management of type 2 diabetes mellitus.1 4 5 6 7 8 14 23 24 26 27 28 29 32 33 34 35 36

As add-on therapy, generally has improved glycemic control and reduced body weight compared with add-on therapy with sitagliptin,1 5 24 28 32 empagliflozin,24 27 extended-release exenatide,1 6 36 liraglutide,24 29 34 36 dulaglutide,23 35 36 or insulin glargine.1 7 14

Current guidelines for the treatment of type 2 diabetes mellitus generally recommend metformin as first-line therapy in addition to lifestyle modifications due to its well-established safety and efficacy (i.e., beneficial effects on HbA1c, weight, and cardiovascular mortality).698 704 705

Consider patient's comorbidities (e.g., ASCVD, established renal disease, heart failure), hypoglycemia risk, impact on weight, cost, risk of adverse effects, and patient preferences when selecting additional antidiabetic agents (e.g., glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose cotransporter 2 [SGLT2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, thiazolidinedione, basal insulin) for patients with inadequate glycemic control on metformin monotherapy.698 704 705 706

Consider early initiation of combination therapy for the treatment of type 2 diabetes mellitus to extend the time to treatment failure and more rapidly attain glycemic goals.704

Experts recommend that patients with type 2 diabetes mellitus who have established (or a high risk for) ASCVD or heart failure receive a GLP-1 receptor agonist or SGLT2 inhibitor with demonstrated cardiovascular disease benefit.704 705

In patients with type 2 diabetes mellitus and CKD, consider a GLP-1 receptor agonist or SGLT2 inhibitor shown to reduce the risk of CKD progression, cardiovascular events, or both, in addition to metformin therapy or in those in whom metformin cannot be used.704 705 706

In patients on metformin monotherapy without established ASCVD or indicators of high ASCVD risk, heart failure, or CKD, base decision regarding the addition of other antidiabetic agents (e.g., GLP-1 receptor agonist, SGLT2 inhibitor, DPP-4 inhibitor, thiazolidinedione, sulfonylurea, basal insulin) to metformin therapy on avoidance of adverse effects, cost, and individual patient factors.704

Manufacturer of oral semaglutide (Rybelsus) recommends against use as first-line therapy for patients with inadequate glycemic control on diet and exercise.24 (See Risk of Thyroid C-Cell Tumors under Cautions.)

Not indicated for type 1 diabetes mellitus or diabetic ketoacidosis.1 24

Reduction in Risk of Cardiovascular Events

Used by sub-Q injection to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease.1 9 11 14 704 705 Semaglutide noninferior or superior to placebo with regard to primary outcome (first occurrence of cardiovascular death, nonfatal MI, nonfatal stroke) in clinical trials in such patients.9 14 31 80 81

Oral semaglutide also shown noninferior to placebo in terms of major adverse cardiovascular event outcomes.24 31 Some data suggest that cardiovascular benefits of semaglutide may be independent of route of administration.9 31 37

Beneficial Effects on Renal Function

Reduced risk of new or worsening nephropathy observed with use of some GLP-1 receptor agonists (e.g., liraglutide, semaglutide) in patients with type 2 diabetes mellitus at high risk for, or with existing, cardiovascular disease.9 81 706

Semaglutide Dosage and Administration

General

Perform regular monitoring (e.g., blood glucose determinations, HbA1c) to determine therapeutic response in patients with type 2 diabetes mellitus.1 2 24 25

Administration

Oral Administration

Instruct patients to take tablets at least 30 minutes before the first food, beverage, or other oral drugs of the day; take dose with no more than 120 mL of plain water only.24 25

Taking dose with or <30 minutes before food, beverages (other than plain water), or other oral drugs will lessen semaglutide's effects.24 25 Waiting more than 30 minutes to eat after taking the dose may increase drug absorption.24

Swallow tablets whole; do not cut, crush, or chew.24

If an oral dose is missed, omit the missed dose and take the next dose the following day.24

Sub-Q Administration

Administer by sub-Q injection into abdomen, thigh, or upper arm using a prefilled, single-use injection pen.1 2

Administer once daily at any time of day without regard to meals.1

If a sub-Q dose is missed, take the dose as soon as possible within 5 days after the missed dose.1 2 If >5 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.1 2 In each case, patients may resume their regular once-weekly dosing schedule.1 2 (See Dosage under Dosage and Administration.)

Administer semaglutide and insulin as separate injections in patients receiving both drugs for diabetes mellitus; do not mix insulin and semaglutide.1 2 May inject semaglutide and insulin in the same body region; however, do not administer injections adjacent to each other.1 2

Dosage

Adults

Type 2 Diabetes Mellitus
Glycemic Control
Oral

Initially, 3 mg once daily for 30 days.24 26 27 28 33 34 The 3-mg daily dosage is not effective for glycemic control; intended only as a starting dose to reduce GI intolerance.24

After 30 days, increase dosage to 7 mg once daily.24 27 28 33 34

After an additional 30 days or more, if needed, increase dosage to 14 mg once daily.24 27 28 33 34

Manufacturer states that taking two 7-mg tablets to achieve a 14-mg dose not recommended.24

Switching from oral to sub-Q dosing: Patients taking 14 mg orally once daily may switch to 0.5 mg sub-Q once weekly; start sub-Q dosage the day after the last oral dose.24

Glycemic Control and Reduction in Risk of Cardiovascular Events
Sub-Q

Initially, 0.25 mg once weekly for 4 weeks.1 10 11 The 0.25 mg once-weekly dosage is not effective for glycemic control; intended only as a starting dose to reduce GI intolerance.1 10 15

After 4 weeks, increase dosage to 0.5 mg once weekly.1 10 11 After an additional 4 weeks or more, if needed, may increase dosage to 1 mg once weekly.1 10 11

Switching from sub-Q to oral dosing: Patients taking 0.5 mg sub-Q once weekly may switch to 7 or 14 mg orally once daily.24 May begin oral dosing up to 7 days after last sub-Q dose.24 No equivalent oral dose for 1-mg sub-Q dose.24

Special Populations

No special population dosage recommendations.1 24

Cautions for Semaglutide

Contraindications

  • Personal or family history of MTC.1 2 24 25

  • MEN 2.1 2 24 25

  • Known hypersensitivity to semaglutide or any component in the formulation.1 2 24 25

Warnings/Precautions

Warnings

Risk of Thyroid C-Cell Tumors

Manufacturer of oral semaglutide (Rybelsus) recommends against use as first-line treatment for type 2 diabetes mellitus because of uncertain relevance of thyroid C-cell tumors found at clinically relevant exposures in rats and mice given GLP-1 receptor agonists.1 24 25 (See Boxed Warning.) Cases of MTC reported in patients receiving liraglutide, another GLP-1 receptor agonist, during postmarketing experience; data insufficient to establish or exclude a causal relationship between MTC and liraglutide use in humans.1 24 Unknown whether semaglutide causes thyroid C-cell tumors, including MTC, in humans.1 24

Very elevated serum calcitonin values may suggest MTC; such values generally exceed 50 ng/L in patients with MTC.1 24 Uncertain value of routine monitoring of serum calcitonin or thyroid ultrasound examinations; further evaluate patients if serum calcitonin is elevated or thyroid nodules noted on physical examination or neck imaging.1 24

Sensitivity Reactions

Hypersensitivity Reactions

Serious hypersensitivity reactions (anaphylaxis, angioedema) reported.1 24 If hypersensitivity reaction occurs, discontinue semaglutide and treat patient according to the standard of care and monitor patient until manifestations resolve.1 24 Use with caution in patients with a history of angioedema or anaphylaxis with another GLP-1 receptor agonist.1 24

Other Warnings and Precautions

Pancreatitis

Acute pancreatitis reported during clinical trials.1 24 FDA has been evaluating unpublished findings suggesting an increased risk of pancreatitis and precancerous cellular changes in patients with type 2 diabetes mellitus receiving incretin mimetics.21 22 Recent assessment of pancreatitis and pancreatic cancer risk in clinical trials,9 including meta-analyses of GLP-1 receptor agonist trials,42 43 have not confirmed these safety concerns with incretin mimetics.80

FDA has recommended that clinicians continue to follow the recommendations in the prescribing information for incretin mimetics.21 Observe patients carefully for manifestations of pancreatitis after drug initiation and dosage increases.1 24 Contact clinician promptly if symptoms of pancreatitis occur, including persistent severe abdominal pain that sometimes radiates to the back and that may or may not be accompanied by vomiting.1 24 Manufacturer states that if pancreatitis is suspected, promptly discontinue semaglutide and initiate appropriate management.1 24 If pancreatitis is confirmed, do not restart semaglutide.1 24

Safety and efficacy of semaglutide not established in patients with a history of pancreatitis; consider other antidiabetic agents in such patients.1 24

Diabetic Retinopathy Complications

In clinical trials, more events of diabetic retinopathy complications occurred in patients receiving oral or sub-Q semaglutide compared with those receiving placebo.1 9 24 Rapid improvement in glycemic control has been associated with a temporary worsening of diabetic retinopathy.1 24 Data are lacking on the effect of long-term glycemic control with semaglutide on diabetic retinopathy.1 24 Monitor patients with a history of diabetic retinopathy for progression of this condition.1 24

Sharing of Injection Pens

Do not share semaglutide (Ozempic) injection pens among patients, even if the needle has been changed; sharing poses risk for transmission of blood-borne pathogens.1

Use with Drugs Known to Cause Hypoglycemia

Patients receiving semaglutide in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin may have an increased risk of hypoglycemia; reduction in sulfonylurea or insulin dosage may be necessary.1 24

Renal Effects

Acute renal failure and worsening of chronic renal failure (sometimes requiring hemodialysis) reported with GLP-1 receptor agonists during postmarketing experience.1 24 Some patients did not have known underlying renal disease.1 24 Other factors (nausea, vomiting, diarrhea, or dehydration) were present in most patients.1 24 Because such adverse GI effects may worsen renal function, use caution when initiating semaglutide or escalating dosage in patients with renal impairment.1 24

In a pharmacokinetic study in patients with varying degrees of renal impairment, including end-stage renal disease (ESRD), adverse effects of oral semaglutide were consistent with those reported with other GLP-1 receptor agonists.38

Immunogenicity

Potential risk of immunogenicity.1 24 The presence of these antibodies has the potential to increase the risk of local skin reactions, hypersensitivity, or anaphylactic reactions and may also neutralize the therapeutic effects of GLP-1 receptor agonists; however, their clinical importance appears to be low in most patients.15 The in vitro neutralizing activity of the antibodies is unknown.1 24

Specific Populations

Pregnancy

Data are lacking on the use of semaglutide in pregnant women.1 24 Reproduction studies in animals using semaglutide have shown teratogenic effects.1 24 Embryofetal mortality, structural abnormalities, and alterations to growth observed in the offspring of rats who were administered semaglutide during organogenesis at dosages resulting in systemic exposures lower than the maximum recommended human dosage.1 24 In reproduction studies in rabbits and monkeys, early pregnancy loss and structural abnormalities were observed at dosages below the maximum recommended human dosage and at dosages ≥5 times the maximum recommended human dosage.1 24

Salcaprozate sodium (SNAC). an absorption enhancer in semaglutide oral tablets, crosses the placenta and reaches fetal tissues in rats.24 An increase in the length of gestation and number of stillbirths and a decrease in pup viability have been observed in animals given SNAC.24

Poorly controlled diabetes mellitus during pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortion, preterm delivery, and delivery complications and also increases risk of major fetal birth defects, stillbirth, and macrosomia-related morbidity.24

Use semaglutide during pregnancy only if the potential benefit justifies the potential risk to the fetus.1 24

Lactation

Semaglutide is distributed into milk in rats; not known whether distributed into milk in humans.1 24

Consider the benefits of breast-feeding and the importance of semaglutide to the woman along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1 24

Manufacturer states that breast-feeding is not recommended during treatment with oral semaglutide.24 25 SNAC has been detected in milk of lactating rats at levels 2–12 times higher than in maternal plasma following a single maternal administration.24

Pediatric Use

Safety and efficacy of semaglutide not established in children or adolescents younger than 18 years of age.1 24

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out. 1 24

Hepatic Impairment

No substantial differences in the pharmacokinetics of semaglutide administered orally or sub-Q have been observed in patients with mild, moderate, or severe hepatic impairment.1 24 39

Exposure of SNAC increased with increasing hepatic impairment; not considered clinically relevant.38 Data lacking on the long-term safety of SNAC in patients with hepatic impairment.38

Renal Impairment

No substantial differences in the pharmacokinetics of semaglutide administered orally or sub-Q have been observed in patients with mild, moderate, or severe renal impairment, including patients with ESRD.1 12 24 38

Exposure of SNAC increased with increasing renal impairment; not considered clinically relevant.38 Data lacking on the long-term safety of SNAC in patients with renal impairment.38 No effects of hemodialysis on pharmacokinetics of orally administered semaglutide or SNAC.38

Disease of the Upper GI Tract

No clinically important pharmacokinetic differences between patients with type 2 diabetes mellitus with or without upper GI disease (chronic gastritis and/or gastroesophageal reflux disease) who received oral semaglutide once daily for 10 consecutive days.24

Common Adverse Effects

Oral administration: Nausea,24 26 27 28 30 31 32 33 34 35 38 40 abdominal pain/discomfort,24 27 33 34 38 39 diarrhea,24 26 27 28 31 33 34 39 decreased appetite,24 26 27 28 33 34 39 40 vomiting,24 26 27 28 31 33 38 39 constipation.24 33 34 35

Sub-Q administration: Nausea,1 4 8 10 14 17 vomiting,1 4 8 14 17 diarrhea,1 4 8 14 abdominal pain,1 constipation.1 4

Drug Interactions

Low potential to inhibit or induce CYP enzymes or to inhibit drug transporters.1 24

Orally Administered Drugs

Possible decreased rate and extent of absorption of concomitantly administered oral drugs; use caution with concomitantly administered oral drugs.1 24 In clinical pharmacology trials, sub-Q semaglutide did not affect the absorption of orally administered drugs (e.g., atorvastatin, digoxin, metformin, ethinyl estradiol, levonorgestrel, warfarin) to any clinically important extent.1 13 16 24

No clinically important effects of oral semaglutide on absorption of other drugs (e.g., digoxin, ethinyl estradiol, levonorgestrel, furosemide, levothyroxine, lisinopril, metformin, omeprazole, rosuvastatin, warfarin) in drug interaction studies.24 40 41 Advise patients receiving oral semaglutide concomitantly with other oral drugs to closely follow oral semaglutide administration instructions.24 (See Oral Administration under Dosage and Administration.) Consider increased clinical or laboratory monitoring in patients receiving concomitant therapy with drugs that have a narrow therapeutic index or that require clinical monitoring.24

Specific Drugs

Drug

Interaction

Comments

Atorvastatin

No substantial change in atorvastatin peak plasma concentration or overall AUC1 13 24

No dosage adjustment necessary1 13 24

Digoxin

No substantial change in digoxin peak plasma concentration or overall AUC1 13 24

No dosage adjustment necessary1 13 24

Hormonal contraceptives, oral

No substantial change in ethinyl estradiol or levonorgestrel peak plasma concentrations or overall AUC1 16 24

No dosage adjustment necessary1 24

Insulin

Increased risk of hypoglycemia1 24

Consider reduced concomitant insulin dosage1 24

Levothyroxine

Levothyroxine total exposure (AUC) increased but peak plasma concentration unchanged with concomitant oral semaglutide24

Lisinopril

Lisinopril (20-mg single dose) in healthy individuals receiving oral semaglutide (20 mg once daily, at steady state) did not affect lisinopril exposure41

No lisinopril dosage adjustment necessary1 13 41

Metformin

No substantial change in metformin peak plasma concentration or overall AUC1 13 24

No metformin dosage adjustment necessary1 13 24

Omeprazole

No clinically important difference in pharmacokinetics of semaglutide (5 mg once daily for 5 days, then 10 mg once daily for 5 days) with concomitant omeprazole (40 mg once daily)24 40

No semaglutide dosage adjustment likely necessary40

Sulfonylureas

Increased risk of hypoglycemia1 24

Consider reduced concomitant sulfonylurea dosage1 24

Warfarin

No substantial change in peak plasma concentration or overall AUC of S- or R-warfarin1 13 24 41

No dosage adjustment necessary1 13 24 41

Semaglutide Pharmacokinetics

Absorption

Bioavailability

Sub-Q administration: 89–94% (absolute); exposure similar with administration in abdomen, thigh, or upper arm.1 10

Oral administration (coformulated with SNAC to facilitate absorption): 0.4–1% (absolute).24

Peak plasma concentration achieved in 1 hour (oral administration) or 1–3 days (sub-Q administration).1 10 24 Steady state achieved after 4–5 weeks with oral or sub-Q dosing.1 10 24

Distribution

Plasma Protein Binding

>99%.1 24

Elimination

Metabolism

Mainly proteolytic cleavage of the peptide backbone and sequential beta-oxidation of the fatty acid sidechain.1 24

Elimination Route

Mainly excreted in urine and feces.1 24 Approximately 3% of a dose is excreted in urine as unchanged drug.1 24

Half-life

Elimination half-life is approximately 1 week.1 24

Stability

Storage

Oral

20–25°C in original container; may expose to 15–30°C.24 Protect from moisture.24

Parenteral

Injection

Before first use, 2–8°C; do not freeze.1 After first use, can be stored at 15–30ºC or 2–8°C.1 Do not freeze and do not use if frozen; protect from excessive heat and light.1 3 When refrigerated, do not place injection pens directly next to the cooling element.3 Discard injection pen 56 days after first use.1 3

Actions

  • Long-acting GLP-1 receptor agonist; 94% amino acid sequence homology to endogenous human GLP-1.1 11 15 24

  • Stimulates insulin release in the presence of elevated glucose concentrations, suppresses glucose-dependent glucagon release, and slows gastric emptying, resulting in lower fasting and postprandial blood glucose concentrations and weight loss in patients with type 2 diabetes mellitus.1 15 17 24

  • Long-acting GLP-1 receptor agonists (e.g., albiglutide [no longer commercially available in the US], dulaglutide, exenatide extended-release, liraglutide, semaglutide) induce marked reductions in fasting plasma glucose (by stimulating insulin secretion) and modest reductions in postprandial glucose, while short-acting GLP-1 receptor agonists (e.g., exenatide, lixisenatide), have less of an effect on fasting plasma glucose concentrations and more of an effect on reducing postprandial glucose concentrations (by slowing gastric emptying and inhibiting glucagon secretion).15 17 24

  • Does not appear to be associated with clinically important prolongation of the corrected QT interval (QTc).1 24

Advice to Patients

Importance of patients reading the medication guide and instructions for use prior to initiating therapy and each time prescription is refilled.1 2 3 24 25

Importance of informing patients that semaglutide causes thyroid C-cell tumors in rats and that the relevance of this finding in humans is unknown.1 2 24 25 Importance of advising patients receiving semaglutide to report symptoms such as a lump in the neck, hoarseness, dysphagia, or dyspnea, which may be suggestive of thyroid cancer.1 2 24 25

Importance of informing patients of the possibility of pancreatitis with semaglutide therapy.1 2 24 25 Importance of informing patients about signs and symptoms of pancreatitis, including persistent severe abdominal pain sometimes radiating to the back that may or may not be accompanied by vomiting; importance of patient discontinuing semaglutide and promptly notifying clinician if such signs or symptoms occur.1 2 24 25

Importance of informing patients to contact a clinician if changes in vision are experienced during treatment with semaglutide.1 2 24 25

Importance of informing patients that they should never share injection pens containing semaglutide with another person, even if the needle is changed; sharing of the pen may pose a risk of transmitting or acquiring infection.1 2 24 25

Importance of informing patients of the potential risk of dehydration due to adverse GI effects; importance of advising patients to drink fluids to avoid dehydration.1 2 24 25 Importance of informing patients of the potential risk for worsening renal function, which in some cases may require dialysis.1 24 25

Importance of informing patients of possibility of hypersensitivity reactions (e.g., anaphylaxis).1 Patients should be instructed to discontinue semaglutide and promptly seek medical advice if symptoms of hypersensitivity occur.1 2 24 25

Importance of providing information regarding the potential risks and advantages of semaglutide therapy and of alternative modes of treatment.1

Importance of providing instruction regarding diabetes self-management practices, such as regular physical activity, adhering to meal planning, periodic blood glucose monitoring, HbA1c testing, recognition and management of hypoglycemia and hyperglycemia, and assessment of other diabetic complications.1 2 24 25 Advise patients to seek medical advice promptly during periods of stress (e.g., fever, trauma, infection, surgery) as medication requirements may change.1 2 24 25

Importance of advising patients that the most common adverse effects of oral semaglutide are nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation24 25 and that the most common adverse effects of sub-Q semaglutide therapy are nausea, vomiting, diarrhea, abdominal pain, and constipation.1 2 Advise patients that nausea, vomiting, and diarrhea are most common when first initiating oral or sub-Q semaglutide therapy but these effects decrease over time in most patients.1 24 25

Importance of informing patients if a dose of sub-Q semaglutide is missed, it should be administered as soon as possible within 5 days after the missed dose.1 2 If >5 days have passed, the missed dose should be skipped and the next dose should be administered on the regularly scheduled day.1 2 In each case, inform patients to resume their regular once-weekly dosing schedule.1 2 If a dose of oral semaglutide is missed, the dose should be skipped and the patient's regular once-daily schedule should be resumed the following day.24 25

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 24 25 Breastfeeding not recommended during treatment with oral semaglutide due to the unknown potential for serious adverse effects from accumulation of salcaprozate sodium (SNAC), an absorption enhancer in the oral formulation, in milk; alternative formulations of semaglutide (i.e., injection) are available for use during lactation.24 25

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 2 24 25

Importance of informing patients of other important precautionary information.1 2 24 25 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Semaglutide

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

3 mg

Rybelsus

Novo Nordisk

7 mg

Rybelsus

Novo Nordisk

14 mg

Rybelsus

Novo Nordisk

Parenteral

Injection, for subcutaneous use only

1.34 mg/mL

Ozempic (available as prefilled injection pen that delivers 0.25 or 0.5 mg)

Novo Nordisk

1.34 mg/mL

Ozempic (available as prefilled injection pen that delivers 1 mg)

Novo Nordisk

AHFS Drug Information. © Copyright 2021, Selected Revisions October 12, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Novo Nordisk. Ozempic (semaglutide) injection, for subcutaneous use prescribing information. Plainsboro, NJ; 2020 Jan.

2. Novo Nordisk. Ozempic (semaglutide) injection, for subcutaneous use medication guide. Plainsboro, NJ; 2020 Jan.

3. Novo Nordisk. Ozempic (semaglutide) injection, for subcutaneous use instructions for use. Plainsboro, NJ; 2020 Jan.

4. Sorli C, Harashima SI, Tsoukas GM et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. Lancet Diabetes Endocrinol. 2017; 5:251-260. http://www.ncbi.nlm.nih.gov/pubmed/28110911?dopt=AbstractPlus

5. Ahrén B, Masmiquel L, Kumar H et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol. 2017; 5:341-354. http://www.ncbi.nlm.nih.gov/pubmed/28385659?dopt=AbstractPlus

6. Ahmann AJ, Capehorn M, Charpentier G et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): a 56-week, open-label, randomized clinical trial. Diabetes Care. 2018; 41:258-266. http://www.ncbi.nlm.nih.gov/pubmed/29246950?dopt=AbstractPlus

7. Aroda VR, Bain SC, Cariou B et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017; 5:355-366. http://www.ncbi.nlm.nih.gov/pubmed/28344112?dopt=AbstractPlus

8. Rodbard HW, Lingvay I, Reed J et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): a randomized, controlled trial. J Clin Endocrinol Metab. 2018; 103:2291-2301. http://www.ncbi.nlm.nih.gov/pubmed/29688502?dopt=AbstractPlus

9. Marso SP, Bain SC, Consoli A et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016; 375:1834-1844. http://www.ncbi.nlm.nih.gov/pubmed/27633186?dopt=AbstractPlus

10. Hall S, Isaacs D, Clements JN. Pharmacokinetics and clinical implications of semaglutide: a new glucagon-like peptide (GLP)-1 receptor agonist. Clin Pharmacokinet. 2018; http://www.ncbi.nlm.nih.gov/pubmed/29915923?dopt=AbstractPlus

11. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 209637Orig1s000: Summary review. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209637Orig1s000SumR.pdf

12. Marbury TC, Flint A, Jacobsen JB et al. Pharmacokinetics and tolerability of a single dose of semaglutide, a human glucagon-like peptide-1 analog, in subjects with and without renal impairment. Clin Pharmacokinet. 2017; 56:1381-1390. http://www.ncbi.nlm.nih.gov/pubmed/28349386?dopt=AbstractPlus

13. Hausner H, Derving Karsbøl J, Holst AG et al. Effect of semaglutide on the pharmacokinetics of metformin, warfarin, atorvastatin and digoxin in healthy subjects. Clin Pharmacokinet. 2017; 56:1391-1401. http://www.ncbi.nlm.nih.gov/pubmed/28349387?dopt=AbstractPlus

14. Tuchscherer RM, Thompson AM, Trujillo JM. Semaglutide: the newest once-weekly GLP-1 RA for type 2 diabetes. Ann Pharmacother. 2018; :1060028018784583. http://www.ncbi.nlm.nih.gov/pubmed/29932006?dopt=AbstractPlus

15. Gentilella R, Pechtner V, Corcos A et al. Glucagon-like peptide-1 receptor agonists in type 2 diabetes treatment: are they all the same?. Diabetes Metab Res Rev. 2018; :e3070. http://www.ncbi.nlm.nih.gov/pubmed/30156747?dopt=AbstractPlus

16. Kapitza C, Nosek L, Jensen L et al. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. J Clin Pharmacol. 2015; 55:497-504. http://www.ncbi.nlm.nih.gov/pubmed/25475122?dopt=AbstractPlus

17. Samson SL, Garber AJ. A plethora of GLP-1 agonists: decisions about what to use and when. Curr Diab Rep. 2016; 16:120. http://www.ncbi.nlm.nih.gov/pubmed/27766579?dopt=AbstractPlus

21. US Food and Drug Administration. FDA Drug Safety Communication: FDA investigating reports of possible increased risk of pancreatitis and pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes. Silver Spring, MD; 2013 Mar 14. From FDA website. http://www.fda.gov/Drugs/DrugSafety/ucm343187.htm

22. Singh S, Chang HY, Richards TM et al. Glucagonlike peptide 1-based therapies and risk of hospitalization for acute pancreatitis in type 2 diabetes mellitus: a population-based matched case-control study. JAMA Intern Med. 2013; 173:534-9. http://www.ncbi.nlm.nih.gov/pubmed/23440284?dopt=AbstractPlus

23. Pratley RE, Aroda VR, Lingvay I et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018; 6:275-286. http://www.ncbi.nlm.nih.gov/pubmed/29397376?dopt=AbstractPlus

24. Novo Nordisk. Rybelsus (semaglutide) tablets, for oral use prescribing information. Plainsboro, NJ; 2020 Jan.

25. Novo Nordisk. Rybelsus (semaglutide) tablets, for oral use medication guide. Plainsboro, NJ; 2020 Jan.

26. Aroda VR, Rosenstock J, Terauchi Y et al. PIONEER 1: Randomized clinical trial of the efficacy and safety of oral semaglutide monotherapy in comparison with placebo in patients with type 2 diabetes. Diabetes Care 2019 Sep; 42(9): 1724-32.

27. Rodbard HW, Rosenstock J, Canani LH et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: The PIONEER 2 trial. Diabetes Care. 2019; 42:2272–81.

28. Rosenstock J, Allison D, Birkenfeld AL for the PIONEER 3 Investigators. Effect of additional oral semaglutide vs sitagliptin on glycated hemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: The PIONEER 3 randomized clinical trial. JAMA. 2019; 321(15):1466-80.

29. Pratley R, Amod A, Hoff ST et al, for the PIONEER 4 investigators. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): A randomised, double-blind, phase 3a trial. Lancet. 2019 Jul 6; 394:39-50. http://www.ncbi.nlm.nih.gov/pubmed/31186120?dopt=AbstractPlus

30. Mosenzon O, Blicher TM, Rosenlund S et al. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5 ) : a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019 Jul; 7(7):515-27.

31. Husain M, Birkenfeld AL, Donsmark M et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2019; 381:841-51.

32. Pieber TR, Bode B, Mertens A et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019; 7(7):528-39.

33. Zinman B, Aroda VR, Buse JB et al. Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: The PIONEER 8 trial. Diabetes Care. 2019; 42:2262–71.

34. Yamada Y, Katagiri H, Hamamoto Y et al. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020; 8:377–91.

35. Yabe D, Nakamura J, Kaneto H et al. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): An open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020 May; 8(5):392-406.

36. Nuhoho S, Gupta J. Hansen BB et al. Orally administered semaglutide versus GLP-1 RAs in patients with type 2 diabetes previously receiving 1–2 oral antidiabetics: Systematic review and network meta-analysis. Diabetes Ther. 2019; 10:2183–99.

37. Husain M, Bain SC, Jeppesen OK et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020; 22:442–51.

38. Granhall C, Søndergaard FL, Thomsen M et al. Pharmacokinetics, safety and tolerability of oral semaglutide in subjects with renal impairment. Clin Pharmacokinet. 2018; 57:1571–80.

39. Bækdal TA, Thomsen M, Kupcová V et al. Pharmacokinetics, safety, and tolerability of oral semaglutide in subjects with hepatic impairment. J Clin Pharmacol. 2018; 58(10):1314–23.

40. Bækdal TA, Breitschaft A, Navarria A et al. A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide. Expert Opin Drug Metab Toxicol. 14; 8:869-77.

41. Bækdal TA, Borregaard J, Hansen CW et al. Effects of oral semaglutide on the pharmacokinetics of lisinopril, warfarin, digoxin, and metformin in healthy subjects. Clin Pharmacokinet. 2019; 58:1193-1203.

42. Wang H, Liu Y, Tian Q et al. Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: a meta- analysis of randomized controlled trials. Diabetes Obes Metab. 2018 Apr; 20:910-20. http://www.ncbi.nlm.nih.gov/pubmed/29193572?dopt=AbstractPlus

43. Egan JM, Chia CW. Incretin therapy and pancreatic pathologies: background pathology versus drug-induced pathology in rats. Diabetes. 2014;63:1174–8.

80. Bonaventura A, Carbone S, Dixon DL et al. Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT-2 inhibitors and GLP-1 receptor agonists. J Intern Med. 2019; 286:16-31. http://www.ncbi.nlm.nih.gov/pubmed/30888088?dopt=AbstractPlus

81. Del Olmo-Garcia MI, Merino-Torres JF. GLP-1 receptor agonists and cardiovascular disease in patients with type 2 diabetes. J Diabetes Res. 2018; 2018:4020492. http://www.ncbi.nlm.nih.gov/pubmed/29805980?dopt=AbstractPlus

698. Garber AJ, Handelsman Y, Grunberger G et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm 2020 executive summary. Endocr Pract. 2020; 26:107-139. http://www.ncbi.nlm.nih.gov/pubmed/32022600?dopt=AbstractPlus

699. Zelniker TA, Wiviott SD, Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139:2022-2031. http://www.ncbi.nlm.nih.gov/pubmed/30786725?dopt=AbstractPlus

704. American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43:S98-S110. http://www.ncbi.nlm.nih.gov/pubmed/31862752?dopt=AbstractPlus

705. American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43:S111-S134. http://www.ncbi.nlm.nih.gov/pubmed/31862753?dopt=AbstractPlus

706. American Diabetes Association. 11. Microvascular complications and foot care: Standards of Medical Care in Diabetes-2020. Diabetes Care. 2020; 43:S135-S151. http://www.ncbi.nlm.nih.gov/pubmed/31862754?dopt=AbstractPlus

Frequently Asked Questions