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Semaglutide: Drug information

Semaglutide: Drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Semaglutide: Patient drug information" and "Semaglutide: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Special Alerts
Glucagon-Like Peptide-1 Receptor Agonists Safety Update January 2024

The FDA has been evaluating reports of suicidal thoughts or actions in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs). A preliminary evaluation has not found evidence that the use of these medicines causes suicidal thoughts or actions, but the FDA is continuing to investigate this issue. Patients should not stop taking GLP-1 RAs without consulting their health care provider. Health care providers should monitor for and advise patients using GLP-1 RAs to report new or worsening depression, suicidal thoughts, or any unusual changes in mood or behavior.

Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/update-fdas-ongoing-evaluation-reports-suicidal-thoughts-or-actions-patients-taking-certain-type.

ALERT: US Boxed Warning
Risk of thyroid C-cell tumors:

In rodents, semaglutide causes dose-dependent and treatment-duration-dependent thyroid C-cell tumors at clinically relevant exposures. It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

Semaglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk for MTC with the use of semaglutide and inform them of symptoms of thyroid tumors (eg, a mass in the neck, dysphagia, dyspnea, persistent hoarseness). Routine monitoring of serum calcitonin or using thyroid ultrasound is of uncertain value for early detection of MTC in patients treated with semaglutide.

Brand Names: US
  • Ozempic (0.25 or 0.5 MG/DOSE);
  • Ozempic (1 MG/DOSE);
  • Ozempic (2 MG/DOSE);
  • Rybelsus;
  • Wegovy
Brand Names: Canada
  • Ozempic (0.25 or 0.5 MG/DOSE);
  • Ozempic (1 MG/DOSE);
  • Rybelsus;
  • Wegovy;
  • Wegovy FlexTouch
Pharmacologic Category
  • Antidiabetic Agent, Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist
Dosing: Adult

Dosage guidance:

Clinical considerations: May require a dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia (Ref).

Diabetes mellitus, type 2, treatment

Diabetes mellitus, type 2, treatment (Ozempic, Rybelsus):

Note: May be used as an adjunctive agent or alternative monotherapy for patients in whom initial therapy with lifestyle intervention and metformin failed or those who cannot take metformin. May be preferred in patients who have or are at risk for atherosclerotic cardiovascular disease or who have chronic kidney disease (Ozempic only), when weight loss is desired, and/or in patients with an HbA1c relatively far from goal (eg, HbA1c 9% to 10%) and type 1 diabetes is not likely (Ref). Consider slower dose titration in patients with diabetic retinopathy to avoid exacerbating the condition (Ref). Due to lack of additive glycemic benefit, avoid concomitant use with a dipeptidyl peptidase-4 inhibitor (Ref).

Oral: Note: There are 2 formulations of Rybelsus (R1 and R2) with different recommended doses. These formulations are not substitutable on a mg per mg basis. Do not use more than one formulation at a time, and do not give more than 1 tablet/day.

R1 formulation (3, 7, and 14 mg tablets): Initial: 3 mg once daily for 30 days, then increase to 7 mg once daily. May increase to 14 mg once daily after 30 days on the 7 mg dose if needed to achieve glycemic goals. Note: The lower initial dose (3 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control.

R2 formulation (1.5, 4, and 9 mg tablets): Initial: 1.5 mg once daily for 30 days, then increase to 4 mg once daily. May increase to 9 mg once daily after 30 days on the 4 mg dose if needed to achieve glycemic goals. Note: The lower initial dose (1.5 mg daily) is intended to reduce GI symptoms; it does not provide effective glycemic control.

Conversion between R1 and R2 formulations: Do not switch between formulations during the first 30 days of therapy. When switching formulations, initiate the other formulation the day after discontinuing the previous formulation.

If taking 7 mg/day of the R1 formulation, switch to 4 mg/day of the R2 formulation (or vice versa).

If taking 14 mg/day of the R1 formulation, switch to 9 mg/day of the R2 formulation (or vice versa).

Missed dose: Missed dose should be skipped; resume at the next scheduled dose.

SUBQ: Initial: 0.25 mg once weekly for 4 weeks, then increase to 0.5 mg once weekly. May increase to 1 mg once weekly after 4 weeks on the 0.5 mg/week dose if needed to achieve glycemic goals; may increase further to 2 mg once weekly after 4 weeks on the 1 mg/week dose if needed to achieve glycemic goals (maximum: 2 mg/week). Note: The lower initial dose (0.25 mg weekly) is intended to reduce GI symptoms; it does not provide effective glycemic control. If changing the day of administration is necessary, allow at least 48 hours between 2 doses.

Missed dose: Missed dose should be administered as soon as possible within 5 days; resume usual schedule thereafter. If >5 days have elapsed, skip the missed dose and resume administration at the next scheduled weekly dose.

Conversion from Ozempic to oral semaglutide (R1 and R2 formulations):

If current SUBQ dose is 0.5 mg once weekly:

R1 formulation: Convert to 7 or 14 mg orally once daily, beginning 7 days after the last injection.

R2 formulation: Convert to 4 or 9 mg orally once daily, beginning 7 days after the last injection.

If current SUBQ dose is 0.25, 1, or 2 mg once weekly:

R1 and R2 formulations: There is no equivalent oral dose provided in the manufacturer's labeling.

Nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (off-label use): Note: For use in patients with histologic evidence or clinical diagnosis of nonalcoholic steatohepatitis and a BMI >27 kg/m2 or comorbid type 2 diabetes mellitus (Ref).

SUBQ: Initiate and adjust dose using the following schedule (Ref): If intolerance (eg, GI) occurs during dose escalation, remain at current dose for an additional week before increasing (Ref).

Week 1 through week 4: 0.25 mg once weekly.

Week 5 through week 8: 0.5 mg once weekly.

Week 9 through week 12: 1 mg once weekly.

Week 13 through week 16: 1.7 mg once weekly.

Week 17 and thereafter (target dosage): 2.4 mg once weekly.

Weight management, chronic

Weight management, chronic (Wegovy):

Note: For use as an adjunct to diet and exercise in patients with obesity, or in patients with overweight and ≥1 weight-related comorbidity (eg, dyslipidemia, hypertension, type 2 diabetes mellitus); may be preferred in patients with established cardiovascular disease (Ref). Some experts favor use in individuals with highest risk of weight-related complications based on evaluation of BMI and waist circumference (eg, BMI ≥30 kg/m2 or BMI 27 to <29.9 kg/m2 plus at least one weight-related comorbidity) (Ref).

SUBQ: Initiate and adjust dose using the following schedule: In patients who do not tolerate a dosage increase, consider delaying the increase for an additional 4 weeks:

Week 1 through week 4 : 0.25 mg once weekly.

Week 5 through week 8: 0.5 mg once weekly.

Week 9 through week 12: 1 mg once weekly.

Week 13 through week 16: 1.7 mg once weekly.

Week 17 and thereafter (maintenance dosage): 2.4 mg once weekly (preferred regimen); if not tolerated, may use an alternative maintenance dosage of 1.7 mg once weekly.

Note: The manufacturer recommends discontinuing therapy in patients who cannot tolerate the 1.7 mg/week dosage; however, some patients may achieve goal weight loss on a submaximal dose and may continue on the maximum tolerated dose (even if <1.7 mg/week) (Ref). Consider discontinuation if at least 5% of baseline body weight loss has not been achieved within 3 months (Ref).

Missed dose: Missed dose should be administered as soon as possible within 5 days; resume usual schedule thereafter. If >5 days have elapsed, skip the missed dose and resume administration at the next scheduled weekly dose. If 2 or more consecutive doses are missed, resume dosing as scheduled; alternatively, may reinitiate dosage adjustment schedule.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (Ref). Use caution when initiating or escalating doses; new-onset or worsening of existing renal failure has been reported, most commonly in patients experiencing volume depletion from GI losses (eg, vomiting, diarrhea, dehydration) (Ref).

Note: When SUBQ semaglutide (Ozempic) is used in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) to reduce risk of eGFR decline, end-stage kidney disease, and cardiovascular death, refer to adult dosing for patients without CKD. However, when feasible, titrate to a target maintenance dose of 1 mg once weekly. Further dose adjustments may be needed for glycemic control; refer to adult dosing for more information.

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzable (Ref): No supplemental dose or dosage adjustment necessary; use with caution due to limited clinical evidence (Ref).

Peritoneal dialysis: Unlikely to be dialyzable: No dosage adjustment necessary; use with caution due to limited clinical evidence (Ref).

Dosing: Liver Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Semaglutide: Pediatric drug information")

Weight management, chronic

Weight management, chronic

Note: Use as adjunct to diet and exercise. Escalate to maintenance dose slowly over at least 16 weeks to minimize GI side effects.

Children ≥12 years and Adolescents: Wegovy:

Initiation and titration: Initiate and adjust dose using the following schedule. In patients who do not tolerate a dosage increase, consider delaying the increase for an additional 4 weeks.

Weeks 1 through 4: SUBQ: 0.25 mg once weekly.

Weeks 5 through 8: SUBQ: 0.5 mg once weekly.

Weeks 9 through 12: SUBQ: 1 mg once weekly.

Weeks 13 through 16: SUBQ: 1.7 mg once weekly.

Maintenance:

Week 17 and beyond: SUBQ: 2.4 mg once weekly (preferred); if not tolerated, may decrease to 1.7 mg once weekly. Note: In the STEP TEENS trial, patients continued therapy on their maximum tolerated dose (Ref).

Dosing: Kidney Impairment: Pediatric

Altered kidney function:

Children ≥12 years and Adolescents: Wegovy: SUBQ:

Mild to severe impairment: No dosage adjustment necessary. Use caution when initiating or escalating doses; new-onset acute kidney injury or worsening of existing kidney failure has been reported, most commonly in patients experiencing volume depletion from GI losses (eg, vomiting, diarrhea, dehydration).

Dosing: Liver Impairment: Pediatric

Children ≥12 years and Adolescents: Wegovy: SUBQ: No dosage adjustment necessary.

Adverse Reactions (Significant): Considerations
Acute kidney injury

Acute kidney injury (AKI), which sometimes requires dialysis, has been reported with semaglutide and other glucagon-like peptide-1 receptor agonists. According to the manufacturer, AKI secondary to semaglutide was seen mostly in patients who had experienced nausea, vomiting, diarrhea, or dehydration. In a post-hoc analysis of multiple clinical trials, there was no difference in the incidence of acute kidney failure between semaglutide and comparators, including placebo (Ref).

Mechanism: Non–dose-related; exact mechanism is unknown. Pre-renal AKI may occur due to dehydration and volume contraction secondary to GI symptoms (eg, nausea, vomiting, diarrhea) (Ref).

Onset: Varied; because the mechanism is thought to be related to volume contraction, timing may be dependent on GI symptoms, initiation or dosage adjustment of concomitant medications, and/or comorbid conditions (Ref).

Risk factors:

• Volume contraction (eg, during periods of severe vomiting or diarrhea) (Ref)

• Co-administration of medications known to result in kidney injury during episodes of dehydration (eg, drugs that inhibit the renin-angiotensin system) (Ref)

• Preexisting kidney impairment

Diabetic retinopathy

An increased incidence of diabetic retinopathy complications (DRCs) was noted during the SUSTAIN-6 study, a clinical trial evaluating the impact of SUBQ semaglutide on cardiovascular outcomes in patients with type 2 diabetes; complications included vitreous hemorrhage, onset of diabetes-related blindness, and the need for treatment with an intravitreal agent or retinal photocoagulation (Ref). In a separate analysis of SUSTAIN clinical trial data, the effect was reported to be mainly observed in patients with preexisting diabetic retinopathy (DR) and primarily attributable to the magnitude and rapidity of reduction in HbA1c during the first 16 weeks of the trial (Ref). Clinicians should note that this effect has been observed with SUBQ semaglutide, exenatide, and dulaglutide but not other glucagon-like peptide-1 receptor agonists (Ref); trials are underway to better understand the long-term effects of semaglutide on diabetic eye disease (Ref). Oral semaglutide has not been associated with an increased incidence of DRC (Ref).

Mechanism: Unknown; in general, worsening of preexisting DR is a known consequence of rapid improvement of hyperglycemia, especially in patients with uncontrolled diabetes (Ref). Although unlikely, a direct toxic effect or potential angiogenic action of semaglutide has not been ruled out (Ref).

Onset: Varied; the increased incidence of DRC during the SUSTAIN-6 study may be attributed to the reduction in HbA1c at week 16 (Ref); however, clinicians should note that DR is a progressive condition, and the onset of DRCs may vary.

Risk factors:

• Preexisting DR (Ref)

• Large (>1.5%) and rapid (≤16 weeks) decline in HbA1c (Ref)

Gallbladder disease

Gallbladder disease and biliary tract disease, including cholelithiasis and cholecystitis, have been reported with glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide (Ref); some have required hospitalization or cholecystectomy (Ref). Resolution of biliary stones following discontinuation has been documented with other GLP-1 receptor agonists (eg, liraglutide) (Ref).

Mechanism: Dose- and time-related (Ref); not fully understood. Animal studies and in vitro data have demonstrated that GLP-1 enhances the proliferation and functional activity of cholangiocytes, which may result in gallbladder diseases (Ref). Some authors have postulated a change in bile acid production and secretion, suppressed secretion of cholecystokinin, decreased gallbladder emptying, prolonged gallbladder refilling, weight loss, or potentially a combination of these factors (Ref).

Onset: Varied (Ref); an increased risk was seen following >26 weeks of therapy (Ref).

Risk factors:

• Higher doses (eg, ≥1 mg SUBQ) (Ref)

• Longer duration of treatment (eg, >26 weeks) (Ref)

• Substantial or rapid weight loss

Gastrointestinal symptoms

GI effects, mainly abdominal pain, constipation, diarrhea, nausea, and vomiting, are the most common adverse reactions associated with glucagon-like peptide-1 receptor agonists, including semaglutide (Ref). Decreased appetite, dysgeusia, dyspepsia, and xerostomia have also been reported (Ref). GI effects tend to occur during dose escalation and decrease over time (Ref); may result in treatment discontinuation.

Rates of GI effects were shown to be similar between oral and once-weekly semaglutide 1 mg (Ref); high-dose once-weekly semaglutide (2.4 mg/week) may result in higher incidences of GI effects. In the SUSTAIN-7 trial comparing once-weekly semaglutide to once-weekly dulaglutide, rates of GI effects were similar for both doses of semaglutide (0.5 mg and 1 mg) and high-dose dulaglutide (1.5 mg) (Ref). The SUSTAIN-3 trial, which evaluated once-weekly semaglutide 1 mg and once-weekly exenatide 2 mg, showed a higher rate of GI effects with semaglutide treatment (Ref).

Mechanism: Dose-related; however, the exact mechanism is not fully understood. May be a result of delayed gastric emptying or activation of centers involved in appetite regulation, satiety, and nausea (Ref).

Onset: Intermediate; nausea, vomiting, and diarrhea are most common soon after initiation (eg, the first 4 weeks of treatment) and during dose escalation (Ref).

Risk factors:

• Dose; generally greater with higher doses

• Rapid titration

Hypersensitivity reactions

Serious, immediate hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with glucagon-like peptide-1 (GLP-1) receptor agonists (Ref). Exendin-based GLP-1 receptor agonists (eg, exenatide, lixisenatide) are associated with a doubling of reporting odds of anaphylactic reaction, compared with human-analogue GLP-1 receptor agonists (eg, liraglutide, dulaglutide, semaglutide) (Ref).

Mechanism: Non–dose-related; immunologic

Immediate hypersensitivity reactions: IgE-antibodies are formed against a drug allergen following initial exposure (Ref).

Onset: Immediate hypersensitivity reactions: Rapid; generally occurs within 1 hour of administration but may occur up to 6 hours after exposure (Ref).

Risk factors:

• Cross-reactivity between GLP-1 receptor agonists is unknown (Ref). Until further studies are available, semaglutide should be used with caution in patients with a history of anaphylaxis or angioedema to other GLP-1 receptor agonists. Skin tests have been used in patients with histories of immediate hypersensitivity reactions (Ref) and delayed hypersensitivity reactions (Ref).

Medullary thyroid carcinoma

In the early stages of drug development, thyroid C-cell tumors were noted to have developed during animal studies with semaglutide. It is unknown whether semaglutide causes thyroid C-cell tumors in humans, as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined. According to the manufacturer, human cases of medullary thyroid carcinoma (MTC) have been reported with liraglutide, another glucagon-like peptide-1 (GLP-1) receptor agonist.

Mechanism: Unknown; animal studies have shown dose-dependent and treatment duration-dependent harmful effects in rodents but not primates, thereby indicating that proliferative C-cell effects of liraglutide may be rodent specific. Humans have far fewer C cells than rodents, and expression of the GLP-1 receptor in human C cells is very low (Ref).

Risk factors:

• Patients with a personal or family history of MTC or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2) may be at an increased risk

Pancreatitis

Cases of acute pancreatitis (including hemorrhagic pancreatitis and necrotizing pancreatitis with some fatalities), chronic pancreatitis, and pancreatic adenocarcinoma have been reported with use of incretin-based therapies (eg, dipeptidyl peptidase 4 [DPP-4] inhibitors, glucagon-like peptide-1 [GLP-1] receptor agonists) (Ref). Acute pancreatitis was observed with semaglutide at rates similar to placebo during the SUSTAIN-6 trial (Ref).

Mechanism: Causality has not been firmly established (Ref). GLP-1 receptor agonists directly stimulate GLP-1 receptors in pancreatic islet beta cells and exocrine duct cells, which may cause an overgrowth of the cells that cover the smaller ducts, thereby resulting in hyperplasia, increased pancreatic weight, duct occlusion, back pressure, and subsequent acute or chronic pancreatic inflammation (Ref).

Onset: Not well characterized.

Risk factors:

• Patients with a prior history of pancreatitis may be at an increased risk for acute pancreatitis

• Patients with acute pancreatitis due to any cause are at an increased risk for progression to recurrent acute pancreatitis and then to chronic pancreatitis; patients with chronic pancreatitis are at an increased risk for pancreatic cancer (Ref)

• Risk factors for pancreatitis due to any cause include, but are not limited to, hypertriglyceridemia, cholelithiasis, alcohol use, and obesity

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults, unless otherwise noted.

>10%:

Gastrointestinal: Abdominal pain (adolescents, adults: 6% to 20%) (table 1), constipation (oral: 5% to 6%; SUBQ: adolescents: 6%; adults: 3% to 24%) (table 2), diarrhea (oral: 9% to 10%; SUBQ: adolescents, adults: 9% to 30%) (table 3), nausea (oral: 11% to 20%; SUBQ: adolescents, adults: 16% to 44%) (table 4), vomiting (oral: 6% to 8%; SUBQ: adolescents: 36%, adults: 5% to 24%) (table 5)

Semaglutide: Adverse Reaction: Abdominal Pain

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

15%

6%

Adolescents

2.4 mg/week

SUBQ

133

67

20%

10%

Adults

2.4 mg/week

SUBQ

2,116

1,261

11%

4%

Adults

14 mg/day

Oral

356

362

10%

4%

Adults

7 mg/day

Oral

356

362

7%

5%

Adults

0.5 mg/week

SUBQ

260

262

6%

5%

Adults

1 mg/week

SUBQ

261

262

Semaglutide: Adverse Reaction: Constipation

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

6%

2%

Adolescents

2.4 mg/week

SUBQ

133

67

24%

11%

Adults

2.4 mg/week

SUBQ

2,116

1,261

6%

2%

Adults

7 mg/day

Oral

356

362

5%

2%

Adults

14 mg/day

Oral

356

362

5%

2%

Adults

0.5 mg/week

SUBQ

260

262

3%

2%

Adults

1 mg/week

SUBQ

261

262

Semaglutide: Adverse Reaction: Diarrhea

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

22%

19%

Adolescents

2.4 mg/week

SUBQ

133

67

30%

16%

Adults

2.4 mg/week

SUBQ

2,116

1,261

10%

4%

Adults

14 mg/day

Oral

356

362

9%

4%

Adults

7 mg/day

Oral

356

362

9%

2%

Adults

0.5 mg/week

SUBQ

260

262

9%

2%

Adults

1 mg/week

SUBQ

261

262

Semaglutide: Adverse Reaction: Nausea

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

42%

18%

Adolescents

2.4 mg/week

SUBQ

133

67

44%

16%

Adults

2.4 mg/week

SUBQ

2,116

1,261

20%

6%

Adults

1 mg/week

SUBQ

261

262

20%

6%

Adults

14 mg/day

Oral

356

362

16%

6%

Adults

0.5 mg/week

SUBQ

260

262

11%

6%

Adults

7 mg/day

Oral

356

362

Semaglutide: Adverse Reaction: Vomiting

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

36%

10%

Adolescents

2.4 mg/week

SUBQ

133

67

24%

6%

Adults

2.4 mg/week

SUBQ

2,116

1,261

9%

2%

Adults

1 mg/week

SUBQ

261

262

8%

3%

Adults

14 mg/day

Oral

356

362

6%

3%

Adults

7 mg/day

Oral

356

362

5%

2%

Adults

0.5 mg/week

SUBQ

260

262

Nervous system: Fatigue (SUBQ: 11%), headache (SUBQ: adolescents, adults: 14% to 17%)

Respiratory: Nasopharyngitis (SUBQ: adolescents: 12%)

1% to 10%:

Cardiovascular: Hypotension (SUBQ: adolescents, adults: 1% to 2%; including orthostatic hypotension)

Dermatologic: Alopecia (SUBQ: adolescents, adults: 3% to 4%), skin rash (SUBQ: adolescents: 3%), urticaria (SUBQ: adolescents: 3%)

Endocrine & metabolic: Diabetic retinopathy (complications: 3% to 7%; vitreous hemorrhage: 1%; blindness: <1%) (Ref), hypoglycemia (SUBQ: 2% to 6%), severe hypoglycemia (≤1%)

Gastrointestinal: Abdominal distention (2% to 7%), cholelithiasis (adolescents, adults: 0% to 4%) (table 6), decreased appetite (oral: 6% to 9%) (table 7), dysgeusia (SUBQ: ≤2%), dyspepsia (oral: 0.6% to 3%; SUBQ: 3% to 9%) (table 8), eructation (adolescents, adults: ≤7%), flatulence (1% to 6%), gastritis (2% to 4%), gastroenteritis (SUBQ: adolescents, adults: 6% to 7%), gastroesophageal reflux disease (adolescents, adults: 2% to 5%), viral gastroenteritis (SUBQ: 4%)

Semaglutide: Adverse Reaction: Cholelithiasis

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

4%

0%

Adolescents

2.4 mg/week

SUBQ

133

67

2%

0.7%

Adults

2.4 mg/week

SUBQ

2,116

1,261

2%

0%

Adults

0.5 mg/week

SUBQ

260

262

1%

0%

Adults

7 mg/day

Oral

356

362

0.4%

0%

Adults

1 mg/week

SUBQ

261

262

0%

0%

Adults

14 mg/day

Oral

356

362

Semaglutide: Adverse Reaction: Decreased Appetite

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

9%

1%

Adults

14 mg/day

Oral

356

362

6%

1%

Adults

7 mg/day

Oral

356

362

Semaglutide: Adverse Reaction: Dyspepsia

Drug (Semaglutide)

Placebo

Population

Dose

Dosage Form

Number of Patients (Semaglutide)

Number of Patients (Placebo)

9%

3%

Adults

2.4 mg/week

SUBQ

2,116

1,261

4%

2%

Adults

0.5 mg/week

SUBQ

260

262

3%

2%

Adults

1 mg/week

SUBQ

261

262

3%

0.6%

Adults

7 mg/day

Oral

356

362

0.6%

0.6%

Adults

14 mg/day

Oral

356

362

Genitourinary: Urinary tract infection (SUBQ: adolescents: 4%), urolithiasis (SUBQ: 1%)

Hepatic: Increased serum alanine aminotransferase (SUBQ: adolescents: 3%)

Immunologic: Antibody development (≤3%)

Infection: Influenza (SUBQ: adolescents: 3%)

Nervous system: Anxiety (SUBQ: adolescents: 4%), dizziness (SUBQ: adolescents, adults: 8%), dysesthesia (SUBQ: 2%; including allodynia, burning sensation, hyperesthesia, paresthesia)

Neuromuscular & skeletal: Bone fracture (SUBQ: 1% to 2%), sprain (ligament: SUBQ: adolescents: 4%)

Respiratory: Sinusitis (SUBQ: adolescents: 4%)

<1%:

Gastrointestinal: Acute pancreatitis (including hemorrhagic pancreatitis, necrotizing pancreatitis), cholecystitis (SUBQ: adolescents, adults)

Local: Discomfort at injection site (SUBQ), erythema at injection site (SUBQ)

Frequency not defined: Gastrointestinal: Hemorrhoids (SUBQ), hiccups (SUBQ), increased serum amylase (adolescents, adults: mean increase from baseline of 10% to 16%), increased serum lipase (adolescents, adults: mean increase from baseline of 22% to 39%)

Postmarketing (any formulation or population):

Cardiovascular: Increased heart rate (Ref)

Dermatologic: Bullous pemphigoid (Ref)

Gastrointestinal: Biliary tract disease (Ref), cholecystectomy, delayed gastric emptying (Ref), gallbladder disease (Ref), intestinal obstruction, xerostomia (Ref)

Hepatic: Hepatic injury (increased serum alkaline phosphatase, jaundice, biliary cirrhosis) (Ref)

Hypersensitivity: Anaphylaxis (Ref), angioedema (Ref)

Nervous system: Dysesthesia

Neuromuscular & skeletal: Lupus erythematosus (Ref)

Renal: Acute interstitial nephritis (Ref), acute kidney injury (Ref)

Contraindications

Hypersensitivity to semaglutide or any component of the formulation; personal or family history of medullary thyroid carcinoma (MTC); patients with multiple endocrine neoplasia syndrome type 2 (MEN2)

Canadian labeling: Additional contraindications (not in US labeling): Pregnancy; breastfeeding

Warnings/Precautions

Concerns related to adverse effects:

• Psychiatric effects: Suicidal behavior has been reported with other medications used for weight management. Avoid use in patients with history of suicidal attempts or active suicidal ideation.

Disease-related concerns:

• Bariatric surgery:

- Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy, and closely monitor the patient for the duration of therapy; acute and chronic kidney failure exacerbation may occur. A majority of cases occurred in patients with nausea, vomiting, diarrhea, and/or dehydration. Nausea is common and fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).

- Excessive glucagon-like peptide-1 exposure: Closely monitor for efficacy and assess for signs and symptoms of pancreatitis if therapy is initiated after surgery; gastric bypass and sleeve gastrectomy (but not gastric band) significantly increase endogenous postprandial GLP-1 concentrations (Korner 2009; Peterli 2012). Administration of exogenous GLP-1 agonists may be redundant to surgery effects.

Concurrent drug therapy issues:

• Delayed gastric emptying: Semaglutide slows gastric emptying, which may alter the absorption of other medications. Monitor narrow therapeutic index medications for increased or decreased response.

Dosage form specific issues:

• Multiple dose injection pens (Ozempic): According to the CDC, pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of infection. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).

Other warnings/precautions:

• Appropriate use:

- Diabetes mellitus: Do not use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis; not a substitute for insulin.

- Weight loss: Safety and effectiveness in combination with other products intended for weight loss have not been established.

• Surgical and endoscopic procedures: Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has been associated with elevated residual gastric contents, which may increase the risk for adverse events during anesthesia and deep sedation (including aspiration) (Kobori 2023; Marroquin-Harris 2023; Silveira 2023). In some studies, delayed gastric emptying induced by GLP-1 RAs returned to baseline after 8 to 12 weeks of continuous therapy; therefore, risk may be higher in patients who recently initiated therapy or who use GLP-1 RAs intermittently (Raven 2024; van Zuylen 2024). Although the American Society of Anesthesiologists has suggested holding GLP-1 RAs prior to planned procedures requiring general anesthesia, the risks and benefits of this approach have not been evaluated (AGA [Hashash 2023]; ASA [Joshi 2023]). For example, in patients using GLP-1 RAs for glycemic control, holding the medication may result in perioperative hyperglycemia and increase the risk of adverse postoperative outcomes (AGA [Hashash 2023]; van Zuylen 2024). Individualize the decision to hold the GLP-1 RA based on patient-specific factors such as the indication (eg, glycemic control vs weight management), duration and frequency of therapy, presence of adverse GI symptoms, and concomitant medications that may slow gastric emptying (eg, opioids, proton pump inhibitors); may consider additional preoperative interventions (eg, clear liquid diet, full stomach precautions, gastric ultrasound) on a case-by-case basis to reduce risk (ASA [Hashash 2023]; Marroquin-Harris 2023; Raven 2024; van Zuylen 2024). Refer also to institutional protocols.

Product Availability

Rybelsus (formulation R2) 1.5 mg, 4 mg, 9 mg tablets: FDA approved December 2024; anticipated availability in December 2025. Rybelsus (formulation R2) 1.5 mg, 4 mg, 9 mg tablets are not interchangeable with Rybelsus (formulation R1) 3 mg, 7 mg, and 14 mg tablets.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Auto-injector, Subcutaneous:

Wegovy: 0.25 mg/0.5 mL (0.5 mL); 0.5 mg/0.5 mL (0.5 mL); 1 mg/0.5 mL (0.5 mL); 1.7 mg/0.75 mL (0.75 mL); 2.4 mg/0.75 mL (0.75 mL)

Solution Pen-injector, Subcutaneous:

Ozempic (0.25 or 0.5 MG/DOSE): 2 mg/3 mL (3 mL); 0.25 mg or 0.5 mg per dose [2 mg/1.5 mL] (1.5 mL [DSC]) [contains phenol, propylene glycol]

Ozempic (1 MG/DOSE): 1 mg per dose [4 mg/3 mL] (3 mL); 1 mg per dose [2 mg/1.5 mL] (1.5 mL [DSC]) [contains phenol, propylene glycol]

Ozempic (2 MG/DOSE): 8 mg/3 mL (3 mL) [contains phenol, propylene glycol]

Tablet, Oral:

Rybelsus: 3 mg, 7 mg, 14 mg

Generic Equivalent Available: US

No

Pricing: US

Solution Auto-injector (Wegovy Subcutaneous)

0.25 mg/0.5 mL (per 0.5 mL): $404.71

0.5 mg/0.5 mL (per 0.5 mL): $404.71

1 mg/0.5 mL (per 0.5 mL): $404.71

1.7 mg/0.75 mL (per 0.75 mL): $404.71

2.4 mg/0.75 mL (per 0.75 mL): $404.71

Solution Pen-injector (Ozempic (0.25 or 0.5 MG/DOSE) Subcutaneous)

2 mg/3 mL (per mL): $399.03

Solution Pen-injector (Ozempic (1 MG/DOSE) Subcutaneous)

4 mg/3 mL (per mL): $399.03

Solution Pen-injector (Ozempic (2 MG/DOSE) Subcutaneous)

8 mg/3 mL (per mL): $399.03

Tablets (Rybelsus Oral)

3 mg (per each): $39.90

7 mg (per each): $39.90

14 mg (per each): $39.90

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Auto-injector, Subcutaneous:

Wegovy: 0.25 mg/0.5 mL (0.5 mL); 0.5 mg/0.5 mL (0.5 mL); 1 mg/0.5 mL (0.5 mL); 1.7 mg/0.75 mL (0.75 mL); 2.4 mg/0.75 mL (0.75 mL)

Solution Pen-injector, Subcutaneous:

Ozempic (0.25 or 0.5 MG/DOSE): 2 mg/3 mL (3 mL); 0.25 mg or 0.5 mg per dose [2 mg/1.5 mL] (1.5 mL) [contains phenol, propylene glycol]

Ozempic (1 MG/DOSE): 1 mg per dose [4 mg/3 mL] (1.5 mL) [contains phenol, propylene glycol]

Wegovy FlexTouch: 0.25 mg/dose (1.5 mL); 0.5 mg/dose (1.5 mL); 1 mg/dose (3 mL); 1.7 mg/dose (3 mL); 2.4 mg/dose (3 mL) [contains phenol, propylene glycol]

Tablet, Oral:

Rybelsus: 3 mg, 7 mg, 14 mg

Administration: Adult

Oral: Administer in the morning on an empty stomach with up to 4 ounces of plain water only, ≥30 minutes before eating food, drinking beverages, or taking other oral medications. Swallow tablets whole; do not split, crush, or chew.

SUBQ: Administer by SUBQ injection into the abdomen, thigh, or upper arm at any time of day on the same day each week, with or without food. If changing the day of administration is necessary, allow ≥48 hours between 2 doses. Rotate injection sites weekly if injecting in the same area of the body. Do not mix with other products (administer as separate injections). Avoid adjacent injections if administering other agents in the same area of the body. Solution should be clear; do not use if particulate matter and coloration are seen.

Ozempic: For each new prefilled pen, prime the needle before the first injection by turning the dose selector to the flow check symbol and injecting into the air (priming is not required for subsequent injections). Use a new needle for each injection. Once injected, continue to depress the button until the dial has returned to 0 and for an additional 6 seconds. Then, remove the needle from the skin.

Wegovy: After removal of the pen cap, the needle will be hidden inside the needle cover. To begin injection, press the needle cover firmly against the skin. Once injected, continue to press the device against the skin until the yellow bar has stopped moving. Then, remove the needle from the skin.

Administration: Pediatric

SUBQ: Wegovy: Administer by SUBQ injection into the abdomen (do not inject within 2 inches of belly button), thigh, or upper arm at any time of day on the same day each week, with or without food. Solution should be clear; do not use if particulate matter and coloration are seen; do not mix with other products. After removal of the pen cap, the needle will be hidden inside the needle cover. To begin injection, press the needle cover firmly against the skin, continue to press the device against the skin until the yellow bar has stopped moving. Then, slowly remove the needle from the skin and dispose of pen. Rotate injection sites weekly if injecting in the same area of the body. Do not inject into areas that are tender, bruised, red, or hard, or have scars or stretch marks. If changing the day of administration is necessary, allow ≥2 days between 2 doses.

Missed doses: If one dose is missed and the next scheduled dose is >2 days away, administer the missed dose as soon as possible. If one dose is missed and the next scheduled dose is <2 days away, do not administer the missed dose and resume dosing on the regularly scheduled day of the week. If 2 or more doses are missed, may either resume at the next regularly scheduled day of the week or may consider reinitiating semaglutide and follow the dose escalation schedule.

Hazardous Drugs Handling Considerations

This medication is not on the National Institute for Occupational Safety and Health (NIOSH) (2024) list; however, it may meet the criteria for a hazardous drug. Semaglutide may cause carcinogenicity.

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).

Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Ozempic: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209637s025lbl.pdf#page=32

Rybelsus: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/213051s012lbl.pdf

Wegovy: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/215256s011lbl.pdf#page=35

Use: Labeled Indications

Diabetes mellitus, type 2, treatment (Ozempic, Rybelsus): As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus; risk reduction of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction [MI], nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (Ozempic only); risk reduction of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes mellitus and chronic kidney disease (Ozempic only).

Weight management, chronic (Wegovy): As an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults and pediatric patients ≥12 years of age with obesity, or in adults with overweight and at least one weight-related comorbid condition (eg, dyslipidemia, hypertension, type 2 diabetes mellitus); risk reduction of major adverse cardiovascular events (cardiovascular death, nonfatal MI, nonfatal stroke) in adults with established cardiovascular disease and either obesity or overweight.

Use: Off-Label: Adult

Nonalcoholic steatohepatitis

Medication Safety Issues
Other safety concerns:

Cross-contamination may occur if pens are shared among multiple patients. Steps should be taken to prohibit sharing of pens.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Alectinib: Glucagon-Like Peptide-1 Agonists may decrease serum concentration of Alectinib. Risk C: Monitor

Alpha-Lipoic Acid: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Androgens: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Beta-Blockers (Beta1 Selective): May increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor

Beta-Blockers (Nonselective): May increase hypoglycemic effects of Antidiabetic Agents. Beta-Blockers (Nonselective) may increase adverse/toxic effects of Antidiabetic Agents. Specifically, beta-blockers may mask the hypoglycemic symptoms of antidiabetic agents. Risk C: Monitor

Bortezomib: May increase therapeutic effects of Antidiabetic Agents. Bortezomib may decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Direct Acting Antiviral Agents (HCV): May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Etilefrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Furosemide: May decrease therapeutic effects of Semaglutide. Semaglutide may increase serum concentration of Furosemide. Risk C: Monitor

Glucagon-Like Peptide-1 Agonists: Semaglutide may increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid

Guanethidine: May increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor

Hyperglycemia-Associated Agents: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Hypoglycemia-Associated Agents: Antidiabetic Agents may increase hypoglycemic effects of Hypoglycemia-Associated Agents. Risk C: Monitor

Insulin: Glucagon-Like Peptide-1 Agonists may increase hypoglycemic effects of Insulin. Management: Consider insulin dose reductions when used in combination with glucagon-like peptide-1 agonists. Monitor patients for hypoglycemia. Risk D: Consider Therapy Modification

Levothyroxine: Semaglutide may increase serum concentration of Levothyroxine. Risk C: Monitor

Liraglutide: May increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid

Maitake: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Meglitinides: Glucagon-Like Peptide-1 Agonists may increase hypoglycemic effects of Meglitinides. Management: Consider meglitinide dose reductions when used in combination with glucagon-like peptide-1 agonists, particularly when also used with basal insulin. Risk D: Consider Therapy Modification

Monoamine Oxidase Inhibitors: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Pegvisomant: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Prothionamide: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Quinolones: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Quinolones may decrease therapeutic effects of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor

Reproterol: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Ritodrine: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Salicylates: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Selective Serotonin Reuptake Inhibitor: May increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Sincalide: Drugs that Affect Gallbladder Function may decrease therapeutic effects of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider Therapy Modification

Sulfonylureas: Glucagon-Like Peptide-1 Agonists may increase hypoglycemic effects of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with glucagon-like peptide-1 agonists. Risk D: Consider Therapy Modification

Thiazide and Thiazide-Like Diuretics: May decrease therapeutic effects of Antidiabetic Agents. Risk C: Monitor

Tirzepatide: May increase adverse/toxic effects of Glucagon-Like Peptide-1 Agonists. Risk X: Avoid

Reproductive Considerations

Glucagon-like peptide-1 (GLP-1) receptor agonists are not recommended for patients with type 2 diabetes mellitus planning to become pregnant. Patients who could become pregnant should use effective contraception during therapy. Transition to a preferred therapy should be initiated prior to conception and contraception should be continued until glycemic control is achieved (ADA 2024; Alexopoulos 2019; Egan 2020)

When used for the treatment of diabetes mellitus or weight loss management, semaglutide should be discontinued for ≥2 months prior to becoming pregnant.

GLP-1 receptor agonists, including semaglutide, have been evaluated to manage metabolic aspects of polycystic ovary syndrome (PCOS), including decreasing weight and improving fertility (Goldberg 2024a; Goldberg 2024b; Jensterle 2022). GLP-1 receptor agonists, in combination with lifestyle interventions, can be considered for weight management in adults with PCOS and excess weight or obesity. However, until additional data are available, use in patients with PCOS to improve reproductive outcomes should be limited to research settings (Teede 2024).

Pregnancy Considerations

Outcome data following exposure to glucagon-like peptide-1 receptor agonists, including semaglutide, during pregnancy are limited (Cesta 2024; Dao 2024; Okeke 2024; Skov 2023).

Poorly controlled diabetes during pregnancy is associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major malformations, stillbirth, and macrosomia (ACOG 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2024).

Agents other than semaglutide are currently recommended to treat diabetes mellitus during pregnancy (ADA 2024).

An increased risk of adverse maternal and fetal events is associated with obesity; however, moderate gestational weight gain based on prepregnancy BMI is required for positive fetal outcomes in all pregnancies, including patients with excess weight or obesity. Therefore, medications for weight loss therapy are not recommended during pregnancy (ACOG 2021; Wharton 2020).

Data collection to monitor pregnancy and infant outcomes following exposure to semaglutide is ongoing. Health care providers are encouraged to enroll patients exposed to semaglutide during pregnancy in the registry by contacting Novo Nordisk (1-877-390-2760 or https://www.wegovypregnancyregistry.com). Patients may also enroll themselves.

Breastfeeding Considerations

It is not known if semaglutide is present in breast milk. The oral formulation also contains salcaprozate sodium (SNAC); it is not known if SNAC is present in breast milk.

According to the manufacturer, the decision to breastfeed during therapy with injectable semaglutide should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfeeding during therapy with oral semaglutide is not recommended due to the unknown risks associated with potential accumulation of SNAC in the infant.

Dietary Considerations

Oral: Administer in the morning on an empty stomach with up to 4 ounces of plain water only, ≥30 minutes before eating food, drinking beverages, or taking other oral medications.

Monitoring Parameters

Plasma glucose (individualize frequency based on treatment regimen, hypoglycemia risk, and other patient-specific factors) (ADA 2023); heart rate and body weight (if used for chronic weight management); renal function (especially when initiating therapy or increasing doses in patients reporting severe adverse GI reactions); signs/symptoms of pancreatitis (eg, persistent severe abdominal pain which may radiate to the back and which may or may not be accompanied by vomiting); triglycerides; signs/symptoms of gallbladder disease; worsening of diabetic retinopathy (particularly in those with a prior history of the disease).

HbA1c: Monitor at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; monitor quarterly in patients in whom treatment goals have not been met, or with therapy change. Note: In patients prone to glycemic variability (eg, patients with insulin deficiency), or in patients whose HbA1c is discordant with serum glucose levels or symptoms, consider evaluating HbA1c in combination with blood glucose levels and/or a glucose management indicator (ADA 2023; KDIGO 2020).

Routine monitoring of serum calcitonin or using thyroid ultrasound monitoring is of uncertain value for early detection of medullary thyroid carcinoma in patients treated with semaglutide.

Reference Range

Recommendations for glycemic control in patients with diabetes:

Nonpregnant adults (AACE [Samson 2023]; ADA 2023):

HbA1c: <7% (a more aggressive [<6.5%] or less aggressive [<8%] HbA1c goal may be targeted based on patient-specific characteristics). Note : In patients using a continuous glucose monitoring system, a goal of time in range >70% with time below range <4% is recommended and is similar to a goal HbA1c <7%.

Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).

Peak postprandial capillary blood glucose (~1 to 2 hours after a meal): <180 mg/dL (SI: <10 mmol/L) (more or less stringent goals may be appropriate based on patient-specific characteristics).

Older adults (≥65 years of age) (ADA 2023):

Note: Consider less strict targets in patients who are using insulin and/or insulin secretagogues (eg, sulfonylureas, meglitinides) (ES [LeRoith 2019]).

HbA1c: <7% to 7.5% (healthy); <8% (complex/intermediate health). Note: Individualization may be appropriate based on patient and caregiver preferences and/or presence of cognitive impairment. In patients with very complex or poor health (ie, limited remaining life expectancy), consider making therapy decisions based on avoidance of hypoglycemia and symptomatic hyperglycemia rather than HbA1c level.

Preprandial capillary blood glucose: 80 to 130 mg/dL (SI: 4.4 to 7.2 mmol/L) (healthy); 90 to 150 mg/dL (SI: 5 to 8.3 mmol/L) (complex/intermediate health); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (very complex/poor health).

Bedtime capillary blood glucose: 80 to 180 mg/dL (SI: 4.4 to 10 mmol/L) (healthy); 100 to 180 mg/dL (SI: 5.6 to 10 mmol/L) (complex/intermediate health); 110 to 200 mg/dL (SI: 6.1 to 11.1 mmol/L) (very complex/poor health).

Classification of hypoglycemia (ADA 2023):

Level 1: 54 to 70 mg/dL (SI: 3 to 3.9 mmol/L); hypoglycemia alert value; initiate fast-acting carbohydrate (eg, glucose) treatment.

Level 2: <54 mg/dL (SI: <3 mmol/L); threshold for neuroglycopenic symptoms; requires immediate action.

Level 3: Hypoglycemia associated with a severe event characterized by altered mental and/or physical status requiring assistance.

Mechanism of Action

Semaglutide is a selective glucagon-like peptide-1 (GLP-1) receptor agonist that increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, slows gastric emptying; also acts in the areas of the brain involved in regulation of appetite and caloric intake.

Pharmacokinetics (Adult Data Unless Noted)

Distribution: Vd: Oral: ~8 L; SUBQ: ~12.5 L.

Protein binding: >99% to albumin.

Metabolism: Proteolytic cleavage of the peptide backbone with sequential beta-oxidation of the fatty acid sidechain.

Bioavailability: Oral: ~0.4% to 1% (R1 formulation), ~1% to 2% (R2 formulation); SUBQ: 89%.

Half-life elimination: ~1 week.

Time to peak, plasma: Oral: 1 hour; SUBQ: 1 to 3 days.

Excretion: Urine (~3% as unchanged drug), feces.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Ozempic | Rybelsus | Wegovy flextouch;
  • (AR) Argentina: Ozempic | Rybelsus;
  • (AT) Austria: Ozempic | Wegovy;
  • (AU) Australia: Ozempic;
  • (BD) Bangladesh: Fitaro | Orsema | Ozempic | Sematid;
  • (BE) Belgium: Ozempic | Rybelsus;
  • (BG) Bulgaria: Ozempic | Rybelsus;
  • (BR) Brazil: Ozempic | Rybelsus;
  • (CH) Switzerland: Ozempic | Rybelsus | Wegovy fixdose | Wegovy multi fixdose;
  • (CL) Chile: Rybelsus;
  • (CO) Colombia: Ozempic | Rybelsus;
  • (CZ) Czech Republic: Ozempic | Rybelsus;
  • (DE) Germany: Ozempic;
  • (DK) Denmark: Rybelsus | Wegovy;
  • (DO) Dominican Republic: Ozempic;
  • (EE) Estonia: Ozempic | Rybelsus;
  • (EG) Egypt: Ozempic;
  • (ES) Spain: Ozempic | Rybelsus;
  • (FI) Finland: Ozempic | Rybelsus | Wegovy flextouch;
  • (FR) France: Ozempic | Rybelsus | Wegovy | Wegovy flextouch;
  • (GB) United Kingdom: Ozempic | Rybelsus | Wegovy flextouch;
  • (GR) Greece: Ozempic;
  • (HK) Hong Kong: Ozempic;
  • (HR) Croatia: Ozempic | Rybelsus;
  • (HU) Hungary: Ozempic | Rybelsus;
  • (IE) Ireland: Ozempic | Rybelsus;
  • (IT) Italy: Ozempic | Rybelsus;
  • (JO) Jordan: Ozempic;
  • (JP) Japan: Ozempic | Rybelsus;
  • (KW) Kuwait: Ozempic | Rybelsus;
  • (LB) Lebanon: Ozempic;
  • (LT) Lithuania: Rybelsus;
  • (LU) Luxembourg: Ozempic | Rybelsus;
  • (LV) Latvia: Ozempic | Rybelsus | Wegovy;
  • (MX) Mexico: Ozempic | Rybelsus | Wegovy;
  • (MY) Malaysia: Ozempic | Rybelsus;
  • (NL) Netherlands: Ozempic | Rybelsus | Wegovy | Wegovy flextouch;
  • (NO) Norway: Ozempic | Rybelsus | Wegovy flextouch;
  • (PH) Philippines: Ozempic;
  • (PL) Poland: Ozempic | Rybelsus | Wegovy;
  • (PR) Puerto Rico: Ozempic | Rybelsus;
  • (PT) Portugal: Ozempic;
  • (QA) Qatar: Ozempic (0.25 mg Dose) | Ozempic (0.5 mg Dose) | Ozempic (1 mg Dose) | Rybelsus | Wegovy | Wegovy FlexTouch;
  • (RO) Romania: Ozempic | Rybelsus | Wegovy;
  • (RU) Russian Federation: Ozempic;
  • (SA) Saudi Arabia: Ozempic;
  • (SE) Sweden: Ozempic | Rybelsus | Wegovy flextouch;
  • (SI) Slovenia: Ozempic | Rybelsus;
  • (SK) Slovakia: Ozempic | Rybelsus;
  • (TH) Thailand: Rybelsus;
  • (TW) Taiwan: Ozempic | Rybelsus;
  • (UA) Ukraine: Ozempic;
  • (VE) Venezuela, Bolivarian Republic of: Orsema;
  • (ZA) South Africa: Ozempic | Rybelsus
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