What Is Semaglutide?

A factual reference · Last reviewed by the OPTML clinical team on April 20, 2026

Drug Class and Mechanism

Semaglutide belongs to the drug class known as GLP-1 receptor agonists (also called incretin mimetics). GLP-1 is an incretin hormone released by the L-cells of the small intestine in response to food. Semaglutide binds to the GLP-1 receptor with a long half-life (~7 days), producing several effects:

• Increased glucose-dependent insulin secretion from pancreatic beta cells.
• Suppression of glucagon secretion when blood glucose is elevated.
• Delayed gastric emptying, producing prolonged satiety.
• Reduced appetite and food intake via central GLP-1 receptors in the hypothalamus.

Approved Uses

Clinical Trial Outcomes

STEP-1 (Weight Management)

In the STEP-1 trial, a 68-week randomized, double-blind, placebo-controlled study of 1,961 adults with BMI ≥30 (or ≥27 with comorbidity), once-weekly semaglutide 2.4 mg produced 14.9% average body weight reduction versus 2.4% on placebo. 86.4% of participants on branded semaglutide lost at least 5% of body weight; 50.5% lost at least 15%. Average waist circumference reduction was 13.5 cm (≈5.3 inches).

SUSTAIN Trial Program (Type 2 Diabetes)

Across the SUSTAIN trials, semaglutide consistently reduced HbA1c by 1.2-1.8% and produced modest but clinically meaningful weight loss in patients with type 2 diabetes.

SELECT Trial (Cardiovascular Outcomes)

In the SELECT trial (Lincoff AM et al., NEJM 2023) in patients with preexisting cardiovascular disease and overweight/obesity (without diabetes), semaglutide 2.4 mg reduced major adverse cardiovascular events by 20% versus placebo.

Dosing and Administration

Semaglutide is typically administered as a once-weekly subcutaneous injection in the abdomen, thigh, or upper arm. Dose is titrated upward over 16+ weeks to minimize GI side effects. Typical titration: 0.25 mg weekly × 4 weeks → 0.5 mg × 4 weeks → 1.0 mg × 4 weeks → 1.7 mg × 4 weeks → 2.4 mg maintenance.

Side Effects

The most commonly reported side effects are gastrointestinal and usually occur during dose escalation:

• Nausea (43.9% in STEP-1)
• Diarrhea (30.0%)
• Constipation (24.2%)
• Vomiting (24.8%)
• Abdominal pain (20.4%)
• Fatigue (11.2%)

Boxed warning: Semaglutide carries an FDA boxed warning for thyroid C-cell tumors based on rodent studies. It is contraindicated in patients with personal or family history of medullary thyroid carcinoma or MEN 2.

Compounded Semaglutide

"Compounded semaglutide" refers to semaglutide prepared by state-licensed 503A compounding pharmacies. The active ingredient is the same as the branded drugs, but compounded versions are not FDA-approved as finished drug products. Compounded formulations became widely accessible during the 2022-2024 shortage of branded semaglutide. FDA regulatory status for compounded GLP-1s evolves with shortage determinations; consult a licensed clinician for the current landscape.

How Semaglutide Differs from Tirzepatide

Tirzepatide (Mounjaro, Zepbound) is a dual GIP/GLP-1 receptor agonist. Semaglutide is a single GLP-1 agonist. In the SURMOUNT-5 head-to-head trial, tirzepatide produced approximately 50% more weight loss than semaglutide over 72 weeks in adults with obesity.

References

1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002.
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes. N Engl J Med. 2023;389(24):2221-2232.
3. Novo Nordisk. Ozempic (semaglutide) prescribing information. FDA label.
4. Novo Nordisk. Wegovy (semaglutide) prescribing information. FDA label.
5. Aroda VR, Rosenstock J, Terauchi Y, et al. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy. Diabetes Care. 2019;42(9):1724-1732.