Research review · Sources checked October 29, 2026

Published February 14, 2026 · Updated October 30, 2026

Semaglutide: approvals and key trials

Semaglutide is a once-weekly GLP-1 receptor agonist approved by the FDA as Ozempic for type 2 diabetes (2017) and as Wegovy 2.4 mg for chronic weight management (June 4, 2021).[1][2]

Approved use for weight management

FDA approved Wegovy as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with a BMI of 30 or more, or 27 or more with at least one weight-related condition such as hypertension, type 2 diabetes, or dyslipidemia.[1]

STEP 1: weight loss

In STEP 1, adults with overweight or obesity and without diabetes had a mean body-weight change of −14.9% with semaglutide 2.4 mg versus −2.4% with placebo at week 68. Half of the semaglutide group (50.5%) lost 15% or more. Nausea and diarrhea were the most common adverse events.[3] For a critical read of the design, dropout, sponsor role, and weight regain after stopping, see the How much weight will you lose on Wegovy? (STEP 1 teardown).

SELECT: cardiovascular outcomes

SELECT enrolled 17,604 adults with established cardiovascular disease and overweight or obesity but no diabetes. Over a mean follow-up of 39.8 months, the primary endpoint (cardiovascular death, nonfatal heart attack, or nonfatal stroke) occurred in 6.5% on semaglutide versus 8.0% on placebo (hazard ratio 0.80; 95% CI 0.72–0.90). Adverse events led to stopping treatment in 16.6% versus 8.2%.[4] For a critical read of absolute risk, hierarchy, population limits, and safety, see the SELECT study teardown.

Frailty. A September 2026 post hoc analysis of SELECT looked at results by a frailty score built from trial data. We cover what its authors report, and its limits, in Is semaglutide safe if you’re frail or older?

Heart failure. No randomized trial has compared semaglutide with tirzepatide (Mounjaro, Zepbound) in heart failure. An observational US insurance-claims study published October 29, 2026 linked tirzepatide to fewer heart failure hospital stays than semaglutide, with no difference in deaths, in adults with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF); a study of this kind cannot show cause and effect. We cover it alongside an earlier claims study that found no clear difference and semaglutide’s STEP-HFpEF symptom trials in Zepbound vs Wegovy: heart failure (HFpEF).

Liver disease (MASH)

On August 15, 2025, FDA granted Wegovy accelerated approval for adults with metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver scarring (F2 to F3) but no cirrhosis, based on a 72-week interim biopsy analysis of the ESSENCE trial, which continues to 240 weeks.[5] In ESSENCE part 1 (800 patients, funded by Novo Nordisk), MASH resolved without worse scarring in 62.9% on semaglutide vs 34.3% on placebo, and scarring improved without worse MASH in 36.8% vs 22.4%.[6] For how that compares with Rezdiffra (resmetirom), the other approved MASH drug, see Wegovy vs Rezdiffra for fatty liver (MASH).

Compounded and unapproved versions

Compounded semaglutide is not the FDA-approved product. See the compounding enforcement explainer for FDA’s current position.

This page summarizes published research and regulatory documents. It is not medical advice and does not recommend starting, stopping, or changing any medication.