Semaglutide

The landmark STEP 1 trial studied once-weekly semaglutide 2.4 mg in adults with overweight or obesity without diabetes. At 68 weeks, participants receiving semaglutide experienced substantially greater weight reduction than those receiving placebo.

More participants receiving semaglutide achieved at least 5% weight loss (86.4% vs. 31.5%), at least 10% (69.1% vs. 12.0%), and at least 15% (50.5% vs. 4.9%). Average absolute weight change was approximately −15.3 kg with semaglutide versus −2.6 kg with placebo. This represents strong randomized human evidence for semaglutide's role in chronic weight management.

Wegovy® is FDA-approved to reduce excess body weight and maintain weight reduction long term in qualifying adults with obesity or overweight. Injectable Wegovy is also approved for adolescents age 12 years and older with obesity.

Semaglutide therefore differs substantially from experimental peptides promoted for fat loss without an established FDA-approved weight-management indication.

The SELECT trial enrolled 17,604 adults with overweight or obesity and established cardiovascular disease who did not have diabetes. Major cardiovascular events occurred in 6.5% receiving semaglutide versus 8.0% receiving placebo. The hazard ratio was 0.80, representing a 20% relative reduction in the primary cardiovascular endpoint.

On March 8, 2024, FDA approved Wegovy to reduce the risk of cardiovascular death, nonfatal heart attack, and nonfatal stroke in adults with established cardiovascular disease and obesity or overweight.

This is an important distinction: semaglutide is not only a weight-management medication. In a specific high-risk population, cardiovascular-risk reduction is an FDA-approved use.

Semaglutide is also FDA-approved under Ozempic® and oral semaglutide formulations for treatment of type 2 diabetes. Current Ozempic labeling includes use alongside diet and exercise to improve glycemic control in adults with type 2 diabetes.

Semaglutide stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner, helping improve blood-glucose regulation.

The FLOW trial enrolled 3,533 participants with type 2 diabetes and chronic kidney disease. Semaglutide reduced the risk of the composite major kidney outcome by approximately 24% compared with placebo. The primary endpoint included outcomes such as kidney failure, a sustained ≥50% reduction in kidney filtration, kidney-related death, and cardiovascular death. The hazard ratio was 0.76.

Current FDA labeling for Ozempic therefore includes reducing the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease. This is a major expansion of semaglutide's established medical evidence beyond glucose control and weight management.

Another major development occurred on August 15, 2025. FDA granted accelerated approval to Wegovy injection for adults with noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced liver fibrosis, stages F2–F3.

The approval was based on interim results from the Phase 3 ESSENCE trial. At 72 weeks, MASH resolution without worsening fibrosis occurred in 63% with Wegovy versus 34% with placebo, and improvement in liver fibrosis without worsening MASH occurred in 37% with Wegovy versus 22% with placebo.

This indication received accelerated approval, meaning continued approval may depend on confirmation of longer-term clinical benefits in the ongoing trial.

Semaglutide has also been studied in adolescents. In the STEP TEENS trial, 73% of adolescents receiving semaglutide achieved at least 5% weight loss compared with 18% receiving placebo. Semaglutide also improved several cardiometabolic measures.

This research contributed to injectable Wegovy's FDA-approved use in adolescents age 12 and older with obesity.

Semaglutide does not necessarily have to be injectable. The Phase 3 OASIS 1 trial examined daily oral semaglutide in adults with overweight or obesity without diabetes. At week 68, estimated average body-weight change was −15.1% with oral semaglutide versus −2.4% with placebo, and approximately 85% of treated participants achieved at least 5% weight reduction.

Since then, FDA labeling has expanded to include Wegovy tablets for adult weight reduction and cardiovascular-risk reduction, with a current maintenance dose of 25 mg orally once daily.