Top 10 PubMed Studies on Semaglutide for Weight Loss (2026)

The pivotal STEP-1 trial randomized 1,961 adults with obesity (BMI ≥30, no diabetes) to semaglutide 2.4 mg weekly or placebo for 68 weeks. Primary outcome: −14.9% body weight vs −2.4% on placebo. Roughly half of participants on semaglutide lost ≥15% body weight. This trial established the FDA-approved Wegovy 2.4 mg dose and the modern benchmark for GLP-1 obesity efficacy.

PMID 33567185 ↗NCT03548935 ↗

STEP-2 enrolled 1,210 adults with overweight/obesity AND type 2 diabetes — a population that typically loses less weight on GLP-1s. Semaglutide 2.4 mg produced −9.6% body weight vs −3.4% on placebo. A1C dropped 1.6 percentage points, confirming dual cardiometabolic benefit. Established the case for using Wegovy (rather than Ozempic) in T2D patients seeking weight management beyond glycemic control.

PMID 33667417 ↗NCT03552757 ↗

STEP-3 paired semaglutide 2.4 mg with intensive behavioral therapy (30 visits over 68 weeks, 1,000-1,500 kcal/day diet). Semaglutide group lost −16.0% vs placebo+IBT −5.7%. Demonstrated that GLP-1s and lifestyle therapy are additive, not redundant — important for insurance prior-auth criteria that require concurrent lifestyle programs.

PMID 33625476 ↗NCT03611582 ↗

STEP-4 randomized participants who had already lost ~10.6% body weight on semaglutide 2.4 mg through a 20-week run-in. Continuing semaglutide produced an additional −7.9% weight loss; switching to placebo caused +6.9% regain. Crystallized the chronic-disease framing: stopping a GLP-1 reverses weight loss almost completely within a year, like stopping a blood-pressure med.

PMID 33755728 ↗NCT03548987 ↗

STEP-5 extended STEP-1's design to two years (104 weeks). Semaglutide 2.4 mg maintained −15.2% body weight at year 2 (vs −2.6% placebo) — answering the durability question that critics raised after STEP-1. Half of completers maintained ≥15% loss at two years. This is the longest randomized data set for semaglutide as of 2026.

PMID 36216945 ↗NCT03693430 ↗

STEP-8 was the first head-to-head between two FDA-approved GLP-1 obesity drugs. Semaglutide 2.4 mg weekly produced −15.8% body weight vs liraglutide 3.0 mg daily −6.4% at 68 weeks. Established semaglutide as the dominant GLP-1 monotherapy for obesity and effectively retired Saxenda as a first-line choice.

PMID 35015037 ↗NCT04074161 ↗

STEP-TEENS enrolled 201 adolescents aged 12-17 with obesity. Semaglutide 2.4 mg produced −16.1% BMI vs +0.6% placebo. Drove the December 2022 FDA approval of Wegovy for adolescents ≥12 — the first GLP-1 with a pediatric weight-management label, opening the pathway for state-Medicaid pediatric coverage.

PMID 36322838 ↗NCT04102189 ↗

STEP-HFpEF tested semaglutide 2.4 mg in 529 patients with heart failure with preserved ejection fraction (HFpEF) and obesity — historically a population with no effective drug therapy. Semaglutide improved KCCQ-CSS by 7.8 points (vs 2.6 placebo) and reduced body weight 13.3% more than placebo. Established a new indication framework: GLP-1s as HFpEF disease-modifying therapy, not just weight-loss drugs.

PMID 37622681 ↗NCT04788511 ↗

SELECT randomized 17,604 adults with established cardiovascular disease + obesity (no diabetes) to semaglutide 2.4 mg or placebo. Primary MACE outcome: 6.5% (sema) vs 8.0% (placebo) = 20% relative risk reduction (HR 0.80, p<0.001). This trial drove the March 2024 FDA cardiovascular-risk-reduction indication for Wegovy and is the single most consequential trial in modern obesity medicine.

PMID 37952131 ↗NCT03574597 ↗

OASIS-1 tested high-dose oral semaglutide 50 mg daily in 667 adults with obesity (no diabetes). Produced −15.1% body weight vs −2.4% placebo at 68 weeks — comparable to injectable Wegovy 2.4 mg. Filed for FDA approval as oral Wegovy in 2024 (pending). If approved, would be the first oral GLP-1 weight-loss drug, directly competing with Foundayo (orforglipron).

PMID 37385278 ↗NCT05035095 ↗