The 10 Semaglutide Weight-Loss Trials That Matter (2026)

The trial everything else is measured against. 1,961 adults carrying obesity without diabetes, given weekly semaglutide 2.4 mg against placebo across 68 weeks, and the result was −14.9% against −2.4%. Just over half the treated group lost at least 15% of their body weight, where one in twenty did on placebo. This is where the Wegovy 2.4 mg dose comes from, and it reset what counts as a good result in obesity medicine.

PMID 33567185 ↗NCT03548935 ↗

The same design run in 1,210 people who also had type 2 diabetes — a group that consistently loses less weight on these drugs, for reasons that are still argued about. Semaglutide delivered −9.6% against −3.4%, roughly two-thirds of what STEP-1 achieved, alongside a 1.6-point fall in A1C. The practical upshot is that diabetes blunts the effect without abolishing it, which is why the same person may be a candidate for the weight-labeled product rather than the diabetes-labeled one.

PMID 33667417 ↗NCT03552757 ↗

The question here was whether the drug and serious behavioral therapy overlap or add. Everyone got the intensive program — 30 visits and a 1,000 to 1,500 calorie diet — and half also got semaglutide. The drug arm lost 16.0%, the therapy-only arm 5.7%. They add. That finding does real work in the insurance argument, because prior-authorization criteria routinely demand a concurrent lifestyle program, and this is the evidence that the requirement is not merely bureaucratic.

PMID 33625476 ↗NCT03611582 ↗

The withdrawal trial, and the most quietly important one on this list. Participants first spent 20 weeks getting to the full dose, losing about 10.6% along the way. Then half kept going and half switched to placebo. The continuers lost a further 7.9%. The switchers regained 6.9%. ⛔ Almost everything gained back, inside a year, on a drug that had been working — which is the finding that makes obesity a chronic condition rather than a course of treatment.

PMID 33755728 ↗NCT03548987 ↗

STEP-1 extended to two years, answering the durability objection raised the moment the first result appeared. At 104 weeks the treated group held −15.2% against −2.6%, and half of those who completed were still down at least 15%. Nothing longer exists as randomized data for this drug, which is worth remembering whenever someone asks what happens after five years: nobody has run that trial.

PMID 36216945 ↗NCT03693430 ↗

The only head-to-head between two approved GLP-1 obesity drugs, and it was decisive. Weekly semaglutide produced −15.8% against daily liraglutide's −6.4% over 68 weeks — a gap of more than nine percentage points. Roughly seven in ten reached at least 10% loss on semaglutide against one in four on liraglutide, and more than twice as many people abandoned liraglutide. It effectively ended the case for starting anyone on the older drug.

PMID 35015037 ↗NCT04074161 ↗

201 adolescents aged 12 to 17, and the effect was, if anything, larger than in adults: −16.1% BMI against a placebo group that drifted slightly upward. This is the trial behind the FDA's December 2022 decision to extend Wegovy to children aged 12 and over — the first GLP-1 to carry a pediatric weight indication, and the opening that made state Medicaid coverage for adolescents arguable at all.

PMID 36322838 ↗NCT04102189 ↗

529 people with obesity and heart failure with preserved ejection fraction — a condition that had essentially no effective drug therapy. Semaglutide improved symptom scores by 7.8 points against 2.6 on placebo, alongside 13.3 percentage points more weight loss. The significance is conceptual as much as clinical: it is the first strong evidence that these drugs treat a disease of the heart rather than merely the weight sitting on top of it.

PMID 37622681 ↗NCT04788511 ↗

The trial that turned a weight drug into cardiovascular medicine. 17,604 adults with established heart disease and obesity but no diabetes, followed for years. Major cardiovascular events occurred in 6.5% on semaglutide against 8.0% on placebo — a hazard ratio of 0.80, meaning a fifth fewer heart attacks, strokes and cardiovascular deaths. This produced the March 2024 cardiovascular indication, and it is the reason insurers and Medicare can pay for the drug on grounds that have nothing to do with the scale. ⚠ Note the other number: 16.6% stopped it for side effects, against 8.2% on placebo.

PMID 37952131 ↗NCT03574597 ↗

The high-dose oral trial: 50 mg of semaglutide swallowed daily by 667 adults with obesity, producing −15.1% against −2.4% — a result standing comfortably alongside the injection. ★ Its status has since changed. Wegovy tablets are now approved, so this is no longer a pending application; note though that the approved tablet reaches a 25 mg maintenance dose rather than the 50 mg tested here. The oral market it was built to enter now also contains orforglipron, which is a different molecule entirely.

PMID 37385278 ↗NCT05035095 ↗