Short answer: Three drugs are FDA approved for weight management: Wegovy (semaglutide), Zepbound (tirzepatide) and Saxenda (liraglutide). In their main trials, average weight loss was about 15% to 21% for the weekly drugs and 8 kg for daily liraglutide. Retatrutide and CagriSema have large trials but no approval yet. AOD-9604 showed safety data but no published weight benefit, and MOTS-c has only mouse data.
| Compound | Best evidence | What it shows |
|---|---|---|
| Semaglutide (Wegovy) | FDA-approved for this | In STEP 1 (1,961 adults, 68 weeks), weight fell 14.9% on average versus 2.4% on placebo. |
| Tirzepatide (Zepbound) | FDA-approved for this | In SURMOUNT-1 (2,539 adults, 72 weeks), weight fell 15.0%, 19.5% and 20.9% on 5, 10 and 15 mg versus 3.1% on placebo. |
| Liraglutide (Saxenda) | FDA-approved for this | In SCALE (3,731 adults, 56 weeks), weight fell 8.4 kg on daily liraglutide 3.0 mg versus 2.8 kg on placebo. |
| Retatrutide | Human trials | In a phase 2 trial (338 adults, 48 weeks), weight fell 24.2% on the 12 mg arm versus 2.1% on placebo. Not FDA approved as of October 2026. |
| Cagrilintide with semaglutide (CagriSema) | Human trials | In REDEFINE 1 (3,417 adults, 68 weeks), weight fell 20.4% versus 3.0% on placebo. Not FDA approved as of October 2026. |
| AOD-9604 | Small or early human studies | A company-authored pooled safety report of six placebo-controlled trials found no change in IGF-1 or glucose tolerance. It reports no weight-loss result. |
| MOTS-c | Animal or lab studies only | Prevented diet-induced obesity and insulin resistance in mice (2015). FDA says it has found no human exposure data. |
"Animal or lab studies only" means no published human trial for this goal that we could find. Results in rats or cells often do not carry over to people. Compounds that are not FDA-approved have no tested label for dose, purity or safety.
The approved drugs are GLP-1 receptor agonists, meaning they copy a gut hormone that slows the stomach and lowers appetite. Tirzepatide also acts on a second hormone receptor (GIP). Every trial below added the drug to diet and exercise advice, and the placebo groups got the same advice.
| Drug and trial | People, length | Drug | Placebo |
|---|---|---|---|
| Semaglutide 2.4 mg weekly, STEP 1 | 1,961 adults, 68 weeks | -14.9% | -2.4% |
| Tirzepatide 5 / 10 / 15 mg weekly, SURMOUNT-1 | 2,539 adults, 72 weeks | -15.0% / -19.5% / -20.9% | -3.1% |
| Liraglutide 3.0 mg daily, SCALE | 3,731 adults, 56 weeks | -8.4 kg | -2.8 kg |
| Retatrutide 12 mg weekly, phase 2 | 338 adults, 48 weeks | -24.2% | -2.1% |
| CagriSema weekly, REDEFINE 1 | 3,417 adults, 68 weeks | -20.4% | -3.0% |
| CagriSema weekly, REDEFINE 2 (type 2 diabetes) | 1,206 adults, 68 weeks | -13.7% | -3.4% |
Averages hide a wide spread. In STEP 1, 86.4% of people on semaglutide lost at least 5% of their weight and 50.5% lost at least 15%. In SURMOUNT-1, 57% on the 15 mg dose lost at least 20%. Some people lost much less.
Trials are not directly comparable: they enrolled different people over different lengths of time. For a head-to-head look at the two most used drugs, see semaglutide vs tirzepatide.
The Wegovy and Zepbound labels cover adults with obesity, or adults with overweight plus at least one weight-related condition, used with a reduced-calorie diet and more physical activity. Wegovy and Saxenda are also approved for children 12 and older with obesity; the Saxenda label adds a body weight above 60 kg. Wegovy also carries an indication to lower the risk of heart attack, stroke and heart-related death in adults with heart disease and obesity or overweight. Zepbound is also approved for moderate to severe obstructive sleep apnea in adults with obesity.
All three labels say not to combine them with another GLP-1 drug. Brand guides: Wegovy, Zepbound, Saxenda.
Terms on this page: GLP-1 receptor agonist · GIP (glucose-dependent insulinotropic polypeptide) · Amylin analog · Titration (dose escalation)