Weight-loss peptides compared
Three once-weekly peptides have large obesity trials. Semaglutide (GLP-1) showed −14.9% average weight change, tirzepatide (GIP and GLP-1) −20.9%, and retatrutide (GIP, GLP-1 and glucagon) −25.0% on their top doses. Semaglutide and tirzepatide are FDA-approved; retatrutide is not. Only semaglutide and tirzepatide have been compared head to head.[1,2,3,4]
8 sources, every number linked. PepDose sells no peptides and takes no vendor money.
At a glance
How do they compare?
Each column's placebo-controlled result comes from a different trial, so the gaps between them are a rough guide. The one direct comparison is SURMOUNT-5 (tirzepatide against semaglutide), shown in its own row.
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Receptors | SemaglutideGLP-1 | TirzepatideGIP and GLP-1 | RetatrutideGIP, GLP-1 and glucagon |
| FDA status[5,6,3] | SemaglutideApproved (Wegovy, Ozempic) | TirzepatideApproved (Zepbound, Mounjaro) | RetatrutideNot approved |
| Main obesity trial[1,2,3] | SemaglutideSTEP 1: 1,961 adults, 68 weeks | TirzepatideSURMOUNT-1: 2,539 adults, 72 weeks | RetatrutideTRIUMPH-1: 2,339 adults, 80 weeks |
| Weight change on the top dose[1,2,3] | Semaglutide−14.9% on 2.4 mg | Tirzepatide−20.9% on 15 mg | Retatrutide−25.0% on 12 mg |
| Placebo in the same trial[1,2,3] | Semaglutide−2.4% | Tirzepatide−3.1% | Retatrutide−3.9% |
| Head to head (SURMOUNT-5, 72 weeks)[4] | Semaglutide−13.7% | Tirzepatide−20.2% | RetatrutideNot tested |
| Stopped because of side effects[1,2,7] | Semaglutide4.5% for stomach side effects (STEP 1) | Tirzepatide4.3% to 7.1% (SURMOUNT-1) | Retatrutide4% to 12% (TRIUMPH-2) |
| Heart-outcome trial[8] | SemaglutideSELECT: 20% lower risk | TirzepatideNone among our sources | RetatrutideNone published |
Receptors
Which receptors does each one act on?
Tap a drug to compare. Each extra receptor adds another hormone signal. More receptors does not by itself mean safer or better.
Which peptide leads to the most weight loss?
In their own phase 3 trials, retatrutide showed the largest average weight change (−25.0% at 80 weeks), then tirzepatide (−20.9% at 72 weeks), then semaglutide (−14.9% at 68 weeks). Only tirzepatide and semaglutide have been compared directly: −20.2% versus −13.7% in SURMOUNT-5.[3,2,1,4]
Which weight-loss peptides are FDA-approved?
Semaglutide and tirzepatide. Semaglutide is approved for weight management as Wegovy (2021) and tirzepatide as Zepbound (2023). Retatrutide is not approved for any use; its phase 3 results were published in September 2026. Research powders of any of them are not the approved medicines.[5,6,3]
Do more receptors mean a better drug?
Not by itself. Semaglutide acts on one receptor, tirzepatide on two and retatrutide on three, and average weight change rose in that order across their separate trials. But each extra receptor adds another hormone signal, and retatrutide's trials also reported low blood pressure and unusual skin sensations.[1,2,3,7]
What side effects do they share?
Stomach and gut effects. Nausea and diarrhea were among the most common side effects in the semaglutide, tirzepatide and retatrutide trials. In the obesity trials cited here, between about 4% and 12% of people stopped treatment because of side effects, depending on the drug, dose and trial.[1,2,7]
Work out the units for your vial
Milligrams are not comparable between compounds, and the units on your syringe depend on your vial and how much water you add. Each guide has a chart for its common vial sizes.
Questions
Common questions
Is tesamorelin a weight-loss peptide?
No. Tesamorelin's FDA label says it is not for weight loss. In trials it reduced visceral (deep belly) fat in people with HIV-associated lipodystrophy, but its effect on overall body weight was neutral.
Which weight-loss peptide has heart-outcome data?
Semaglutide. In SELECT (17,604 adults with heart disease and overweight or obesity), 2.4 mg weekly cut the risk of heart attack, stroke or cardiovascular death by 20% over about 40 months.
Are these peptides taken daily or weekly?
All three were given as one injection under the skin per week in their trials.
Can the trial results be compared directly?
Only SURMOUNT-5 can, because it put tirzepatide and semaglutide in the same trial. The other numbers come from separate trials with different participants and lengths (68, 72 and 80 weeks), so they are a rough guide.
Sources
- 1.Once-weekly semaglutide in adults with overweight or obesity (STEP 1)
Wilding JPH et al. N Engl J Med 2021;384:989-1002 · Human trial - 2.Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)
Jastreboff AM et al. N Engl J Med 2022;387:205-216 · Human trial - 3.Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1)
Jastreboff AM et al. N Engl J Med 2026 (online Sep 29) · Human trial - 4.Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5)
Aronne LJ et al. N Engl J Med 2025;393:26-36 · Human trial - 5.Wegovy approval letter
FDA. Wegovy (semaglutide) NDA 215256 approval letter, June 2021 · FDA - 6.Zepbound label
FDA. Zepbound (tirzepatide) prescribing information, 2024 · FDA - 7.Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2)
Bellido V et al. Lancet 2026 (online Sep 29) · Human trial - 8.Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT)
Lincoff AM et al. N Engl J Med 2023;389:2221-2232 · Human trial
Last reviewed Oct 4, 2026. Education only, not medical advice. PepDose sells no peptides.