The best peptides for weight loss are the FDA-approved GLP-1 drugs: tirzepatide (Zepbound), which produced about 20.9% average weight loss in its main trial, and semaglutide (Wegovy), which produced about 15% at 2.4 mg and 18.7% at 7.2 mg.[2][1][15] Retatrutide and CagriSema look strong in late-stage trials but are not approved. Popular “fat-loss peptides” such as AOD-9604, MOTS-c and 5-amino-1MQ have no reliable human evidence.[10][11][12]
This guide sorts options into three tiers by the strength of evidence. For the full drug class, see our GLP-1 drugs hub.
Quick comparison
| Option | Status (US) | Form | Average weight loss in main trial |
|---|---|---|---|
| Tirzepatide (Zepbound) | Approved | Weekly injection | 20.9% at 15 mg, 72 weeks[2] |
| Semaglutide (Wegovy) | Approved | Weekly injection | 14.9% at 2.4 mg, 68 weeks;[1] 18.7% at 7.2 mg, 72 weeks[15] |
| Semaglutide (Wegovy tablet) | Approved | Daily pill | 13.6% at 25 mg, 64 weeks[4] |
| Orforglipron (Foundayo) | Approved (not a peptide) | Daily pill | 11.2% at top dose, 72 weeks[5] |
| Liraglutide (Saxenda, generics) | Approved | Daily injection | 8.4 kg vs 2.8 kg placebo, 56 weeks[3] |
| Retatrutide | Investigational | Weekly injection | 25.0% at 12 mg, 80 weeks[6] |
| CagriSema (cagrilintide + semaglutide) | Under FDA review | Weekly injection | 20.4%, 68 weeks[7] |
| Survodutide | Investigational | Weekly injection | 12.2% to 13.0%[8] |
| Mazdutide | Approved in China only | Weekly injection | 14.0% at 6 mg[9] |
| AOD-9604 | Not approved | Injection | No significant loss vs placebo[10] |
| MOTS-c | Not approved | Injection | Mouse data only[11] |
| 5-amino-1MQ | Not approved (not a peptide) | Oral | Mouse data only[12] |
Results come from separate trials with different populations and lengths, so they are not direct comparisons.
What counts as a weight-loss peptide?
A peptide is a short chain of amino acids, the building blocks of proteins. Many hormones that control appetite and blood sugar, including GLP-1, GIP, glucagon and amylin, are peptides. The leading weight-loss drugs are lab-made versions of these hormones, modified to last longer in the body so they can be taken once a week:
- Semaglutide and liraglutide copy GLP-1.[13]
- Tirzepatide acts on GIP and GLP-1 receptors.[14]
- Retatrutide adds the glucagon receptor to those two.[6]
- Cagrilintide copies amylin, a hormone released with insulin that promotes fullness.[7]
Not every product in this space is a peptide. Orforglipron and 5-amino-1MQ are small molecules, which is why they can be taken by mouth more easily.[5][12] “Peptide” also says nothing about safety or effectiveness: some peptides have large trials behind them, and others have only mouse studies.
Tier 1: FDA-approved options
These have large randomized trials, known side effects and FDA-approved labels. A clinician decides which fits and sets the dose.
Tirzepatide (Zepbound)
Tirzepatide acts on two hormone receptors, GIP and GLP-1. In SURMOUNT-1, adults without diabetes lost 15.0%, 19.5% and 20.9% of their weight on 5, 10 and 15 mg, versus 3.1% on placebo.[2] Zepbound is approved for weight management and obstructive sleep apnea.[14]
Semaglutide (Wegovy injection and tablet)
Semaglutide has the broadest approvals: weight management, lowering heart attack and stroke risk, and MASH liver disease.[13] STEP 1 showed 14.9% weight loss at 2.4 mg,[1] and the label now allows up to 7.2 mg weekly for adults who need more.[13] The Wegovy tablet, taken daily at 25 mg, produced 13.6% in OASIS 4.[4] See semaglutide vs tirzepatide for the head-to-head data.
Orforglipron (Foundayo)
Foundayo was approved in April 2026 as a daily pill for weight management.[17] It works on the GLP-1 receptor but is a small molecule, not a peptide. In ATTAIN-1, the top dose produced 11.2% average weight loss.[5] See our Foundayo cost guide.
Liraglutide (Saxenda and generics)
Liraglutide is an older, daily GLP-1 injection. In the SCALE trial, people lost 8.4 kg on average versus 2.8 kg on placebo.[3] It is less effective than the weekly drugs, but generic versions have made it one of the lower-cost options. Compare it in liraglutide vs semaglutide and check prices in our Saxenda cost guide.
Tier 2: investigational, with strong trial data
These have phase 3 results but are not FDA-approved. Outside clinical trials, they are not legally available in the US, and FDA has warned about unapproved versions such as retatrutide sold online.[16]
- Retatrutide (Lilly): a triple agonist of GIP, GLP-1 and glucagon receptors. TRIUMPH-1 reported 25.0% weight loss on 12 mg at 80 weeks, versus 3.9% on placebo.[6] Lilly plans to submit it to FDA in the first quarter of 2027.[20]
- CagriSema (Novo Nordisk): cagrilintide, an amylin analog, plus semaglutide. REDEFINE 1 showed 20.4% weight loss versus 3.0% on placebo.[7] Novo submitted it to FDA in December 2025; in a separate trial it did not match tirzepatide 15 mg.[19]
- Survodutide (Boehringer Ingelheim): a GLP-1 and glucagon dual agonist that produced 12.2% to 13.0% weight loss versus 5.4% on placebo in SYNCHRONIZE-1.[8]
- Mazdutide (Innovent): a GLP-1 and glucagon dual agonist approved in China in 2025, not in the US.[21] GLORY-1 showed 14.0% weight loss on 6 mg.[9]
Tier 3: unproven “weight-loss peptides”
These are widely promoted for fat loss but lack the human evidence of Tiers 1 and 2.
- AOD-9604: a fragment of growth hormone. Its largest human trial found no significant weight loss versus placebo, and development for obesity ended in 2007. FDA’s compounding advisory committee voted 0 to 12 against allowing it in December 2024.[10][22]
- MOTS-c: a peptide made by mitochondria. It prevented diet-induced obesity in mice,[11] but FDA’s 2026 evaluation found no human data for it.[18]
- 5-amino-1MQ: a small molecule, not a peptide, that blocks the enzyme NNMT. Treated obese mice lost about 5% of body weight,[12] but it has never been tested in a published human study.
How to choose
- Talk to a clinician: they will consider your weight, health conditions, other medicines and pregnancy plans.
- Consider side effects: all GLP-1 drugs commonly cause nausea, diarrhea, vomiting and constipation, and the approved ones carry a boxed warning about thyroid tumors in rodents.[13][14]
- Check coverage and cost: insurance for weight-loss drugs varies widely; manufacturer savings programs and generic liraglutide can help.
- Plan for the long term: weight usually returns after stopping, so these are typically ongoing treatments. See stopping a GLP-1.
For more on dose steps and expectations, see semaglutide weight loss results and our guide to GLP-1 patches, which explains why supplement patches are not an alternative.
