Peptides for Fat Loss: What the Trials Show

The short answer

For fat loss, one family of peptides has been tested properly: the GLP-1-based medicines, which reduce appetite and slow the stomach. They are prescription drugs with trials of thousands of people. Almost everything else sold as a fat-loss peptide has either small or failed trials, or none in people at all. This guide reports what each trial found rather than ranking products, and it gives each dose with its source: the drug's current label, or the trial that used it.

The approved GLP-1 medicines

Semaglutide (Wegovy) and tirzepatide (Zepbound) are approved for chronic weight management. In STEP 1, 1,961 adults without diabetes lost 14.9% of their weight over 68 weeks on semaglutide 2.4 mg against 2.4% on placebo.¹ In SURMOUNT-1, 2,539 adults lost 15.0%, 19.5% and 20.9% on tirzepatide 5, 10 and 15 mg over 72 weeks against 3.1% on placebo.² When the two were compared directly in SURMOUNT-5, weight fell by 20.2% with tirzepatide and 13.7% with semaglutide over 72 weeks; the trial was open label and funded by Lilly, which makes tirzepatide.³ Our semaglutide vs tirzepatide comparison covers the details.

On their current labels, Wegovy injection starts at 0.25 mg once a week and steps up every four weeks, through 0.5, 1 and 1.7 mg, to a maintenance dose of 2.4 mg or 1.7 mg; adults who have tolerated 2.4 mg for at least four weeks can go up to 7.2 mg. Wegovy tablets start at 1.5 mg a day and step up every 30 days to 25 mg.⁴ Zepbound starts at 2.5 mg once a week for four weeks, a dose meant only for getting started, then rises in 2.5 mg steps at least four weeks apart to 5, 10 or 15 mg.⁵ The slow climb is there to limit the gut side effects, and the prescriber sets the dose.

Weight is a surrogate. In SELECT, 17,604 adults with cardiovascular disease and overweight or obesity but no diabetes took semaglutide 2.4 mg or placebo for a mean of 40 months; cardiovascular death, heart attack or stroke occurred in 6.5% against 8.0%.⁶

The side effects are mostly gastrointestinal: nausea affected 44% on Wegovy against 16% on placebo, and 25 to 29% on Zepbound against 8%.^4,5 And the effect lasts only while the drug is taken. People who stopped semaglutide after 68 weeks regained two-thirds of the weight they had lost within a year,⁷ and people switched from tirzepatide to placebo regained 14.0% of their body weight over the following year while those who continued lost a further 5.5%.⁸

Foundayo (orforglipron), approved in 2026, is a once-daily GLP-1 pill, but it is a small molecule, not a peptide.⁹ Its label starts at 0.8 mg a day and steps up, at least 30 days apart, to 2.5 mg and then 5.5 mg, with 9, 14.5 and 17.2 mg as further steps; 17.2 mg is the maximum.⁹ In its 72-week trial in 3,127 adults, weight fell 7.5%, 8.4% and 11.2% on the three doses against 2.1% on placebo.¹⁰

Large trials, not yet approved

Retatrutide, which activates GLP-1, GIP and glucagon receptors, was injected once a week at 1, 4, 8 or 12 mg in a phase 2 trial, with the higher doses started at 2 or 4 mg; 12 mg, started at 2 mg, produced 24.2% weight loss at 48 weeks, and starting at 2 mg rather than 4 mg partly eased the gut side effects.¹¹ CagriSema, semaglutide 2.4 mg combined with 2.4 mg of the amylin analogue cagrilintide, gave 20.4% weight loss against 3.0% on placebo over 68 weeks in its 3,417-person phase 3 trial, counting everyone randomised.¹² Survodutide, a glucagon and GLP-1 dual agonist injected once a week at doses raised to 3.6 mg or 6.0 mg, gave 12.2% and 13.0% against 5.4% on placebo over 76 weeks in its phase 3 trial, with gastrointestinal events in most people on the drug.¹³ None of the three is approved in the US as of September 30, 2026: Drugs@FDA lists no application for any of them.¹⁴ The doses above are the trials' regimens; none of the three has a label, so none has an approved dose.

The growth hormone route

Tesamorelin is approved, but only to reduce excess abdominal fat in adults with HIV-associated lipodystrophy. In two phase 3 trials of 806 patients, 2 mg injected under the skin daily cut visceral fat by 15.4% more than placebo over 26 weeks without changing fat under the skin,¹⁵ and people switched to placebo regained the visceral fat.¹⁶ Today's labels give 1.4 mg once a day for EGRIFTA SV and 1.28 mg once a day for EGRIFTA WR, two formulations with different doses.^17,18

AOD-9604, a fragment of growth hormone designed to break down fat, reduced weight gain in obese rodents, but its developer's summary of six human trials reports that a 24-week trial in 536 adults found no significant weight loss.¹⁹ It was never approved.

MK-677, an oral ghrelin mimetic that is not a peptide, did the opposite of fat loss in older adults: taken at 25 mg by mouth once a day, over two years it added 2.7 kg of body weight against 0.8 kg on placebo and increased limb fat.²⁰ CJC-1295 raised growth hormone and IGF-1 for days after single injections under the skin in healthy adults, and its trial found it best tolerated at 30 or 60 micrograms per kilogram,²¹ but it has never been tested for fat loss, and FDA reports serious adverse events associated with it.²² Ipamorelin has no fat-loss trial either.

Other compounds sold for fat loss

Tesofensine is a small molecule, not a peptide. In a 24-week phase 2 trial in 203 adults on a diet, taking 0.25, 0.5 or 1.0 mg once a day, weight fell 4.5%, 9.2% and 10.6% more than on placebo, and heart rate rose by 7.4 beats a minute at the middle dose.²³ It is not approved in the US. MOTS-c prevented diet-induced obesity in mice,²⁴ but it has never been given to people in a published trial.

Grey-market versions

Semaglutide and retatrutide are also sold online as "research chemicals". FDA has issued warning letters to sellers of both under that label.²⁵ When researchers placed test orders with online sellers of semaglutide without a prescription, some products held a different amount of drug from what the label said.²⁶ Even legitimately compounded semaglutide has caused harm through dosing errors, which FDA has warned about.²⁷ Our GLP-1 microdosing guide and the retatrutide hub cover these products, as of September 30, 2026.

Frequently asked questions

What is the most effective peptide for fat loss?

In trials, the GLP-1-based medicines. Tirzepatide produced up to 20.9% weight loss over 72 weeks against 3.1% on placebo, and 20.2% against 13.7% for semaglutide in a direct comparison. Both are prescription drugs.

Does the weight come back after stopping?

Mostly, yes. People who stopped semaglutide regained two-thirds of their lost weight within a year, and people switched from tirzepatide to placebo regained 14% of their body weight over the following year.

Is retatrutide approved?

No. It produced 24.2% weight loss at 48 weeks in a phase 2 trial, but as of September 30, 2026 FDA's Drugs@FDA database lists no application for it.

Does AOD-9604 work for fat loss?

Not in people. It reduced weight gain in obese rodents, but a 24-week trial in 536 adults found no significant weight loss, and it was never approved.

Do CJC-1295 or ipamorelin burn fat?

They have never been tested for fat loss in a published trial. CJC-1295 raised growth hormone and IGF-1 in healthy adults, and FDA has reported serious adverse events with it.

Related on Grey Peptides

• Semaglutide vs tirzepatide
• GLP-1 microdosing evidence
• Retatrutide hub
• AOD-9604 encyclopedia entry
• Tesamorelin encyclopedia entry
• Peptide side effects

Sources

1. Wilding, J. P. H. et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384(11), 989–1002. PMID: 33567185
2. Jastreboff, A. M. et al. (2022). Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine, 387(3), 205–216. PMID: 35658024
3. Aronne, L. J. et al. (2025). Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. New England Journal of Medicine, 393(1), 26-36. PMID: 40353578 · doi:10.1056/NEJMoa2416394
4. Novo Nordisk. WEGOVY (semaglutide) injection and tablets, US prescribing information: section 2 (injection 0.25 mg weekly, stepped every 4 weeks to 1.7 or 2.4 mg, maximum 7.2 mg for weight reduction; tablets 1.5 mg daily, stepped every 30 days to 25 mg), section 6 (nausea 44% vs 16% placebo; most common adverse reactions) and section 5 (warnings; renal and gallbladder monitoring). DailyMed version 19 of June 30, 2026, read September 30, 2026.
5. Eli Lilly and Company. ZEPBOUND (tirzepatide) injection, US prescribing information: section 2 (2.5 mg weekly for 4 weeks to start, then 2.5 mg steps at least 4 weeks apart; maintenance 5, 10 or 15 mg), section 6 (nausea 25-29% vs 8% placebo; most common adverse reactions) and section 5 (warnings). DailyMed version 40 of September 2, 2026, read September 30, 2026.
6. Lincoff, A. M. et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 389(24), 2221-2232. PMID: 37952131 · doi:10.1056/NEJMoa2307563
7. Wilding, J. P. H. et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism, 24(8), 1553-1564. PMID: 35441470 · doi:10.1111/dom.14725
8. Aronne, L. J. et al. (2024). Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 331(1), 38-48. PMID: 38078870 · doi:10.1001/jama.2023.24945
9. Eli Lilly and Company. FOUNDAYO (orforglipron) tablets, US prescribing information: a GLP-1 receptor agonist tablet taken once daily; initial US approval 2026; section 2 (0.8 mg daily, then 2.5 mg and 5.5 mg at least 30 days apart; 9, 14.5 and 17.2 mg as further steps; maximum 17.2 mg). DailyMed version 10, effective July 29, 2026, read September 30, 2026.
10. Wharton, S. et al. (2025). Orforglipron, an Oral Small-Molecule GLP-1 Receptor Agonist for Obesity Treatment. New England Journal of Medicine, 393(18), 1796-1806. PMID: 40960239
11. Jastreboff, A. M. et al. (2023). Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. New England Journal of Medicine, 389(6), 514–526. PMID: 37366315
12. Garvey, W. T. et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 393(7), 635-647. PMID: 40544433 · doi:10.1056/NEJMoa2502081
13. le Roux, C. W. et al. (2026). Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med, 395(8), 776-787. PMID: 42253238 · doi:10.1056/NEJMoa2600751
14. U.S. Food and Drug Administration. Drugs@FDA (openFDA): no application listed for retatrutide, cagrilintide (CagriSema) or survodutide; orforglipron listed as FOUNDAYO, NDA 220934. Read September 30, 2026.
15. Falutz, J. et al. (2010). Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab, 95(9), 4291-304. PMID: 20554713 · doi:10.1210/jc.2010-0490
16. Falutz, J. et al. (2008). Long-term safety and effects of tesamorelin, a growth hormone-releasing factor analogue, in HIV patients with abdominal fat accumulation. AIDS, 22(14), 1719-28. PMID: 18690162 · doi:10.1097/QAD.0b013e32830a5058
17. Theratechnologies. EGRIFTA SV (tesamorelin) for injection, US prescribing information: section 2 (1.4 mg under the skin once daily; applies only to the 2 mg vial). DailyMed version 9, effective July 29, 2026, read September 30, 2026.
18. Theratechnologies. EGRIFTA WR (tesamorelin) for injection, US prescribing information: section 2 (1.28 mg under the skin once daily; applies only to the 11.6 mg vial). DailyMed version 2, effective July 29, 2026, read September 30, 2026.
19. Stier, H. et al. (2013). Safety and tolerability of the hexadecapeptide AOD9604 in humans. Journal of Endocrinology and Metabolism, 3(1-2), 7-15 (not PubMed-indexed; read in full September 27, 2026). doi:10.4021/jem157w
20. Nass, R. et al. (2008). Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Ann Intern Med, 149(9), 601-11. PMID: 18981485
21. Teichman, S. L. et al. (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab, 91(3), 799-805. PMID: 16352683
22. U.S. Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks: CJC-1295 (serious adverse events including increased heart rate and systemic vasodilatory reaction; clinical data limited). Content current as of April 22, 2026; read September 30, 2026. FDA
23. Astrup, A. et al. (2008). Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet, 372(9653), 1906-1913. PMID: 18950853 · doi:10.1016/S0140-6736(08)61525-1
24. Lee, C. et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab, 21(3), 443-54. PMID: 25738459 · doi:10.1016/j.cmet.2015.02.009
25. U.S. Food and Drug Administration (December 10, 2024). Warning letter 695663: semaglutide and retatrutide sold as research chemicals only. FDA warning letter
26. Ashraf, A. R. et al. (2024). Multifactor quality and safety analysis of semaglutide products sold by online sellers without a prescription: market surveillance, content analysis, and product purchase evaluation study. Journal of Medical Internet Research, 26, e65440. PMID: 39509151
27. U.S. Food and Drug Administration. FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products (July 26, 2024). Read September 30, 2026. FDA

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Grey-market products are not the drugs the trials tested.