Peptides Studied for Weight Loss: What the Trials Actually Show

"Weight-loss peptides" covers two very different groups. One group has been tested in large, placebo-controlled trials with thousands of people. The other rests on a handful of mouse studies from the 1990s and 2000s. Search results often mix them together as if they were equivalent. They are not.

This guide goes through the compounds most often discussed, in order of evidence strength. For each we give what it is, the strongest level of evidence, and findings sourced to PubMed. Doses mentioned are the ones used in specific trials, not recommendations. We don't rank these by effectiveness, and trial results in one population don't transfer neatly to another.

Evidence levels used here

• Phase 3 RCT: a large randomized controlled trial (RCT), the kind used for drug approval.
• Phase 1 or 2 RCT: smaller, shorter trials focused on safety and dose-finding.
• Animal: rodent studies only.

Summary table

Approved: semaglutide and tirzepatide

Semaglutide is a once-weekly GLP-1 receptor agonist, meaning it mimics the gut hormone GLP-1. See the semaglutide page. In the STEP 1 trial, 1,961 adults with overweight or obesity (without diabetes) received 2.4 mg weekly or placebo for 68 weeks alongside lifestyle support. Mean body weight fell 14.9% with semaglutide versus 2.4% with placebo. Nausea and diarrhea were the most common side effects, and 4.5% stopped treatment because of gastrointestinal events, versus 0.8% on placebo (Wilding 2021).

Tirzepatide acts on both GLP-1 and GIP receptors (GIP is a second gut hormone). See the tirzepatide page. In SURMOUNT-1, 2,539 adults were randomized to 5, 10 or 15 mg weekly or placebo for 72 weeks. Mean weight change was -15.0%, -19.5% and -20.9% across the three doses, versus -3.1% with placebo (Jastreboff 2022). In an open-label head-to-head trial of 751 adults, weight fell 20.2% with tirzepatide and 13.7% with semaglutide at 72 weeks (Aronne 2025). For more detail, see semaglutide vs tirzepatide.

All three trials were funded by the companies developing the drugs (Novo Nordisk or Eli Lilly), which is typical for phase 3 work.

Investigational, with phase 3 data

Cagrilintide is a long-acting analogue of amylin, a pancreatic hormone that promotes fullness. See the cagrilintide page. In a 26-week phase 2 trial, cagrilintide alone produced mean weight reductions of 6.0% to 10.8% across doses, versus 3.0% with placebo (Lau 2021). Combined with semaglutide (the pairing known as CagriSema), the phase 3 REDEFINE 1 trial in 3,417 adults reported a mean change of -20.4% versus -3.0% with placebo at 68 weeks. Gastrointestinal side effects affected 79.6% of the combination group and 39.9% of the placebo group (Garvey 2025).

Mazdutide targets GLP-1 and glucagon receptors. See the mazdutide page. In the phase 3 GLORY-1 trial of 610 Chinese adults, mean weight change at 48 weeks was -11.0% (4 mg) and -14.0% (6 mg), versus +0.3% with placebo (Ji 2025). The trial enrolled only Chinese adults, with a BMI of 28 or more (or 24 or more with a weight-related condition), a lower entry threshold than STEP 1 or SURMOUNT-1.

Survodutide is another GLP-1/glucagon dual agonist. See the survodutide page. In a phase 3 trial of 725 adults, mean weight change at 76 weeks was -12.2% and -13.0% at the two doses, versus -5.4% with placebo. Gastrointestinal symptoms occurred in 80.9% and 89.7% of the survodutide groups and 47.9% of the placebo group (le Roux 2026).

Investigational, earlier stage

GLP-3 R is a single peptide that activates three receptors: GLP-1, GIP and glucagon (a "triple agonist"). The name is a product label, not the name of a hormone. See the GLP-3 R page, which also covers the larger trials. In a 12-week phase 1b trial in 72 people with type 2 diabetes (code name LY3437943), placebo-adjusted weight loss appeared dose dependent, reaching about 9 kg in the highest-dose group. Its half-life was about 6 days, and gastrointestinal events were the most frequent side effects (Urva 2022).

Petrelintide is another long-acting amylin analogue. See the petrelintide page. In two company-sponsored phase 1 trials, it had a half-life of about 10 days, and in the multiple-dose part weight fell by up to 8.6% after 16 weeks. Nausea occurred in 16.7% to 33.3% of petrelintide recipients versus 16.7% on placebo (Brændholt Olsen 2026). Phase 1 trials are small and not designed to establish efficacy.

Older compounds with weaker or compromised evidence

Tesofensine is not a peptide. It is a small-molecule drug that blocks the reuptake of noradrenaline, dopamine and serotonin. See the tesofensine page. Its key trial randomized 203 patients at five Danish centres to one of three doses or placebo for 24 weeks, with mean weight loss of 4.5%, 9.2% and 10.6% versus 2.0% on diet and placebo. Heart rate rose by 7.4 beats per minute in the 0.5 mg group (Astrup 2008). In 2013 The Lancet published an expression of concern about this paper (Lancet 2013), a formal notice that the journal has concerns about a published paper. Treat its numbers with caution.

AOD-9604 is a synthetic analogue of the lipolytic (fat-breaking) region of human growth hormone. See the AOD-9604 page. In obese rats, 19 days of oral AOD-9604 cut body-weight gain by more than half compared with controls (Ng 2000). In obese mice, it reduced weight gain and increased fat oxidation without binding the growth-hormone receptor (Heffernan 2001). We did not find a published human weight-loss trial with results in a PubMed abstract.

HGH Fragment 176-191 is a closely related growth-hormone fragment. See the HGH Fragment 176-191 page. Its evidence is older still: a synthetic hGH 177-191 peptide reduced cumulative weight gain and fat-tissue mass in obese mice (Natera 1994). Note that the studied peptide spans residues 177-191, not the 176-191 sequence usually sold. For how the two fragments differ, see AOD-9604 vs HGH Fragment 176-191.

The bottom line

The evidence gap on this list is enormous. The incretin-based drugs at the top have multiple large trials with thousands of participants, along with well-documented gastrointestinal side effects. The compounds at the bottom have rodent data, and in tesofensine's case a key human trial the publishing journal has flagged. A compound's place in this list reflects how well it has been studied, not how well it works for any individual.

Sources

• Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 2021. PMID 33567185
• Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med, 2022. PMID 35658024
• Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med, 2025. PMID 40353578
• Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lancet, 2021. PMID 34798060
• Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 2025. PMID 40544433
• Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med, 2025. PMID 40421736
• Survodutide Once Weekly for the Treatment of Adults with Obesity. N Engl J Med, 2026. PMID 42253238
• LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet, 2022. PMID 36354040
• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Petrelintide for Weight Management: Two Randomized, Controlled Phase 1 Trials. Diabetes Obes Metab, 2026. PMID 42017294
• Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet, 2008. PMID 18950853
• Expression of concern--effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet, 2013. PMID 23561987
• Metabolic studies of a synthetic lipolytic domain (AOD9604) of human growth hormone. Horm Res, 2000. PMID 11146367
• Increase of fat oxidation and weight loss in obese mice caused by chronic treatment with human growth hormone or a modified C-terminal fragment. Int J Obes Relat Metab Disord, 2001. PMID 11673763
• Reduction of cumulative body weight gain and adipose tissue mass in obese mice: response to chronic treatment with synthetic hGH 177-191 peptide. Biochem Mol Biol Int, 1994. PMID 7987248

This article is for educational and research purposes only and is not medical advice.