Obesity and Weight Management: Peptide Medicine Evidence
Trial evidence for approved peptide weight-management medicines (semaglutide, tirzepatide), their label warnings, and why promoted or compounded "weight loss peptides" are a different story.
Content last updated . This page has not been medically reviewed.
What the US labels say
- Wegovy (semaglutide): with diet and activity, to reduce excess body weight and maintain the loss in adults and children 12 and older with obesity, and in adults with overweight plus a weight-related condition; also to reduce major heart events in adults with established heart disease and obesity or overweight. [1]
- Zepbound (tirzepatide): to reduce excess body weight and maintain the loss in adults with obesity, or overweight plus a weight-related condition, and to treat moderate to severe obstructive sleep apnea in adults with obesity. [2]
- Both labels carry a boxed warning about thyroid C-cell tumors seen in rodents, with unknown relevance in humans, and are contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. [1][2]
- The Zepbound label says use with other tirzepatide products or any GLP-1 receptor agonist is not recommended. [2]
Medicine overviews: semaglutide and tirzepatide. For general weight information and medical care, see the Wellness guide to weight-loss medications and medical care.
Evidence, trial by trial
| Pairing | Population and design | Size, comparator, length | Result | Adverse events and limits | Funding |
|---|---|---|---|---|---|
| Semaglutide vs placebo (STEP 1) | Adults with obesity, or overweight plus a condition, without diabetes; double-blind, with lifestyle support [3] | 1,961 people, 2 to 1 split; 68 weeks [3] | Body weight change -14.9% vs -2.4%; 86.4% vs 31.5% lost at least 5% [3] | Weight regained after stopping (see below) | Authors include Novo Nordisk employees [3] |
| Tirzepatide vs placebo (SURMOUNT-1) | Adults with obesity or overweight plus a complication, without diabetes; double-blind [4] | 2,539 people; three tirzepatide groups and placebo; 72 weeks [4] | Weight change -15.0%, -19.5% and -20.9% vs -3.1% [4] | Mostly stomach effects, mainly during dose increases; stopped for adverse events in 2.6% of the placebo group and 4.3% to 7.1% of the tirzepatide groups [4] | Eli Lilly [4] |
| Tirzepatide vs semaglutide (SURMOUNT-5) | Adults with obesity, no type 2 diabetes; open-label [5] | 751 people; maximum tolerated dose of each; 72 weeks [5] | Weight change -20.2% vs -13.7%; waist circumference also fell more [5] | Stomach effects in both groups; open-label design [5] | Eli Lilly [5] |
| Semaglutide, after treatment ended (STEP 1 extension) | Subset of STEP 1 completers followed off treatment; exploratory [6] | 327 people; one year after stopping [6] | Regained about two-thirds of prior weight loss; heart and metabolic markers drifted back toward baseline [6] | Exploratory analysis in a subset of sites [6] | Authors include Novo Nordisk employees [6] |
The extension result matters for expectations: the authors concluded that ongoing treatment appears to be needed to keep the benefit. [6] Whether to continue is a decision for the person and the prescriber.
Comparing drugs across many trials
A 2026 BMJ network meta-analysis pooled 262 trials with 99,791 participants and 19 drugs. At one year, tirzepatide showed the largest average weight loss (about 14.9% vs lifestyle alone) and subcutaneous semaglutide about 9.8%. Tirzepatide also reduced fat mass the most but lean mass the most too (about 8.3%). The authors concluded that larger benefits generally came with greater harms and more people stopping treatment, that most agents did not meaningfully improve quality of life, and that few showed cardiovascular benefit. [7] See the cardiovascular outcomes page for the trials behind heart claims.Promoted and compounded "weight loss peptides"
AOD-9604. This is a fragment of growth hormone promoted for fat loss. The World Anti-Doping Agency's 2026 list names it as a prohibited growth hormone fragment. [8] On its category 2 page (content current as of 04/22/2026) the FDA lists AOD-9604 among substances nominated for compounding and then withdrawn, and says it has identified serious adverse events that may be associated with it, though causality is not clear. [9] In a PubMed search on 2026-10-22 we found no peer-reviewed human efficacy trial for obesity among the results, which were reviews and older papers; that does not prove none exists. [10] Evidence label: insufficient evidence. See the AOD-9604 page.BPC-157 and weight. The leading PubMed results for BPC-157 with weight or glucose terms were animal papers and reviews, with no controlled human weight trial. [11]
Compounded semaglutide or tirzepatide. The FDA says compounded GLP-1 drugs are not FDA approved and are not reviewed for safety, effectiveness or quality before marketing. It also says retatrutide and cagrilintide cannot be used in compounding under federal law and are not components of FDA-approved drugs. [12] A Colorado survey of 93 business websites found 41 referred to FDA approval when describing compounded products, and one advertised a product combined with BPC-157. [13] This is a marketing and regulation problem, not evidence of benefit.
Frequently asked questions
Do all peptides cause weight loss?
No. Semaglutide and tirzepatide are specific, approved molecules with trial data. Most other peptides marketed for weight have no good human trials. Evidence label: insufficient evidence or marketing claim.
Is tirzepatide stronger than semaglutide?
In SURMOUNT-5, a 72-week open-label trial funded by Eli Lilly in adults with obesity and without diabetes, average weight loss was larger with tirzepatide. [5] A single trial cannot say which suits an individual, and side effects differ.
What happens when treatment stops?
In the STEP 1 extension, people regained about two-thirds of the weight they had lost within a year of stopping semaglutide and lifestyle support. [6] Talk with the prescriber before changing any treatment.
Are compounded versions the same as the approved brands?
Not necessarily. The FDA says compounded drugs are not reviewed for safety, effectiveness or quality, and lists red flags such as claims that a compounded drug is the same as an approved one. [12]
Is AOD-9604 approved for weight loss?
The sources we read show no approval. The FDA page lists it among withdrawn compounding nominations, and WADA lists it as prohibited in sport. [9][8] Evidence is insufficient.
More details: evidence, limits and cautions
The details behind this page: cautions, limits of the evidence and where sources disagree. Open any note to read it.
How to read the evidence labels
Labels used on this page: approved medicine (regulator and use named), established (large trials agree), mixed, insufficient evidence, preclinical (cells or animals only), evidence of harm and marketing claim. Proper evidence not found means we looked and found no usable human study. Labels were read from DailyMed on 2026-10-22 and cover the US only.
Safety information
References
- U.S. National Library of Medicine, DailyMed. WEGOVY (semaglutide) injection and tablets, FDA prescribing information (DailyMed listing, revised 6/2026). Read 2026-10-22.
- U.S. National Library of Medicine, DailyMed. ZEPBOUND (tirzepatide) injection, FDA prescribing information (DailyMed listing, revised 8/2026). Read 2026-10-22.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021;384:989-1002 (STEP 1). Read 2026-10-22.
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205-216 (SURMOUNT-1). Read 2026-10-22.
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med 2025;393:26-36 (SURMOUNT-5). Read 2026-10-22.
- Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab 2022;24:1553-1564. Read 2026-10-22.
- Comparative effects of drugs for adults with overweight or obesity: systematic review and network meta-analysis. BMJ 2026;394:e372161. Read 2026-10-22.
- World Anti-Doping Agency. 2026 Prohibited List (in effect 1 January 2026). Read 2026-10-22.
- U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks (content current as of 04/22/2026). Read 2026-10-22.
- U.S. National Library of Medicine. PubMed search: (AOD9604 OR AOD-9604) AND (obesity OR weight). Search run 2026-10-22; result titles read.
- U.S. National Library of Medicine. PubMed search: (BPC-157 OR BPC157) AND (diabetes OR glucose OR obesity OR weight). Search run 2026-10-22; result titles read.
- U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss (content current as of 10/01/2026). Read 2026-10-22.
- Compounded glucagon-like peptide-1 receptor agonists for weight loss: the direct-to-consumer market in Colorado. J Pharm Policy Pract 2024;18:2441220. Read 2026-10-22.