Peptides for weight loss: approved GLP-1 drugs vs research peptides, ranked by evidence

The best-researched peptides for weight loss are FDA-approved GLP-1 drugs: tirzepatide (Zepbound) cut body weight by 20.9% in a 2,539-person trial and semaglutide (Wegovy) by 14.9% in a 1,961-person trial. Retatrutide and CagriSema reached 25.0% and 20.4% in phase 3 but are not approved. Research peptides sold online, such as MOTS-c, AOD-9604 and BPC-157, have no completed human trial showing weight loss (PubMed and ClinicalTrials.gov, as of 2026-10-16).

Item	Status
US FDA status	Approved for weight management: semaglutide (Wegovy), tirzepatide (Zepbound), liraglutide (Saxenda), orforglipron (Foundayo, not a peptide), setmelanotide (Imcivree, rare genetic obesity only). Retatrutide, CagriSema, survodutide, mazdutide, MOTS-c, AOD-9604: not approved
Compounding	Retatrutide and cagrilintide “cannot be used in compounding under federal law” (FDA); MOTS-c: PCAC voted 7–5 (2 abstentions) on 2026-07-23 to recommend 503A listing, advisory, no FDA rule yet; AOD-9604: PCAC voted 12–0 against in 2024
WADA (2026 List, in force)	GLP-1 drugs not prohibited, monitored (USADA); MOTS-c prohibited (S4.4.1); AOD-9604 prohibited (S2.2.3); drugs still in clinical development fall under S0 (WADA 2026 List)
WADA 2027 List	No change for these drugs: MOTS-c (S4.4.1), AOD-9604 (S2.2.3) and S0 stay prohibited; semaglutide and tirzepatide stay in the monitoring program, in force 2027-01-01 (WADA 2027 List; USADA)
Strongest evidence	Approved label and Human RCTs for GLP-1 drugs; animal studies only for MOTS-c; no weight-loss study for BPC-157 or GHK-Cu (PubMed, searched 2026-10-16)
Next regulatory step	Retatrutide: Lilly plans a US filing in Q1 2027 (Lilly 8-K); CagriSema: filed 2025-12-18, no FDA decision found as of 2026-10-16 (Novo Nordisk); survodutide, mazdutide: no US filing found (searched 2026-10-16)
Human trials	38 RCTs of GLP-1 drugs and co-agonists in a 2026 review; MOTS-c: no registered trial of MOTS-c itself; 1 of the analog CB4211, completed, no results posted (NCT03998514)
Last checked	2026-10-18

Peptides for weight loss at a glance

Drug	Evidence and status	Best result
Tirzepatide (Zepbound)	Approved; Human RCT, n=2,539	SURMOUNT-1: −20.9% (15 mg) vs −3.1% at 72 weeks
Semaglutide (Wegovy)	Approved; Human RCT, n=1,961	STEP 1: −14.9% vs −2.4% at 68 weeks
Oral semaglutide (Wegovy pill)	Approved 2025; Human RCT, n=307	OASIS 4: −13.6% vs −2.2% at 64 weeks
Orforglipron (Foundayo)	Approved 2026; small molecule; Human RCT, n=3,127	ATTAIN-1: −11.2% (36 mg) vs −2.1% at 72 weeks
Liraglutide (Saxenda)	Approved 2014; Human RCT, n=3,731	SCALE: −8.4 kg vs −2.8 kg at 56 weeks
Setmelanotide (Imcivree)	Approved for rare genetic obesity only; open-label phase 3	Clément 2020: 8 of 10 (POMC) lost ≥10%
Retatrutide	Investigational; Human RCT, n=2,339	TRIUMPH-1: −25.0% (12 mg) vs −3.9% at 80 weeks
CagriSema	Investigational, FDA filing 2025; Human RCT, n=3,417	REDEFINE 1: −20.4% vs −3.0% at 68 weeks
Mazdutide	Not approved in US; Human RCT, n=610	GLORY-1: −14.0% (6 mg) vs +0.3% at 48 weeks
Survodutide	Investigational; Human RCT, n=725	SYNCHRONIZE-1: −13.0% (6.0 mg) vs −5.4% at 76 weeks
MOTS-c	Animal only; no registered trial of MOTS-c itself	Lee 2015: prevented diet-induced obesity in mice
AOD-9604	Human phase 2b failed; animal data	FDA 2024: “lack of evidence” of effectiveness
BPC-157, GHK-Cu	No weight-loss study found	None on PubMed (searched 2026-10-16)

Trial results above come from different trials with different populations and lengths; side-by-side numbers are cross-trial comparisons, not head-to-head results.

Tier 1: approved peptide drugs for weight loss

Tirzepatide (Zepbound)

Tirzepatide acts on the receptors for two gut hormones, GLP-1 and GIP, and showed the largest placebo-subtracted weight loss of the drugs on the market in a 2026 review of 38 trials (Annals review 2026). FDA approved it as Zepbound for chronic weight management in 2023; the same molecule is sold as Mounjaro for type 2 diabetes (FDA). In SURMOUNT-1, adults without diabetes lost 15.0%, 19.5% and 20.9% of body weight on the 5, 10 and 15 mg doses over 72 weeks, against 3.1% on placebo [Human RCT, n=2,539] (Jastreboff 2022). In SURMOUNT-5, a head-to-head obesity trial of the two leading drugs, tirzepatide produced 20.2% weight loss against 13.7% for semaglutide [Human RCT, n=751, open-label] (Aronne 2025). Deeper comparisons are on our retatrutide vs tirzepatide vs semaglutide page.

Semaglutide (Wegovy injection and pill)

Semaglutide is a GLP-1 receptor agonist that mimics a gut hormone involved in appetite. Weekly injections were approved as Wegovy in June 2021, and Wegovy tablets followed in December 2025 (Drugs@FDA). In STEP 1, the injection cut body weight by 14.9% against 2.4% on placebo at 68 weeks, and half the treated group lost 15% or more [Human RCT, n=1,961] (Wilding 2021). The daily 25 mg pill produced 13.6% against 2.2% at 64 weeks in OASIS 4 [Human RCT, n=307] (Wharton 2025).

Orforglipron, liraglutide and setmelanotide

Orforglipron is not a peptide but a “small-molecule, nonpeptide oral” GLP-1 drug; adults on the top dose lost 11.2% against 2.1% on placebo over 72 weeks [Human RCT, n=3,127] (Wharton 2025). FDA approved it as Foundayo on April 1, 2026 (FDA); it is compared in detail on orforglipron vs Zepbound. Liraglutide, the older daily GLP-1 injection approved as Saxenda in 2014 (Drugs@FDA), produced 8.4 kg of weight loss against 2.8 kg on placebo over 56 weeks [Human RCT, n=3,731] (Pi-Sunyer 2015). Setmelanotide (Imcivree) is a melanocortin-4 receptor agonist approved for obesity caused by POMC, PCSK1 or LEPR deficiency confirmed by genetic testing, conditions with about 150 reported cases (FDA), and later for obesity due to Bardet-Biedl syndrome (FDA, Bardet-Biedl). In 2026 it also cut BMI by 16.5% against a 3.3% rise on placebo in acquired hypothalamic obesity [Human RCT, n=120] (TRANSCEND 2026).

Tesamorelin: approved, but not for weight loss

Tesamorelin (Egrifta) is an approved growth-hormone-releasing peptide (Drugs@FDA) studied for belly fat in people with HIV, not general weight loss. In its phase 3 trial, deep abdominal fat fell 10.9% against 0.6% on placebo over 6 months, with no change in fat under the skin, and the gain was “rapidly lost” after stopping [Human RCT, n=404] (Falutz 2010). See tesamorelin vs CJC-1295/ipamorelin for fat loss.

Tier 2: investigational peptides with human trials

These drugs have promising phase 3 results but are not approved in the US and cannot be obtained legally in the US outside clinical trials.

• Retatrutide (GIP, GLP-1 and glucagon receptor agonist): in TRIUMPH-1, adults without diabetes lost 25.0% on the 12 mg dose against 3.9% on placebo over 80 weeks [Human RCT, n=2,339] (Jastreboff 2026). Lilly plans to submit it to FDA in the first quarter of 2027 (Lilly 8-K, August 2026). FDA says it “cannot be used in compounding under federal law” (FDA).
• CagriSema (cagrilintide, an amylin analogue, plus semaglutide): 20.4% against 3.0% on placebo at 68 weeks in REDEFINE 1 [Human RCT, n=3,417] (Garvey 2025). Novo Nordisk filed for FDA approval on December 18, 2025 (Novo Nordisk).
• Mazdutide (GLP-1 and glucagon receptor agonist): 14.0% on 6 mg against a 0.3% gain on placebo at 48 weeks in Chinese adults [Human RCT, n=610] (Ji 2025).
• Survodutide (glucagon and GLP-1 receptor agonist): 13.0% on 6.0 mg against 5.4% on placebo at 76 weeks [Human RCT, n=725] (le Roux 2026); see survodutide vs tirzepatide.

A 2026 systematic review of 38 trials found placebo-subtracted losses of 22.1% for retatrutide and 23.9% for amycretin, against 19.0% for tirzepatide, while noting that differences between trials prevented pooling the results (Annals review 2026).

Tier 3: research peptides sold for fat loss

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA. In mice it activated AMPK, an energy sensor, and prevented diet-induced obesity and insulin resistance [Animal] (Lee 2015). USADA notes there are “no completed human clinical trials” (USADA); ClinicalTrials.gov lists no trial of MOTS-c itself, only a completed trial of an analog, CB4211, with no results posted (NCT03998514). On July 23, 2026, FDA’s advisory committee voted 7–5 with 2 abstentions to recommend MOTS-c for the 503A compounding list, as reported by trade press; the vote is advisory and no FDA rule has followed (FDA meeting page). See MOTS-c vs 5-amino-1MQ.

AOD-9604, a fragment of human growth hormone, reduced weight gain in obese mice [Animal] (Heffernan 2001), but its developer announced in 2007 that phase 2b results did “not support the commercial viability” of the drug for obesity, and FDA found “a lack of evidence” of effectiveness (FDA briefing, 2024). FDA’s advisory committee then voted 12–0 against adding it to the compounding list (FDA minutes).

BPC-157 and GHK-Cu are often listed in weight-loss “stacks”, but no human or animal study testing either for weight loss or obesity was found on PubMed (search, 2026-10-16). Their research is about tissue repair and skin.

Safety and regulatory status

Stomach and gut side effects are the main cost of the approved drugs. Across 38 trials, 76.0% of people on GLP-1 drugs reported gastrointestinal adverse events against 40.1% on placebo, and 10.7% stopped because of side effects against 3.4% (Annals review 2026). FDA lists nausea, diarrhea, vomiting, constipation, injection site reactions, hair loss and reflux for Zepbound, and notes that it causes thyroid C-cell tumors in rats, with the human risk unknown; people with a personal or family history of medullary thyroid cancer or MEN 2 should not use it (FDA). Effects can fade after stopping: in the tesamorelin trial, the fat reduction was “rapidly lost” after switching to placebo.

Unapproved products carry a different risk. FDA has warned companies that sold semaglutide, tirzepatide, retatrutide, survodutide or mazdutide “falsely labeled ‘for research purposes’” and sold with dosing instructions, and urges consumers not to buy these products, which “are of unknown quality and may be harmful to their health” (FDA). The are peptides safe? guide covers this in depth.

For athletes, GLP-1 drugs are not prohibited but WADA is monitoring them (USADA); semaglutide and tirzepatide are in the monitoring program for 2027 (USADA 2027 advisory). On the 2026 List in force, S0 bans drugs “under pre-clinical or clinical development” at all times, MOTS-c is prohibited as an AMPK activator under S4.4.1 and AOD-9604 is named as a growth hormone fragment under S2.2.3 (WADA 2026); the 2027 List, in force from 1 January 2027, keeps all three (WADA 2027).

Anyone who suspects a side effect from a weight-loss peptide or any other drug or product can report it to the FDA through MedWatch.

Which has more evidence for which goal?

• Largest weight loss with an approved drug: tirzepatide has the most evidence, including a head-to-head trial win over semaglutide.
• A pill instead of an injection: oral semaglutide and orforglipron both have phase 3 trials and FDA approval.
• Rare genetic obesity: setmelanotide was the first FDA-approved treatment for obesity due to POMC, PCSK1 or LEPR deficiency, backed by open-label phase 3 trials.
• Muscle, energy or “metabolic” claims for research peptides: MOTS-c has mouse data only; AOD-9604 failed in people.

These are statements about evidence, not recommendations; a clinician is the person to decide which treatment, if any, fits.