Metabolic
CAS
2381089-83-2
Molecular Weight
4900
Da
The most advanced peptide in active clinical development covered on PeptideClear. Retatrutide is a triple hormone receptor agonist targeting GLP-1, GIP, and glucagon receptors simultaneously, producing weight loss results that exceed both semaglutide and tirzepatide. Phase 3 TRIUMPH-1 (May 2026) showed 28.3% mean body weight reduction at 80 weeks on the 12mg dose, the largest result ever reported in a Phase 3 obesity trial, and the TRIUMPH-2 (type 2 diabetes) and TRIUMPH-3 (cardiovascular disease) trials reported positive results in July 2026. NDA filing is anticipated in early 2027. Not FDA approved.
Injectable
Intranasal Suitable
No
Emerging / Clinical Trial
This score is going to move.
Retatrutide's RQS updates as new trial data and the NDA timeline land. Get the updates, plus one compound scored like this every week.
Community signal is early but intense given its recency. Retatrutide doesn't yet have the years of anecdotal accumulation that semaglutide or tirzepatide have. Early adopter reports from clinical trial participants and grey market users emphasize weight loss that exceeds GLP-1 class comparators, with appetite suppression described as more complete. Side effect reports mirror the GLP-1 class; nausea, fatigue, and GI disruption during dose escalation. The community is watching Phase 3 trial data closely. r/GLP1Sourcing and related subreddits are the primary signal sources currently.
Retatrutide is a synthetic triple hormone receptor agonist developed by Eli Lilly. It is the first peptide in this catalog to target three receptors at once: GLP-1 (Glucagon-Like Peptide-1), GIP (Glucose-dependent Insulinotropic Polypeptide), and glucagon, which earned it the nickname "triple G" in the research and longevity community. Its core Phase 3 program has now reported, and the pivotal obesity trial produced the largest average weight loss seen in the class so far. It has not yet been compared head-to-head with semaglutide or tirzepatide, and it is not FDA approved.
Retatrutide's triple agonist mechanism works on three complementary pathways simultaneously. GLP-1 receptor activation suppresses appetite, slows gastric emptying, and stimulates insulin secretion. GIP receptor activation enhances insulin release and may improve the tolerability of GLP-1 side effects like nausea. Glucagon receptor activation increases energy expenditure and promotes fat breakdown in the liver, a mechanism not present in semaglutide or tirzepatide and thought to be responsible for Retatrutide's superior weight loss outcomes in early trials. The combination of appetite suppression, improved insulin dynamics, and increased energy expenditure creates a uniquely potent metabolic effect.
Retatrutide is being investigated primarily for obesity and type 2 diabetes. The pivotal Phase 3 trial, TRIUMPH-1 (n=2,339, 80 weeks), was published in the New England Journal of Medicine in September 2026. Counting everyone who was randomized, the highest dose produced an average weight loss of 25.0%, versus 3.9% on placebo. Lilly's earlier topline estimate, which assumes everyone took the drug as intended, was 28.3%, with 45.3% of participants losing at least 30% of body weight, a level long associated with bariatric surgery. The same trial showed significant reductions in knee osteoarthritis pain and in sleep apnea events. Weight loss was smaller in people with type 2 diabetes (TRIUMPH-2, published in The Lancet) and in people with established heart disease (TRIUMPH-3). TRIUMPH-3 did not show a statistically significant effect on cardiovascular events and was not designed to. Retatrutide is also being studied in metabolic liver disease (MASH, formerly NASH). Phase 2 data published in the NEJM in 2023 had shown roughly 24% weight loss over 48 weeks.
Retatrutide is not FDA approved, so its full risk profile has not been reviewed by regulators. In Phase 3, the most common side effects were gastrointestinal and dose-related. At the highest dose, roughly 4 in 10 participants reported nausea and about 1 in 4 reported vomiting, with diarrhea and constipation also common, particularly during dose escalation. Phase 3 also identified a signal not typical of the GLP-1 class: dysesthesia, an abnormal skin sensation such as burning or tingling, reported by about 12.5% of participants at the highest dose versus 0.9% on placebo. Most cases were mild to moderate. Symptoms of low blood pressure were dose-dependent and more common in people already taking blood pressure medication. About 11% of participants at the highest dose stopped treatment because of side effects, versus about 5% on placebo. Clinical trials excluded people with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, consistent with other GLP-1 based therapies. Not recommended during pregnancy. A meaningful share of weight lost on drugs in this class is lean mass, and muscle preservation remains an active area of investigation. Products sold online as retatrutide are not the drug used in clinical trials, and their contents are unverified.
Injectable (subcutaneous, weekly) in clinical trial settings only. Not commercially available. Compounded versions are beginning to appear through research chemical vendors but without any regulatory oversight or quality assurance, PeptideClear strongly cautions against use of unverified compounded Retatrutide given the absence of established safety data even in approved clinical contexts.
The core Phase 3 program has now reported. TRIUMPH-4 (December 2025) and TRIUMPH-1 (May 2026) were followed in July 2026 by positive results from TRIUMPH-2 in type 2 diabetes and TRIUMPH-3 in established cardiovascular disease. In September 2026, TRIUMPH-1 was published in full in the New England Journal of Medicine and TRIUMPH-2 in The Lancet. A head-to-head trial against tirzepatide (TRIUMPH-5) is expected to complete around the end of 2026. Lilly plans to submit retatrutide for FDA approval in the first quarter of 2027. Retatrutide is not FDA approved, and no legal compounding pathway exists. Before approval, the only legitimate access is through clinical trials or a limited expanded-access program Lilly confirmed in August 2026, available to qualifying patients through their health care providers. A live question is whether retatrutide is legally a biologic. A federal court upheld the FDA's finding that it is not a protein but sent back the question of whether it is analogous to one, and a federal appeals court heard arguments on September 24, 2026. The answer matters because biologics cannot be compounded, which would determine whether a compounded version could ever exist the way semaglutide and tirzepatide did during their shortages. PeptideClear tracks this compound closely and will update as the picture evolves.
https://pubmed.ncbi.nlm.nih.gov/37366315/
https://pubmed.ncbi.nlm.nih.gov/35985340/
https://pubmed.ncbi.nlm.nih.gov/37385280/
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