Retatrutide
GLP-3 or Triple G
Metabolic
CAS
2381089-83-2
Molecular Weight
4900
Da
Human RCT
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 III TRIUMPH-1 results (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. NDA filing anticipated late 2026 to early 2027. Not FDA approved.
Injectable
Intranasal Suitable
No
Emerging / Clinical Trial
Community Signal
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.
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What It Is
Retatrutide is a synthetic triple hormone receptor agonist developed by Eli Lilly, currently in Phase III clinical trials. It is the first peptide in this catalog to simultaneously target three receptors, GLP-1 (Glucagon-Like Peptide-1), GIP (Glucose-dependent Insulinotropic Polypeptide), and glucagon receptors, earning it the nickname "triple G" in the research and longevity community. Early clinical trial data has shown weight loss results that exceed those of semaglutide and tirzepatide, positioning Retatrutide as potentially the most powerful metabolic peptide in clinical development. It is not yet FDA approved.
Mechanism of Action
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.
Use Cases
Retatrutide is being investigated primarily for obesity and type 2 diabetes management. Phase III TRIUMPH-1 data (May 2026, n=2,339) showed mean body weight reduction of 28.3% at 80 weeks on the 12mg dose, with 45.3% of participants achieving at least 30% weight loss, a threshold previously associated only with bariatric surgery. In a 104-week extension subgroup, average reduction reached 30.3%. Phase 2 data published in the New England Journal of Medicine in 2023 had shown approximately 24% weight loss over 48 weeks.It is also being studied for non-alcoholic steatohepatitis (NASH), cardiovascular risk reduction, and metabolic syndrome. The longevity and biohacking community has taken significant interest in Retatrutide ahead of its anticipated FDA approval.
Known Risks
As Retatrutide has not yet received FDA approval its full risk profile is not yet established. Side effects observed in Phase II trials mirror those of other GLP-1 based therapies — primarily gastrointestinal including nausea, vomiting, diarrhea, and constipation during dose escalation. The addition of glucagon receptor agonism introduces theoretical considerations around liver function and glucose regulation that are being monitored in ongoing trials. Contraindicated in individuals with 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. Muscle mass preservation during weight loss is an active area of investigation. Not approved for human use outside of clinical trial settings.
Available Forms
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.
Regulatory Status
Phase III TRIUMPH-1 and TRIUMPH-4 trials have reported positive results. TRIUMPH-2 (T2D), TRIUMPH-3 (cardiovascular disease), and additional readouts are expected through late 2026. NDA filing is anticipated in the late 2026 to early 2027 window. Not FDA approved. No compounding pathway exists. PeptideClear will update this profile as the regulatory status evolves, this is one of the most actively tracked peptides on the platform given its proximity to potential approval.
Sources
https://pubmed.ncbi.nlm.nih.gov/37366315/
https://pubmed.ncbi.nlm.nih.gov/35985340/
https://pubmed.ncbi.nlm.nih.gov/37385280/
Similar Compounds
GLP-1, Semaglutide, Tirzepatide, MK-677
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