Retatrutide
Reta or Triple G
Metabolic
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 in Phase II trials (~24% body weight) that exceed both semaglutide and tirzepatide. Currently in Phase III trials with Eli Lilly. Not FDA approved or commercially available. PeptideClear is actively tracking its path to potential approval.
Injectable
Emerging / Clinical Trial
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.
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 management. Phase II trial data published in the New England Journal of Medicine in 2023 showed average weight loss of approximately 24% of body weight over 48 weeks — significantly exceeding results seen with semaglutide (~15%) and tirzepatide (~21%). 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.
As Retatrutide is still in clinical trials 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.
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.
Currently in Phase III clinical trials. Not FDA approved. No compounding pathway exists. Eli Lilly has not announced a projected approval timeline publicly though Phase III completion is anticipated in the 2025-2026 timeframe. 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.
https://pubmed.ncbi.nlm.nih.gov/37366315/
https://pubmed.ncbi.nlm.nih.gov/35985340/
https://pubmed.ncbi.nlm.nih.gov/37385280/
GLP-1, Semaglutide, Tirzepatide, MK-677