Peptide Profile
GLP-3 RTA
GIP, GLP-1, and glucagon receptor triple agonist
CLINICAL DEVELOPMENT STAGE:
Phase 3
GLP-3 RTA is a research compound corresponding to retatrutide, an investigational triple receptor agonist that targets the GIP, GLP-1, and glucagon receptor pathways. Retatrutide is being investigated clinically for its effects on metabolic regulation, body weight, and related cardiometabolic outcomes.
Compound Overview
Molecular Formula
C₂₂₁H₃₄₂N₄₆O₆₈
Molecular Weight
4731.33 g/mol
CAS Number
2381089-83-2
Classification
GIP, GLP-1, and glucagon receptor triple agonist
Regulatory Status
INVESTIGATIONAL · NOT FDA APPROVED
Targets / Receptors
GIP receptor (GIPR); GLP-1 receptor (GLP-1R); glucagon receptor (GCGR)
Research Focus
Obesity and body-weight regulation; type 2 diabetes and glycemic control; cardiovascular and renal outcomes; metabolic dysfunction-associated steatotic liver disease (MASLD); obstructive sleep apnea; and obesity-associated musculoskeletal conditions.
Mechanism of Action
GLP-3 RTA corresponds to retatrutide, an investigational peptide engineered to activate three metabolically relevant receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor, glucagon-like peptide-1 (GLP-1) receptor, and glucagon receptor.
Retatrutide’s activity at the GIP and GLP-1 receptors is associated with pathways involved in glucose-dependent insulin secretion, appetite regulation, and energy intake. Its additional glucagon receptor activity distinguishes it from single- and dual-receptor incretin agonists and is being investigated for its potential effects on energy expenditure and metabolic regulation.
The compound’s biological activity reflects the combined effects of these three receptor pathways rather than the action of any single receptor in isolation. The relative contribution of each receptor pathway to observed clinical outcomes remains an active area of investigation.
Research Evidence
Retatrutide has been evaluated across Phase 2 and Phase 3 clinical trials investigating obesity, type 2 diabetes, and related cardiometabolic conditions.
In a randomized Phase 2 trial involving 338 adults with obesity or overweight plus a weight-related condition, retatrutide produced dose-dependent reductions in body weight over 48 weeks. Participants receiving the 12 mg dose had a mean body-weight reduction of 24.2% at week 48, compared with 2.1% with placebo.
More recent Phase 3 results have expanded the evidence base. In TRIUMPH-1, participants receiving 12 mg retatrutide lost an average of 28.3% of body weight at 80 weeks. In TRIUMPH-2, adults with obesity or overweight and type 2 diabetes receiving 12 mg lost an average of 20.8% at 80 weeks, with A1C reductions of up to 1.6 percentage points. Results have also been reported from additional Phase 3 studies evaluating retatrutide across obesity and related cardiometabolic conditions.
Retatrutide remains investigational and is not approved by any regulatory agency. Additional Phase 3 studies are ongoing across obesity, type 2 diabetes, cardiovascular and renal outcomes, metabolic dysfunction-associated steatotic liver disease (MASLD), and other obesity-related conditions.
Safety & Limitations
Retatrutide remains investigational, and its safety and efficacy continue to be evaluated in clinical trials.
In the Phase 2 obesity trial, the most commonly reported adverse events were gastrointestinal and were generally mild to moderate in severity. Gastrointestinal events were dose-related and were partially mitigated by use of a lower starting dose. Dose-dependent increases in heart rate were also observed, peaking at 24 weeks and declining thereafter.
Results from clinical trials should not be interpreted as establishing safety or efficacy for uses that have not received regulatory approval. Retatrutide has not been approved by any regulatory agency and is not currently available for public use.
Key References
Jastreboff AM, Kaplan LM, Frías JP, et al.
Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
New England Journal of Medicine. 2023;389:514–526.
Eli Lilly and Company.
What to Know About Retatrutide
Updated July 2026.
Eli Lilly and Company.
TRIUMPH-1 Phase 3 Results
May 21, 2026.
Eli Lilly and Company.
TRIUMPH-2 and TRIUMPH-3 Phase 3 Results
July 23, 2026.
Last scientifically reviewed: 09/08/2026