Retatrutide
Also known as Reta, LY3437943, LY-3437943, Triple G
Retatrutide (LY3437943) is an investigational once-weekly injectable triple agonist of the GIP, GLP-1, and glucagon receptors studied for obesity and metabolic disease, producing the largest weight reductions reported among incretin-class agents in Phase 2 trials.
Typical use cases
Dosing guidelines
Titration
In published trials the dose was escalated gradually (e.g., starting around 1-2 mg weekly and stepping up roughly every 4 weeks toward target doses of 4, 8, or 12 mg), an approach commonly described as helping minimize gastrointestinal effects during escalation.
Reconstitution
Research-grade lyophilized powder is typically reconstituted with bacteriostatic water; the volume is chosen to give a convenient concentration for the intended dose. Swirl gently rather than shaking; do not use if cloudy or discolored.
Injection sites
Subcutaneous injection, typically rotated among the abdomen, thigh, and upper arm.
Storage & handling
Lyophilized powder is commonly stored refrigerated (2-8 C) and protected from light; after reconstitution it is kept refrigerated and used within a limited window. Avoid freezing reconstituted solution.
Side effects
- Nausea
- Vomiting
- Diarrhea
- Constipation
- Increased heart rate (dose-dependent)
- Gallbladder events (e.g., cholecystitis)
Research summary
Retatrutide is a 39-amino-acid lipidated synthetic peptide developed by Eli Lilly that simultaneously activates the GIP, GLP-1, and glucagon receptors, the latter adding an energy-expenditure component on top of the appetite and glycemic effects of dual incretin agonists. Human evidence comes primarily from a published Phase 2 program: a 48-week obesity trial (NEJM 2023, n=338) reported dose-dependent least-squares mean weight reductions up to about 24% at the 12 mg dose, a Phase 2 type 2 diabetes trial (Lancet 2023, n=281) showed HbA1c reductions of roughly 1.3-2.0 percentage points with weight loss up to ~17% at 12 mg, and a Phase 2a MASLD trial (Nature Medicine 2024, n=98) reported large reductions in liver fat (about 80% relative reduction at the 8-12 mg doses). Reported benefits also include improvements in blood pressure, triglycerides, and waist circumference. The dominant adverse events are gastrointestinal (nausea, vomiting, diarrhea, constipation), generally mild-to-moderate and concentrated during dose escalation, with dose-dependent heart-rate increases and isolated gallbladder events noted. Important limitations: retatrutide remains investigational and is not approved by any regulator, long-term cardiovascular outcome and safety data are not yet published, and the Phase 2 trials were of modest size and limited duration while the larger Phase 3 TRIUMPH program is still maturing. This entry is educational only and not medical advice.
Key references
- https://en.wikipedia.org/wiki/Retatrutide
- https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
- https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01053-X/abstract
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11271400/
- https://pubchem.ncbi.nlm.nih.gov/compound/171390338
- https://investor.lilly.com/news-releases/news-release-details/lillys-phase-2-retatrutide-results-published-new-england-journal
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