Retatrutide
Also known as: LY-3437943
An investigational triple-agonist peptide from Eli Lilly that targets GLP-1, GIP, and glucagon receptors at the same time. In clinical trials, it has produced the highest weight loss numbers ever recorded for an obesity drug.
How it works
Retatrutide activates three receptors at once: GLP-1, GIP, and glucagon. GLP-1 and GIP work together to reduce appetite and improve blood sugar control, while glucagon receptor activation boosts energy expenditure and fat burning. This triple action is what sets it apart from dual agonists like tirzepatide.
Common uses
- Obesity and weight management (clinical trials)
- Type 2 diabetes (clinical trials)
- Metabolic dysfunction-associated steatotic liver disease (MASH)
- Obstructive sleep apnea related to obesity
- Knee osteoarthritis related to obesity
Side effects
- Nausea (up to 60% at highest dose, mostly during dose escalation)
- Diarrhea (about 33% at higher doses)
- Vomiting
- Constipation
- Decreased appetite
- Dysesthesia (tingling or altered skin sensations, 9-21% depending on dose)
- Rare: pancreatitis
Key research
- Phase 2 trial (NEJM 2023) showed 24.2% average weight loss at 48 weeks with 12 mg dose
- TRIUMPH-4 Phase 3 trial reported 28.7% mean weight loss (71.2 lbs average) at 68 weeks, the highest ever in an obesity trial
- TRIUMPH program includes 8 Phase 3 trials across obesity, diabetes, MASH, sleep apnea, and more
Safety notes
- Not yet FDA-approved. Still in Phase 3 clinical trials as of early 2026
- NDA filing expected late 2026 or early 2027
- Carries the same thyroid C-cell tumor warning seen with other GLP-1 drugs (based on rodent studies)
- Not available outside of clinical trials or research settings
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