In-depth entry

Retatrutide

also known as: LY3437943, Triple-G

An investigational triple hormone agonist that produced ~24% weight loss at 48 weeks in Phase 2 — the largest in any single-agent obesity trial to date.

A synthetic peptide agonist at GLP-1, GIP, and glucagon receptors, with glucagon agonism adding an energy-expenditure component on top of appetite suppression.

Mechanism of action

Triple agonism at GLP-1, GIP, and glucagon receptors. GLP-1 and GIP contribute insulin-sensitization and appetite suppression; glucagon agonism adds thermogenic effects and increased energy expenditure, producing a compound effect on weight loss. The glucagon component requires careful dose titration to avoid hyperglycemia.

Primary uses

Obesity (Phase 3)
Type 2 diabetes (Phase 3)
MASH / liver disease (Phase 2)

Typical dosing

1–12 mg weekly (subcutaneous)

Dose-ranging ongoing; Phase 2 used 1/4/8/12 mg weekly doses with 8 and 12 mg producing maximum weight loss.

Regulatory status

Investigational. In Phase 3 trials (TRIUMPH program) for obesity and type 2 diabetes. Developed by Eli Lilly. Expected regulatory submission 2026–2027.

References

[clinical-trial] Jastreboff AM, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." N Engl J Med, 2023;389:514-526.
[clinical-trial] Rosenstock J, et al. "Retatrutide in Patients with Type 2 Diabetes — A Phase 2 Trial." Lancet, 2023;402:529-544.
[clinical-trial] ClinicalTrials.gov NCT05882045 (TRIUMPH-1, Phase 3 obesity trial).

Related peptides

Tirzepatide

A once-weekly GLP-1/GIP dual agonist that produced unprecedented weight loss in SURMOUNT trials — up to ~21% at highest dose.

Semaglutide

A once-weekly GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

Liraglutide

The first once-daily GLP-1 analog to be FDA-approved for both type 2 diabetes (Victoza) and chronic weight management (Saxenda).

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.