# Retatrutide

> Evidence tier A — Controlled human trials · Metabolic · reviewed 2026-11-08
> Source page: https://peptidemeta.com/p/retatrutide/

Also known as: LY3437943

## Quick answers

**What is Retatrutide?**

An investigational triple agonist of the GIP, GLP-1, and glucagon receptors developed by Eli Lilly.

**How strong is the evidence for Retatrutide?**

Tier A (controlled human trials) on the peptidemeta evidence scale. Phase 2 RCTs (NEJM 2023, Lancet 2023) and phase 3 RCTs (TRIUMPH-1, NEJM 2026; TRIUMPH-2/-3/-4); not approved by any regulator as of November 2026.

**Is Retatrutide FDA-approved?**

No. Retatrutide is not approved by the FDA for any use. Investigational; Lilly has said it plans to submit a US Biologics License Application in Q1 2027.

**Is Retatrutide banned in sport?**

Yes. Retatrutide is prohibited in sport by the World Anti-Doping Agency under S0 (non-approved substances).

**How does Retatrutide work?**

Retatrutide is a triple incretin receptor agonist that simultaneously activates GIP, GLP-1, and glucagon receptors. GLP-1 and GIP receptor activation reduces appetite and improves insulin secretion, while glucagon receptor agonism increases energy expenditure and hepatic fatty acid oxidation, producing additive weight loss effects.

**What is known about the safety of Retatrutide?**

Gastrointestinal events (nausea, diarrhea, vomiting) were the most common adverse events in phase 2 and phase 3 trials and were dose-related. Not FDA-approved.

## Key facts

- **Evidence tier:** A (Controlled human trials)
- **FDA:** not approved
- **WADA:** prohibited (S0)
- **Peptide:** yes
- **Sequence:** Y[Aib]QGTFTSDYSI[αMeLeu]LDKKAQ[Aib]AFIEYLLEGGPSSGAPPPS[NH2] (39 residues)
- **Formula:** C221H342N46O68
- **Molecular weight:** 4731.3 g/mol
- **Discovered:** 2022 — Discovery and early clinical data published by Eli Lilly as LY3437943 (Coskun et al., Cell Metab 2022).
- **Routes studied:** Subcutaneous

## Overview

An investigational triple agonist of the GIP, GLP-1, and glucagon receptors developed by Eli Lilly. In the phase 3 TRIUMPH-1 trial, adults with obesity lost 17.6-25.0% of body weight over 80 weeks versus 3.9% with placebo.

## Mechanism

Retatrutide is a triple incretin receptor agonist that simultaneously activates GIP, GLP-1, and glucagon receptors. GLP-1 and GIP receptor activation reduces appetite and improves insulin secretion, while glucagon receptor agonism increases energy expenditure and hepatic fatty acid oxidation, producing additive weight loss effects.

## Effects reported in research

_Reported outcomes, not promises; see the evidence tier._

- Significant body weight reduction
- Improved glycemic control
- Reduced appetite and caloric intake
- Favorable lipid profile changes

## Safety & unknowns

Gastrointestinal events (nausea, diarrhea, vomiting) were the most common adverse events in phase 2 and phase 3 trials and were dose-related. Not FDA-approved. Monitor for potential thyroid C-cell signals as with other incretin agonists.

## Studies

- Jastreboff AM, Kaplan LM, Frías JP, et al. (2023). *Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial*. New England Journal of Medicine. Clinical trial. https://pubmed.ncbi.nlm.nih.gov/37366315/
  In this 48-week phase 2 RCT in 338 adults with obesity, mean weight change ranged from -8.7% (1 mg) to -24.2% (12 mg) versus -2.1% with placebo.
- Jastreboff AM, Kaplan LM, Davies MJ, et al. (2026). *Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity*. New England Journal of Medicine. Clinical trial. https://pubmed.ncbi.nlm.nih.gov/42814954/
  In the 80-week phase 3 TRIUMPH-1 RCT in 2339 adults with obesity without diabetes, mean weight change was -17.6% to -25.0% across doses versus -3.9% with placebo; gastrointestinal events were most common.

## Status sources

- [Jastreboff et al., NEJM 2023 (phase 2 RCT)](https://pubmed.ncbi.nlm.nih.gov/37366315/)
- [TRIUMPH-1 phase 3 RCT, NEJM 2026](https://pubmed.ncbi.nlm.nih.gov/42814954/)
- [Eli Lilly press release, 23 Jul 2026 (TRIUMPH-2/-3; BLA plan)](https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional)
- [KEGG DRUG D12430 — retatrutide (sequence, formula, MW)](https://www.kegg.jp/entry/D12430)
- [WADA Prohibited List 2026 (S0)](https://www.wada-ama.org/en/resources/world-anti-doping-code-and-international-standards/prohibited-list)

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Educational reference only — not medical advice. No dosing information is published. Tiers rate the strength of published evidence, not effectiveness or safety.