Retatrutide
LY3437943 — GLP-1/GIP/Glucagon Triple Agonist
What is Retatrutide?
Retatrutide is a triple receptor agonist developed by Eli Lilly targeting GLP-1, GIP, and glucagon receptors simultaneously. It is the first triple agonist to demonstrate weight loss results exceeding dual agonists like Tirzepatide, with Phase 2 data showing approximately 24.2% body weight reduction at 48 weeks — the largest reported in a pharmaceutical trial at that time.
By adding glucagon receptor agonism to the GLP-1/GIP dual mechanism, Retatrutide adds thermogenesis — increased energy expenditure — on top of appetite suppression and insulin sensitization. The glucagon component drives brown adipose tissue activation and hepatic fat clearance, producing a broader metabolic effect profile than any previous GLP-1 class drug.
Research Evidence
Phase 2 trial in NEJM (2023) demonstrated approximately 24.2% mean body weight reduction at 48 weeks at the highest dose (12mg) — the largest weight loss reported in a pharmaceutical trial at that time.
Significant reductions in visceral adipose tissue and liver fat, consistent with the glucagon receptor component driving hepatic fat clearance beyond what GLP-1/GIP agonists achieve.
Phase 3 TRIUMPH trials ongoing as of 2026. Full efficacy and safety data not yet published. Regulatory approval anticipated 2026-2027.
Evidence grades: Gold = RCT human data · Silver = consistent animal/human data · Bronze = limited or preliminary
Dosing Protocols
Reconstitution Guide
This compound does not require reconstitution — it is available as a pre-mixed injectable or oral formulation.
Frequently Asked Questions
How does Retatrutide compare to Tirzepatide?
Retatrutide hits 3 receptors (GLP-1, GIP, glucagon) vs Tirzepatide's 2 (GLP-1, GIP). Phase 2 data shows approximately 24.2% body weight reduction vs Tirzepatide's 20.9% in SURMOUNT-1. The glucagon component adds thermogenesis — increased calorie burning — which is absent in Tirzepatide.
When will Retatrutide be available?
Phase 3 TRIUMPH trials are ongoing as of 2026. Regulatory submission to FDA is anticipated following trial completion, with potential approval in 2026-2027. It will require a prescription and will not be available through compounding pharmacies as a novel patented drug.
References
- [1]Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity — a Phase 2 trial. N Engl J Med. 2023;389(6):514-526.
- [2]Eli Lilly and Company. A Study of Retatrutide (LY3437943) in Participants With Obesity (TRIUMPH-1). ClinicalTrials.gov NCT05584826.
This profile was prepared using AI-assisted research synthesis. Citations are provided where applicable — verify with primary sources before clinical application.
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