Retatrutide

A first-in-class triple hormone receptor agonist producing the most profound metabolic effects seen in obesity research to date.

01Overview

Retatrutide (LY3437943) is an investigational triple agonist developed by Eli Lilly that simultaneously activates the GLP-1, GIP, and glucagon receptors. Because it engages one more pathway than tirzepatide and two more than semaglutide, it is often nicknamed a “triple-G” compound.

In the Phase III TRIUMPH program (2026), the highest dose produced roughly 28–30% body-weight reduction over 80–104 weeks, alongside large improvements in glycemic control and reductions in sleep-apnea severity in companion cohorts.

02Mechanism

• GLP-1 activation drives appetite suppression and delayed gastric emptying.
• GIP activation contributes to improved insulin sensitivity and nutrient handling.
• Glucagon activation raises energy expenditure and promotes hepatic fat oxidation — the pathway that distinguishes it from dual agonists.

03Research uses

• Metabolic and obesity research
• Glycemic-control models
• Hepatic-steatosis and energy-expenditure studies

04Key findings

• TRIUMPH-1 reported ~28.3% weight loss at 80 weeks on the 12 mg arm, extending to ~30% at 104 weeks.
• Adverse events in trials were predominantly gastrointestinal and dose-related (nausea, diarrhea, vomiting).
• Eli Lilly has signaled an NDA submission timeline with realistic approval no earlier than late 2027.

05Handling & reconstitution

• Supplied lyophilized; should appear as a uniform white to off-white powder.
• Reconstitute with bacteriostatic water; swirl gently — never shake, as agitation can shear the peptide.
• A correctly reconstituted solution is clear and colorless with no particulates. Store lyophilized cold and protect from light.