At a glance
- Mechanism of action
- Triple agonist (GLP-1, GIP and glucagon): builds on the appetite and insulin effects of GLP-1/GIP and adds glucagon, which raises energy expenditure in the liver and actively burns fat.
- Benefits & use
- In Phase 3 (TRIUMPH-4, 12 mg) up to 28.7 % weight loss at 68 weeks - the largest reduction ever reported in a randomized Phase 3 trial of a GLP-1-class compound. TRIUMPH-1 (80 weeks) confirmed 28.3 %, with 45.3 % of participants achieving ≥30 % loss. In type 2 diabetes (TRANSCEND-T2D-1) an additional -16.8 % weight plus -1.7 to -2.0 % HbA1c. Key secondary endpoints: 75.8 % reduction in knee pain in obesity with osteoarthritis, ~20 % LDL reduction, 72 % prediabetes remission.
- Study status
- Level 3: Phase 3 (TRIUMPH) largely complete - TRIUMPH-4 (12/2025) and TRIUMPH-1 (05/2026) positive; TRANSCEND-T2D-1 (03/2026) positive. NDA filing expected Q4 2026, FDA/EMA approval earliest 2027.
- Dosing note
- Experimental, vials 5-60 mg; no approved dosing schemes yet. No dosing instructions - information only.
Use in the injection calculator
Retatrutide is a triple agonist (GLP-1, GIP and glucagon) and the third generation after semaglutide and tirzepatide. In Phase 2 it achieved up to 24.2 % weight loss in 48 weeks. Evidence level 3.
How does retatrutide work?
Retatrutide uses the foundation of GLP-1 and GIP (appetite, insulin) and adds glucagon: glucagon raises energy expenditure in the liver, so the body burns more calories even at rest and actively breaks down stored fat. This third pathway is what sets retatrutide apart from earlier weight-loss drugs and drives its unusually strong results.
What is the special benefit?
The triple attack shows unusually strong efficacy. Notably, in trials fatty liver (steatosis) improved substantially in nearly all participants - relevant for NASH. Compared with tirzepatide, the added glucagon action targets liver fat more directly, which makes retatrutide especially interesting for metabolic disease beyond weight alone.
What does Phase 3 mean?
Phase 3 (the TRIUMPH trials) tests the compound in many thousands of people over 1-2 years as the final proof of efficacy and safety before approval. If results stay positive, FDA/EMA approval is expected around 2026-2027. Because dosing is still experimental, see the FAQ before estimating volumes, and use the injection calculator only for educational reconstitution maths.
Note: Educational information, not medical advice. Many of these substances are experimental and not approved for human use.
Related peptides
Sources
- Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs - TRIUMPH-4 topline (Investor Relations)
- Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight - TRANSCEND-T2D-1 topline (Investor Relations)
- Retatrutide (LY3437943) - Phase 2 NEJM 2023