Independent research intelligence on retatrutide (LY3437943) — the first molecule to simultaneously activate GLP-1, GIP, and glucagon receptors. Not yet approved. Tracking the science for Nigeria.
Retatrutide (LY3437943) is an investigational triple hormone receptor agonist developed by Eli Lilly and Company. It is the first molecule designed to simultaneously activate three metabolic receptors — an approach that targets multiple pathways involved in weight regulation and metabolic health.
Glucagon-Like Peptide-1
Reduces appetite and food intake by signaling satiety to the brain. Slows gastric emptying. The same target used by semaglutide-based therapies.
APPETITE REGULATIONGlucose-Dependent Insulinotropic Polypeptide
Enhances insulin sensitivity and improves fat metabolism. Works synergistically with GLP-1 to amplify metabolic benefits. Also targeted by tirzepatide.
FAT METABOLISMGlucagon Receptor
Increases energy expenditure and promotes fat burning. This is the novel addition that sets retatrutide apart. No other approved medication targets this receptor for weight management.
ENERGY EXPENDITURESingle-agonist therapies (GLP-1 only) primarily reduce appetite. Dual-agonist therapies (GLP-1 + GIP) add improved fat metabolism. Retatrutide's triple-agonist approach adds increased energy expenditure through the glucagon receptor — addressing weight from three simultaneous angles. Published Phase 2 data in the New England Journal of Medicine showed this approach produced meaningful weight reduction in study participants.
REF: Jastreboff et al., NEJM 2023; 389:514-526
Retatrutide is progressing through Eli Lilly's TRIUMPH clinical trial program. Documented path to potential approval and availability.
Safety and dosing parameters established in initial human trials.
Results published in the New England Journal of Medicine. Demonstrated meaningful weight reduction.
Eight Phase 3 trials underway. TRIUMPH-4 reported positive topline results in December 2025.
TRIUMPH-4: PRIMARY ENDPOINT MET
Seven additional trials read out through 2026.
Expected regulatory submission based on TRIUMPH program data.
Projected timeline for regulatory approval. Subject to change.
Dependent on global rollout and NAFDAC regulatory pathway.
How does retatrutide compare to existing GLP-1 therapies? Factual overview for educational purposes only.
| Parameter | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Mechanism | GLP-1 agonist | GLP-1 + GIP agonist | GLP-1 + GIP + Glucagon |
| Receptors | 1 | 2 | 3 |
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
| FDA Status | APPROVED | APPROVED | PHASE 3 |
| Dosing | Once weekly | Once weekly | Once weekly |
| Brand Names | Ozempic®, Wegovy® | Mounjaro®, Zepbound® | Not yet branded |
| Unique Aspect | Most clinical data and longest track record | Dual receptor synergy | First to add glucagon for energy expenditure |
This comparison is for educational purposes only. Ozempic® and Wegovy® are registered trademarks of Novo Nordisk A/S. Mounjaro® and Zepbound® are registered trademarks of Eli Lilly and Company. Retatrutide is an investigational compound and is not approved for any use.
Published findings from leading medical journals and clinical trial registries.
Phase 2 randomised, double-blind, placebo-controlled trial evaluating retatrutide in adults with obesity. Published in the New England Journal of Medicine.
Jastreboff et al., NEJM 2023; 389:514-526
First randomized trial of the triple GLP-1/GIP/glucagon receptor agonist. Demonstrated dose-dependent weight reduction over 48 weeks in adults with BMI 30+ or BMI 27+ with comorbidities.
First successful Phase 3 trial results. Evaluated retatrutide in adults with obesity or overweight and knee osteoarthritis. Met primary and key secondary endpoints.
Eli Lilly Investor Relations, Dec 11, 2025
First Phase 3 readout from the eight-trial TRIUMPH program. Positive topline results in obesity with knee OA. Full data expected at a future medical congress.
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