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Retatrutide (LY3437943) is an investigational, once-weekly triple hormone receptor agonist being developed by Eli Lilly. Unlike medicines that target only one or two metabolic hormone pathways, retatrutide is designed to activate three receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors.
The compound is being studied for its potential applications in obesity and several obesity-related conditions. Clinical research has evaluated its effects on body weight, glycemic control, cardiovascular and metabolic health, knee osteoarthritis pain, obstructive sleep apnea and other related conditions.
Key Research Features
- Investigational triple hormone receptor agonist
- Also known as LY3437943
- Activates GIP, GLP-1 and glucagon receptors
- Studied as a once-weekly subcutaneous treatment in clinical trials
- Currently undergoing Phase 3 clinical development
- Investigated for obesity and overweight-related conditions
- Also being evaluated in type 2 diabetes and other obesity-related complications
Clinical Research
Earlier Phase 2 research involving adults with obesity found substantial body-weight reductions after 48 weeks of treatment. In the 12 mg group, the mean reduction in body weight was 24.2%, compared with 2.1% with placebo. Gastrointestinal adverse events were among the most common reported effects and were generally dose-related.
More recent Phase 3 results announced by Lilly have also reported substantial weight reduction. In the TRIUMPH-1 trial, participants receiving 12 mg retatrutide achieved an average 28.3% reduction in body weight at 80 weeks. Lilly reported additional positive Phase 3 results in 2026 for populations with obesity or overweight and type 2 diabetes, as well as severe obesity with established cardiovascular disease.
Mechanism of Action
Retatrutide is designed to simultaneously activate three hormone receptors involved in metabolic regulation:
GIP receptor: Associated with nutrient and glucose-related signaling.
GLP-1 receptor: Involved in appetite regulation, glucose control and gastrointestinal signaling.
Glucagon receptor: Involved in energy metabolism and regulation of glucose and lipid metabolism.
By combining these three pathways within a single molecule, retatrutide is being investigated as a potential next-generation approach to metabolic and weight-management therapy.
Current Development Status
Retatrutide remains an investigational medication. As of August 2026, it has not been approved by the FDA or any other regulatory agency for routine public use. Lilly is continuing its Phase 3 clinical development program and has stated that it plans to submit a Biologics License Application to the FDA in Q1 2027.
