Retatrutide (LY3437943) is a triple hormone receptor agonist developed by Eli Lilly, simultaneously activating the GIP, GLP-1, and glucagon receptors. Phase 2 trials showed approximately 24% mean body weight reduction at 48 weeks, the largest reported for any obesity drug to date.
Retatrutide is a synthetic peptide developed by Eli Lilly that acts as a single-molecule agonist at three distinct hormone receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. This triple receptor engagement is the key distinction from earlier obesity drugs. GLP-1 agonists like semaglutide activate one receptor; dual agonists like tirzepatide activate two (GIP and GLP-1). Retatrutide adds glucagon receptor agonism, which independently promotes energy expenditure and fatty acid oxidation in the liver. [3]
The compound is not FDA-approved and is not available through any approved pharmaceutical channel. As of 2026, it is in Phase 3 clinical trials for obesity and type 2 diabetes under Eli Lilly's development program. Research-grade retatrutide sold by peptide vendors is not equivalent to the pharmaceutical compound used in those trials.
Retatrutide has the strongest Phase 2 weight loss data of any obesity compound yet published. The 24% mean weight reduction in the NEJM trial is clinically meaningful by any benchmark, and the MASLD findings add a hepatic dimension that positions the compound for a broad cardiometabolic indication. [1] [2] The addition of glucagon receptor agonism is both the compound's distinguishing feature and the element requiring the most careful safety monitoring: sustained glucagon activity can raise blood glucose and heart rate, and the long-term metabolic consequences of triple receptor co-stimulation in humans are still being characterized in the ongoing Phase 3 program.
The obesity drug landscape is moving rapidly. Tirzepatide (dual GIP/GLP-1) was approved in 2022 and 2023, and retatrutide may follow pending Phase 3 outcomes. Researchers following this compound should treat the Phase 2 findings as hypothesis-generating: the sample size, duration, and patient populations in those trials were not designed to detect cardiovascular outcomes, long-term weight maintenance, or safety signals requiring larger exposure. Phase 3 results will be the determining evidence. [3]
| Parameter | Detail |
|---|---|
| Common vial sizes | Varies by vendor; 5 mg and 10 mg most common for research supply |
| Supplied as | Lyophilized powder |
| Administration studied | Once-weekly subcutaneous injection in all published clinical trials [1] |
| Dose range (Phase 2) | 0.5 mg to 12 mg weekly; weight loss was dose-dependent up to 12 mg [1] |
| Half-life | Approximately 6 days in humans (supports once-weekly dosing) |
| Regulatory status | Not FDA-approved; Phase 3 trials ongoing as of 2026 |