Retatrutide

Retatrutide is an experimental "triple agonist" peptide that activates three hormone receptors at once: GLP-1, GIP, and glucagon. Early clinical trials show it may be the most powerful weight loss medication ever developed. **Why three receptors?** Each receptor contributes something different: • **GLP-1:** Reduces appetite and improves blood sugar control • **GIP:** Enhances insulin response and may boost the effects of GLP-1 • **Glucagon:** Increases energy expenditure and burns liver fat Together, this mimics what happens after weight loss surgery — but without surgery. **What the research shows:** • Phase 2 trials showed up to 24% body weight loss — unprecedented for any medication • Significant improvements in blood sugar and metabolic health • Particularly effective at reducing liver fat (important for fatty liver disease) • Currently in Phase 3 trials for obesity and type 2 diabetes **How it compares:** • Semaglutide (Wegovy): ~15-17% weight loss • Tirzepatide (Zepbound): ~20-22% weight loss • Retatrutide: ~24% weight loss in trials **Important to know:** Retatrutide is not yet FDA-approved and is still in clinical development. Results from larger Phase 3 trials are pending. --- **Sources:** Jastreboff AM, et al. (2023) New England Journal of Medicine | Targher G, et al. (2025) Clinical and Molecular Hepatology. DOI:10.3350/cmh.2025.0744

Phase 3 results are recent top-line announcements not yet fully peer-reviewed; GI tolerability and dropout rates are significant concerns; not approved by any regulator; long-term safety and outcomes data pending.

Once-weekly subcutaneous injection; engineered balanced agonist of GLP-1, GIP, and glucagon receptors, combining appetite suppression, insulinotropic action, and energy expenditure. Long half-life supports weekly dosing (clinicaltrials.gov program under review).