Peptides
Retatrutide
GIP/GLP-1/Glucagon Triple Receptor Agonist
Category
Triple agonist (GLP-3)
Half-life
~6 days
Typical dose
1mg → 12mg (escalating)
Frequency
Once weekly
Route
Subcutaneous injection
Mechanism
Retatrutide activates three hormone receptors simultaneously: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. GLP-1 and GIP suppress appetite and slow gastric emptying. The glucagon receptor drives the liver to oxidize stored fat, elevating ketone bodies 2–3× and creating a metabolic state favoring fat loss over dietary fuel. This triple mechanism produces greater weight loss than dual agonists and uniquely clears hepatic fat.
Research summary
Phase 2b (NCT04881383): 24% weight loss at 48 weeks. Phase 3: 25% mean weight loss at 80 weeks in 2,339 patients — no plateau observed at 2 years. NAFLD sub-study: 86% liver fat clearance, 93% of patients normalized. Two-thirds of patients on highest dose reclassified out of obesity (BMI below 30). FDA filing expected late 2026.
Storage
Lyophilized: −20°C. Reconstituted: 2–8°C up to 28 days.
Key studies
Jastreboff AM, et al. (2023). Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. NEJM. DOI: 10.1056/NEJMoa2301972
Frequently asked questions
How much weight loss does retatrutide cause?
Phase 3 trials showed 25% mean body weight reduction at 80 weeks. Patients with BMI over 35 lost approximately 84 pounds — 30% of starting body weight. No weight loss plateau was observed at 2 years.
Is retatrutide FDA approved?
No. Retatrutide is not FDA approved as of 2025. Eli Lilly is expected to file for approval in late 2026, with a decision expected in late 2027.
How does retatrutide differ from tirzepatide?
Tirzepatide targets GIP and GLP-1 receptors (dual agonist). Retatrutide adds glucagon receptor activation as a third mechanism, producing greater weight loss, metabolic fat burning, and unique fatty liver clearance not seen with tirzepatide.
Does retatrutide treat fatty liver?
In a Phase 2 NAFLD sub-study, retatrutide cleared 86% of liver fat. 93% of patients reached normal liver fat levels. No currently approved drug achieves this outcome for NAFLD.
For research use only. Not intended for human consumption. Not medical advice. Consult a licensed physician before use.