Retatrutide is an investigational, once-weekly injectable medication developed by Eli Lilly that targets three hormone receptors—GLP-1, GIP, and glucagon—to manage obesity and type 2 diabetes. Phase 2 trials showed significant results, with participants losing up to 24% of their body weight in 48 weeks, with Phase 3 trials concluding in 2026 and potential FDA approval expected in late 2026 or 2027.
Key Findings on Retatrutide
- Mechanism of Action: Known as a “triple agonist,” it acts on GLP-1, GIP, and glucagon receptors. While GLP-1 and GIP manage appetite and insulin, the addition of glucagon increases energy expenditure, leading to higher calorie burning.
- Weight Loss Efficacy: Phase 2 studies indicated that retatrutide can lead to substantial weight reduction, with higher doses (8-12 mg) yielding roughly 24% weight loss, which is highly competitive with bariatric surgery results.
- Other Benefits: Trials show improvements in liver fat (significant reduction in fatty liver), blood pressure, and lipid metabolism.
- Side Effects: The most common adverse effects are gastrointestinal (nausea, diarrhea, vomiting, constipation), which are typically mild-to-moderate and related to dosage increases.
- Trial Status: Phase 3 trials (TRIUMPH) are ongoing and expected to finish in early-to-mid 2026.
Potential Uses
Beyond general obesity, studies are investigating retatrutide for:
- Obesity with type 2 diabetes.
- Obesity-related obstructive sleep apnea (OSA).
- Knee osteoarthritis (OA) related to weight.
