Retatrutide

Phase 2 Obesity Trial

A 48-week trial in 338 adults with obesity (BMI 30–50) showed dose-dependent weight loss: 8.7% (1 mg), 17.3% (4 mg), 22.8% (8 mg), and 24.2% (12 mg) versus 2.1% with placebo. Gastrointestinal side effects (nausea, diarrhea) were most common during dose escalation.¹

Liver Fat Reduction (MASLD Trial)

In a separate 48-week trial in adults with metabolic dysfunction-associated steatotic liver disease (MASLD), the 12 mg dose produced 86% relative reduction in liver fat measured by MRI. This exceeds reductions seen with GLP-1-only (~30%) or GLP-1/GIP dual agonists (~47%). The mechanism is glucagon-driven: direct triglyceride mobilization and oxidation in the liver.¹

Body Composition

DXA analysis showed approximately 63:37 fat-to-lean mass loss ratio — meaning about 63% of weight lost came from fat, 37% from lean tissue. This was measured in people with type 2 diabetes, where GIP signaling is impaired. The ratio may be more favorable in non-diabetic populations, but that data does not yet exist. Resistance training and protein intake were not controlled in trials — variables that significantly affect lean mass preservation.¹

Heart Rate Signal

Resting heart rate increases of 2–7 bpm were observed across doses — attributed to glucagon receptor activation. This is a distinguishing safety signal compared to compounds without glucagon activity and requires monitoring in cardiovascular risk phenotypes.¹

All published data is Phase 2; Phase 3 trials are ongoing. Body composition data comes only from type 2 diabetes populations where GIP signaling is impaired. The 63:37 fat:lean ratio may improve in non-diabetics, but this remains untested. Heart rate increases require monitoring. The glucagon arm creates a double-edged profile: aggressive fat loss but proportional muscle loss risk without rigorous anabolic support (adequate protein, resistance training, and potentially GH-axis support). Regulatory status remains investigational (not yet FDA-approved); expected approval pending Phase 3 trial completion.

1. Jastreboff AM et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial." N Engl J Med. 2023. PubMed
2. Rosenstock J et al. "Retatrutide Phase 1b: Multiple Ascending Dose Study." Lancet. 2022. PubMed
3. Rosenstock J et al. "Retatrutide Phase 2: Type 2 Diabetes." Lancet. 2023. PubMed
4. Sanyal AJ et al. "Retatrutide MASLD Substudy: Liver Fat Reduction." Nat Med. 2024. PubMed
5. Jastreboff AM et al. "Retatrutide Phase 2: Body Composition (DXA Substudy)." Lancet Diabetes Endocrinol. 2025. DOI

For laboratory research use only.