A 40-week, phase 3, double-blind, placebo-controlled RCT evaluated retatrutide (4 mg, 9 mg, or 12 mg once-weekly subcutaneous injection) as monotherapy vs. placebo in 537 adults with type 2 diabetes inadequately controlled by diet and exercise alone (HbA1c 7.0–9.5%, BMI ≥23 kg/m²).
All retatrutide doses significantly reduced HbA1c vs. placebo at 40 weeks (treatment differences: −0.88% at 4 mg, −1.04% at 9 mg, −1.12% at 12 mg; all p<0.0001). Body weight fell by 11.5%, 13.9%, and 15.3% with 4 mg, 9 mg, and 12 mg, respectively, vs. −2.6% with placebo. No severe hypoglycaemia was reported; GI adverse events were mild-to-moderate and self-limited.
- Short 40-week duration limits conclusions about long-term durability, cardiovascular outcomes, and safety. - Diet-and-exercise-only population means results may not generalise to those on background antidiabetic agents. - Funded by Eli Lilly, introducing potential industry bias.
Retatrutide as monotherapy produced clinically meaningful HbA1c reductions and ~12–15% body weight loss in type 2 diabetes patients not controlled by lifestyle alone, with no severe hypoglycaemia — making it a potentially strong option for patients who need both glycaemic and weight management. Clinicians should counsel patients on expected mild-to-moderate GI side effects, especially early in treatment.
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