Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial.
Level 2 - randomized trial
Substudy of a phase 2 double-blind randomized controlled trial
PubMed 40609566 · doi:10.1016/S2213-8587(25)00092-0
What was done
In a body composition substudy of a phase 2, double-blind, parallel-group, placebo-controlled randomized trial across 42 US medical centers, adults aged 18–75 with type 2 diabetes (HbA1c 7.0–10.5%, BMI 25–50 kg/m²) were evaluated. A total of 189 participants were enrolled across groups receiving once-weekly subcutaneous placebo (n=29), dulaglutide 1.5 mg (n=34), or retatrutide at 0.5 mg (n=32), 4 mg pooled (n=31), 8 mg pooled (n=33), or 12 mg (n=30). The prespecified primary substudy outcome was percent change in total fat mass from baseline to week 36 measured by dual-energy X-ray absorptiometry (DXA).
What was found
Percent reduction from baseline in total fat mass was 4.9% (SE 1.4%) with retatrutide 0.5 mg, 15.2% (SE 3.2%) with retatrutide 4 mg pooled, 26.1% (SE 2.5%) with retatrutide 8 mg pooled, 23.2% (SE 3.0%) with retatrutide 12 mg, 2.6% (SE 1.6%) with dulaglutide, and 4.5% (SE 1.2%) with placebo. Least squares mean difference versus placebo was -0.4% (95% CI -4.0 to 3.2, p=0.83) for 0.5 mg, -10.7% (-17.2 to -4.2, p=0.0013) for 4 mg, -21.6% (-27.1 to -16.1, p<0.0001) for 8 mg, and -18.7% (-25.1 to -12.3, p<0.0001) for 12 mg. Serious adverse events occurred in 7% (placebo), 6% (0.5 mg), 0% (4 mg), 9% (8 mg), 3% (12 mg), and 0% (dulaglutide). Gastrointestinal events were most frequent, and no deaths were reported.
Why it matters
Retatrutide significantly reduces total fat mass at higher doses in adults with type 2 diabetes without disproportionate lean mass loss relative to other obesity treatments.
Limits
Substantial scan attrition occurred: of 189 enrolled, only 155 had baseline DXA scans and 103 completed both baseline and week 36 scans. The sample was predominantly White (85%), and specific numerical changes for lean mass were omitted from the abstract.
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