Phase 2 Body Composition Substudy
Phase 2 Body Composition Substudy
DXA scans from the Phase 2 type 2 diabetes trial: fat mass fell 26.1% on 8 mg and 23.2% on 12 mg at 36 weeks, vs 4.5% on placebo.
Phase 2 Body Composition Substudy — DXA scans from the Phase 2 type 2 diabetes trial: fat mass fell 26.1% on 8 mg and 23.2% on 12 mg at 36 weeks, vs 4.5% on placebo.
Trial Facts
| Property | Value |
|---|---|
| Trial Name | Phase 2 Body Composition Substudy |
| Phase | 2 |
| Status | results-published |
| Enrollment | 189 participants |
| NCT ID | NCT04867785 |
| Completion | July 8, 2022 |
| Conditions | type 2 diabetes, overweight, obesity |
| Primary Endpoints | Percent change in total body fat mass from baseline to week 36 (DXA) |
Primary Endpoints
- Percent change in total body fat mass from baseline to week 36 (DXA)
Study Overview
This substudy used dual-energy X-ray absorptiometry (DXA) to measure changes in fat mass and lean mass during retatrutide treatment. It was part of the Phase 2 type 2 diabetes trial (NCT04867785), not the Phase 2 obesity trial. It was published by Coskun et al. in The Lancet Diabetes & Endocrinology (online June 30, 2025; 2025;13(8):674-684). No body composition results have been published from the Phase 2 obesity trial.
Why Body Composition Matters
One of the key concerns with pharmacological weight loss is the preservation of lean body mass (muscle and bone). Ideally, weight loss agents should preferentially reduce fat mass while keeping lean mass loss small.
Study Design
- Population: adults aged 18-75 with type 2 diabetes, HbA1c 7.0-10.5% and BMI 25-50 kg/m², at 42 US centres
- Arms: placebo, dulaglutide 1.5 mg, or retatrutide 0.5 mg, 4 mg, 8 mg or 12 mg (the two 4 mg and two 8 mg regimens were pooled)
- Size: 189 participants enrolled in the substudy; 155 had a baseline scan and 103 finished treatment with scans at baseline and week 36
- Primary substudy endpoint: percent change in total fat mass from baseline to week 36
Results
Total Fat Mass at 36 Weeks
| Group | Fat mass change | Difference from placebo |
|---|---|---|
| Placebo | -4.5% | — |
| Dulaglutide 1.5 mg | -2.6% | — |
| Retatrutide 0.5 mg | -4.9% | -0.4 (not significant) |
| Retatrutide 4 mg (pooled) | -15.2% | -10.7 |
| Retatrutide 8 mg (pooled) | -26.1% | -21.6 |
| Retatrutide 12 mg | -23.2% | -18.7 |
Retatrutide at 4 mg and above reduced fat mass significantly more than placebo and dulaglutide.
Lean Mass
Lean mass also fell. The authors concluded that the proportion of lean mass lost relative to total weight lost was similar to that seen with other obesity treatments, and that a greater share of lean mass was not lost with retatrutide despite the larger weight loss. We have not listed a fat-to-lean ratio or visceral fat figures, because we could not confirm them against the paper.
Limitations
- Only 103 of 189 enrolled participants had both baseline and week 36 scans while still on treatment
- People with type 2 diabetes only; results may differ in people without diabetes
- 36 weeks of treatment, shorter than the Phase 3 trials (68 to 80 weeks)
Publication
Coskun T, Wu Q, Schloot NC, Haupt A, Milicevic Z, Khouli C, Harris C. 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. The Lancet Diabetes & Endocrinology. 2025;13(8):674-684. doi:10.1016/S2213-8587(25)00092-0
Sources Used On This Page
- 1coskun-2025-lancet-de
- 2rosenstock-2023-lancet