Retatrutide and body fat: a DXA substudy in type 2 diabetes

Why this study matters

Retatrutide is an experimental medicine. It is not approved in Canada as of September 2026, and this study is research only. It acts on GIP, GLP-1 and glucagon receptors. When people lose a lot of weight, a common concern is how much of that weight is fat and how much is lean mass such as muscle. This substudy used body scans to look inside the weight numbers from the retatrutide phase 2 trial in type 2 diabetes. It is one of the few sources of body-composition data for this medicine.

Who was in the study

The parent trial enrolled 281 adults aged 18 to 75 with type 2 diabetes, HbA1c of 7.0 to 10.5%, stable body weight, and a BMI of 25 to 50. HbA1c is a blood test that reflects average blood sugar over about three months. BMI, or body mass index, is weight in kilograms divided by height in metres squared. Of those 281 people, 189 joined the body-composition substudy. Of the substudy participants, 56% were female, 85% were White, 13% were Black and 3% were Asian. The trial ran at 42 medical centres in the USA and lasted 36 weeks.

What the researchers did

This was a prespecified substudy of a phase 2, randomized, double-blind, placebo-controlled trial. Prespecified means the body-composition question was planned before the trial began. Randomized means people were assigned to groups by chance. Double-blind means neither participants nor staff knew who was on which treatment. A placebo is an inactive injection. Dulaglutide 1.5 mg weekly, an existing GLP-1 medicine, was the active comparator.

Substudy participants were spread across the groups: 29 on placebo, 32 on retatrutide 0.5 mg, 31 on retatrutide 4 mg (two starting-dose groups pooled), 33 on retatrutide 8 mg (two starting-dose groups pooled), 30 on retatrutide 12 mg and 34 on dulaglutide 1.5 mg. The primary substudy end point was the percentage change in total fat mass from the start to week 36, measured by DXA. DXA is a low-dose X-ray scan that estimates how much of the body is fat, lean tissue and bone.

The analysis used on-treatment data collected before anyone stopped the study drug, from randomized participants who had DXA scans. This is a different approach from an intention-to-treat analysis: it describes the effect while people stayed on the medicine.

What they found

Of the 189 people enrolled in the substudy, 155 had a baseline DXA scan and 103 completed treatment and had both the baseline and week 36 scans.

The percentage reduction in total fat mass at 36 weeks was 4.9% with retatrutide 0.5 mg, 15.2% with 4 mg, 26.1% with 8 mg and 23.2% with 12 mg, compared with 2.6% with dulaglutide and 4.5% with placebo (R32-C75).

Compared with placebo, the difference in fat-mass change was -0.4 percentage points (95% confidence interval -4.0 to 3.2) with 0.5 mg, -10.7 (95% CI -17.2 to -4.2) with 4 mg, -21.6 (95% CI -27.1 to -16.1) with 8 mg and -18.7 (95% CI -25.1 to -12.3) with 12 mg. A confidence interval is the range of values the data are reasonably consistent with. The 0.5 mg result includes zero, so that dose could not be shown to differ from placebo.

The authors state that the share of weight lost as lean mass was similar to other obesity treatments. The published summary we reviewed does not give a number for lean-mass change, so this page does not report one.

Side effects and people who stopped

The authors report that adverse events were similar between groups, and gastrointestinal events (stomach and bowel symptoms) were the most common. Serious adverse events occurred in 2 of 29 people (7%) on placebo, 2 of 32 (6%) on retatrutide 0.5 mg, 0 of 31 on 4 mg, 3 of 33 (9%) on 8 mg, 1 of 30 (3%) on 12 mg and 0 of 34 on dulaglutide. No deaths were reported. The published summary we reviewed does not report how many people stopped treatment or why.

What this study does not tell you

• Only 103 of 189 substudy participants completed treatment and both scans. Losing about half of the scans may bias the estimates, and the summary does not say who was missing.
• The analysis describes the effect while people stayed on the medicine. It does not describe what happens after stopping.
• Groups were small, around 30 people each, so estimates are imprecise.
• No numerical lean-mass result is available to us. The reassuring statement about lean mass is the authors' interpretation, not a figure we can check.
• Retatrutide is not approved in Canada as of September 2026.
• All sites were in the USA, and 85% of participants were White.
• Do not compare these fat-mass figures with body-composition results from trials of other medicines.
• The trial was funded by the company developing the medicine.

What it means in Canada

Retatrutide is not approved in Canada as of September 2026, and this substudy adds detail to a medicine that is still being studied. You can follow emerging medicines on our medicines page. For medicines available in Canada, see semaglutide in Canada and tirzepatide in Canada, and public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

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