Retatrutide phase 2: weight change over 48 weeks in adults

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 three hormone receptors at once: GIP, GLP-1 and glucagon. Medicines available in Canada act on one (semaglutide) or two (tirzepatide) of these. This trial was the first mid-stage test of whether the triple approach produces more weight loss, and at what cost in side effects. The large numbers reported here have drawn a lot of attention, so it is worth understanding exactly what was and was not shown.

Who was in the study

The trial enrolled 338 adults, and 51.8% of them were men. To take part, people needed a BMI of 30 or higher, or a BMI of 27 to under 30 plus at least one weight-related condition. BMI, or body mass index, is weight in kilograms divided by height in metres squared. The published summary we reviewed does not report the age range or the countries where the trial was run, and it does not say whether people with diabetes were excluded. The trial ran for 48 weeks.

What the researchers did

This was a phase 2, double-blind, randomized, placebo-controlled trial. Phase 2 means a mid-stage trial designed to find the right doses. Randomized means people were assigned to a group by chance. Double-blind means neither participants nor study staff knew who was on the medicine. A placebo is an inactive injection that looks the same as the real one.

Participants received a weekly injection of retatrutide or placebo for 48 weeks. There were six retatrutide groups: 1 mg; 4 mg with a starting dose of 2 mg; 4 mg with a starting dose of 4 mg; 8 mg with a starting dose of 2 mg; 8 mg with a starting dose of 4 mg; and 12 mg with a starting dose of 2 mg. Groups were assigned in a 2:1:1:1:1:2:2 ratio. The primary end point, meaning the main result the trial was built to measure, was the percentage change in body weight at 24 weeks. Weight change at 48 weeks, and the share of people losing at least 5%, 10% or 15%, were secondary end points. The published summary we reviewed does not describe the lifestyle support the groups received.

What they found

At 24 weeks, the primary time point, the average change in body weight was -7.2% in the 1 mg group, -12.9% in the combined 4 mg groups, -17.3% in the combined 8 mg groups and -17.5% in the 12 mg group, compared with -1.6% with placebo.

At 48 weeks, the secondary time point, the averages were -8.7% at 1 mg, -17.1% at 4 mg, -22.8% at 8 mg and -24.2% at 12 mg, compared with -2.1% with placebo (R32-C71).

The trial also reported how many people reached weight-loss thresholds at 48 weeks. Of those taking 4 mg, 92% lost at least 5%, 75% lost at least 10% and 60% lost at least 15%. At 8 mg the figures were 100%, 91% and 75%. At 12 mg they were 100%, 93% and 83%. With placebo they were 27%, 9% and 2%.

The published summary we reviewed does not report a between-group difference with a confidence interval, so we cannot give one here.

Side effects and people who stopped

The most common side effects in the retatrutide groups were gastrointestinal, meaning stomach and bowel symptoms. These were dose related and mostly mild to moderate. They were partly reduced by starting at 2 mg rather than 4 mg. Heart rate rose in a dose-dependent way, peaked at 24 weeks and then declined. The published summary we reviewed does not report how many people stopped treatment or left the trial, or how many stopped because of side effects.

What this study does not tell you

• This is phase 2 evidence. The 48-week weight results are a secondary outcome, and the trial was designed to find doses, not to confirm benefit or safety.
• Retatrutide is not approved in Canada as of September 2026.
• A trial of 338 people cannot detect rare harms, and 48 weeks says nothing about longer-term safety, including the heart-rate increase the authors observed.
• The summary does not report how many people dropped out, so we cannot judge how complete the data were.
• It does not tell you what happens to weight when the injections stop.
• Do not compare these percentages with numbers from trials of other medicines. Different trials enrol different people and use different methods.
• The trial was funded by the company that makes the medicine.

What it means in Canada

Retatrutide is not approved in Canada as of September 2026. This trial is part of the research record for a medicine that is still in development. 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 for how they are paid for.

Related reading

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

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