Retatrutide in type 2 diabetes: a 36-week phase 2 trial

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: GIP, GLP-1 and glucagon. Current diabetes guidance treats weight management as being as important as reaching blood sugar targets. This trial asked whether retatrutide can do both in people with type 2 diabetes, and it compared the new medicine not only with placebo but with dulaglutide, an existing weekly GLP-1 injection. Its results were used to choose the doses for the later phase 3 program.

Who was in the study

The trial enrolled 281 adults aged 18 to 75 with type 2 diabetes. Their HbA1c was between 7.0% and 10.5%, and their BMI was between 25 and 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. Before joining, people had been managing their diabetes with diet and exercise alone, or with a stable dose of metformin of at least 1000 mg a day, for at least three months.

The average age was 56.2 years, the average time since diabetes diagnosis was 8.1 years, 56% were female and 84% were White. The trial was run at 42 research and health-care centres in the USA.

What the researchers did

This was a randomized, double-blind, phase 2 trial with both a placebo and an active comparator. Randomized means people were assigned to groups by chance. Double-blind means neither participants nor staff knew who was getting which treatment. A placebo is an inactive injection. The active comparator was dulaglutide 1.5 mg weekly.

There were eight groups: placebo (45 people), dulaglutide 1.5 mg (46), and retatrutide at 0.5 mg (47), 4 mg with escalation from 2 mg (23), 4 mg with no escalation (24), 8 mg with slow escalation (26), 8 mg with fast escalation (24) and 12 mg with escalation (46). Six people were enrolled by mistake and left out of the efficacy analysis, which included 275 people. Safety was assessed in everyone who received at least one dose. The primary end point, meaning the main result, was the change in HbA1c at 24 weeks. Weight change at 36 weeks was a secondary end point.

What they found

At 24 weeks, HbA1c fell with every retatrutide dose above the lowest. The changes were -0.43% at 0.5 mg, -1.39% at 4 mg with escalation, -1.30% at 4 mg without escalation, -1.99% at 8 mg slow escalation, -1.88% at 8 mg fast escalation and -2.02% at 12 mg. Placebo changed by -0.01% and dulaglutide by -1.41%. The reductions with retatrutide were significantly greater than placebo in all but the 0.5 mg group, and greater than dulaglutide in the 8 mg slow-escalation and 12 mg groups. Findings were consistent at 36 weeks.

Body weight at 36 weeks fell in a dose-dependent way (R32-C73):

For retatrutide doses of 4 mg and above, the weight decreases were significantly greater than with placebo and with dulaglutide. The published summary we reviewed does not report between-group differences with confidence intervals, so we cannot give them here.

Side effects and people who stopped

Mild to moderate gastrointestinal side effects, including nausea, diarrhoea, vomiting and constipation, were reported by 67 of 190 people (35%) across the retatrutide groups. The rate ranged from 6 of 47 (13%) at 0.5 mg to 12 of 24 (50%) in the 8 mg fast-escalation group. The rate was 6 of 45 (13%) with placebo and 16 of 46 (35%) with dulaglutide. There were no reports of severe hypoglycaemia (low blood sugar) and no deaths.

Overall, 237 people (84%) completed the study and 222 (79%) completed the study treatment. The published summary we reviewed does not break these figures down by group, and does not report how many people stopped because of side effects.

What this study does not tell you

• This is a short phase 2 trial with small groups, some of only 23 or 24 people. Estimates for individual dose groups are imprecise.
• Weight was a secondary outcome. The trial was built to test HbA1c.
• Retatrutide is not approved in Canada as of September 2026.
• All sites were in the USA, and 84% of participants were White. Results may differ in other populations.
• Results depend on the dose and on how quickly the dose was raised, so no single number describes "retatrutide".
• About one in five people did not complete treatment, and the summary does not say why or which groups they were in.
• Do not compare these figures with numbers from other trials, including trials of other medicines in type 2 diabetes.
• 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. This trial describes 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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