TRANSCEND-T2D-1: retatrutide alone in early 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 three hormone receptors: GIP, GLP-1 and glucagon. TRANSCEND-T2D-1 is the first phase 3 trial of retatrutide in type 2 diabetes to be published. It tested the medicine on its own, in people whose diabetes was not controlled by diet and exercise and who were not taking any diabetes medicine. Phase 3 trials are what regulators review, so this study matters for any future decision about the medicine in Canada.

Who was in the study

The trial enrolled 537 adults aged 18 or older with type 2 diabetes that was inadequately controlled by diet and exercise alone. Their HbA1c was between 7.0% and 9.5%, and their BMI was at least 23. 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.

At the start, the average age was 48.8 years, the average HbA1c was 7.9%, the average time since diabetes diagnosis was 2.5 years and the average BMI was 35.8. Of the participants, 55% were female. The trial ran for 40 weeks at 48 sites in the USA, Mexico and India.

What the researchers did

This was a phase 3, randomized, double-blind, placebo-controlled trial. Randomized means people were assigned to groups by chance. Double-blind means neither participants nor staff knew who was getting the medicine. A placebo is an inactive injection.

Participants were assigned in equal numbers to once-weekly retatrutide at 4 mg (134 people), 9 mg (133), or 12 mg (136), or placebo (134). The primary end point, meaning the main result the trial was designed to test, was the change in HbA1c from the start to week 40. The percentage change in body weight was a key secondary end point. The main analysis used the treatment-regimen estimand. An estimand is the precise question the statistics answer. This one counts everyone who was randomized, whether or not they stayed on the injections. The published summary we reviewed does not describe the lifestyle support the groups received.

What they found

At week 40, the average change in HbA1c was -1.69% with retatrutide 4 mg, -1.86% with 9 mg and -1.94% with 12 mg, compared with -0.81% with placebo. The estimated differences from placebo were -0.88% (95% confidence interval -1.18 to -0.59) for 4 mg, -1.04% (95% CI -1.32 to -0.76) for 9 mg and -1.12% (95% CI -1.39 to -0.85) for 12 mg, each with P below 0.0001. A confidence interval is the range of values the data are reasonably consistent with.

Body weight, the key secondary outcome, changed by -11.5% with 4 mg, -13.9% with 9 mg and -15.3% with 12 mg, compared with -2.6% with placebo (R32-C72).

The published summary we reviewed does not report a between-group difference in weight with a confidence interval.

Side effects and people who stopped

The most frequent side effects with retatrutide were gastrointestinal events, meaning stomach and bowel symptoms. They were generally mild to moderate and subsided over time. Stopping the study medicine because of side effects occurred in 2 to 5% of people across the retatrutide groups and 0% of the placebo group. The published summary we reviewed does not give the rate for each dose. No severe hypoglycaemia (low blood sugar) was reported. Two deaths occurred during the study, both in the retatrutide 4 mg group, and both were judged unrelated to the study drug.

Overall, 490 people (91%) completed the treatment period on the study drug and 504 (94%) completed the study. The summary does not break these figures down by group.

What this study does not tell you

• Retatrutide is not approved in Canada as of September 2026.
• Weight was a secondary outcome. The trial was designed around HbA1c, in people with early diabetes not yet on medicines.
• The trial ran for 40 weeks. It does not show longer-term blood sugar control, weight, or safety, and it does not show what happens after stopping.
• The results describe retatrutide on its own. They do not describe adding it to metformin, insulin or other treatments.
• Sites were in the USA, Mexico and India. The summary does not say how the results might apply to other populations.
• Our summary is based on the abstract only. Stopping rates by dose and lifestyle support are not available to us.
• Do not compare these figures with results from trials of other medicines in type 2 diabetes. Different trials enrol different people and use different methods.
• 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 is part of the evidence a regulator would consider, but no Canadian approval has followed as of our review date. 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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