REDEFINE 5: CagriSema versus semaglutide in Japan and Taiwan

Why this study matters

CagriSema is an experimental combination of two medicines. It is not approved in Canada as of September 2026, and this study is research only. It combines cagrilintide, a long-acting version of the hormone amylin, with semaglutide (Wegovy, Ozempic), a GLP-1 receptor agonist. Unlike the larger REDEFINE 1 and 2 trials, which compared the combination mainly with placebo, REDEFINE 5 compared it head to head with semaglutide alone. It also enrolled an East Asian population using Japanese criteria for obesity treatment, which are different from the criteria used in North American trials. That makes it useful and also limits how far the results travel.

Who was in the study

The trial enrolled 331 adults aged 18 or older at 21 sites in Japan and one site in Taiwan. To take part, people needed a BMI of at least 27 with at least two obesity-related complications, or a BMI of at least 35 with at least one complication, following the Japan Society for the Study of Obesity guidelines. BMI, or body mass index, is weight in kilograms divided by height in metres squared. People with or without type 2 diabetes could join, and 80 participants (24%) had type 2 diabetes. Of the participants, 226 (68%) were male and 105 (32%) were female. The trial ran for 68 weeks.

What the researchers did

This was a phase 3a, randomized, double-blind, active-controlled trial. Randomized means people were assigned to groups by chance. Double-blind means participants, site staff, investigators and the study funder did not know who was on which active treatment. Active-controlled means the comparison was with a real medicine rather than a placebo.

Participants were assigned in equal numbers to once-weekly injections of cagrilintide-semaglutide (164 people) or semaglutide alone (167 people), both escalated to 2.4 mg, plus a lifestyle intervention, for 68 weeks. The primary end point was the relative change in body weight from the start to week 68.

The main analysis used the trial-product estimand. An estimand is the precise question the statistics answer. This one estimates the effect assuming the treatment was taken as intended, regardless of dose. Missing values at week 68 were filled in using statistical imputation. This is a different question from the treatment-policy estimand used in REDEFINE 1 and 2, which counts everyone regardless of whether they stayed on treatment.

What they found

At week 68, the estimated average change in body weight was -18.4% in the cagrilintide-semaglutide group and -11.9% in the semaglutide group. The estimated difference was -6.5 percentage points (95% confidence interval -8.4 to -4.6), with P below 0.0001. A confidence interval is the range of values the data are reasonably consistent with (R32-C78).

The published summary we reviewed does not report results for people with and without diabetes separately, or the share of people who reached weight-loss targets.

Side effects and people who stopped

Adverse events were reported by 143 of 164 people (87%) in the combination group and 141 of 167 (84%) in the semaglutide group. The most common were gastrointestinal disorders, meaning stomach and bowel symptoms, reported by 87 of 164 (53%) in the combination group and 85 of 167 (51%) in the semaglutide group. One death was reported, in the semaglutide group, and the investigator did not judge it to be related to treatment.

During the trial, 17 people (10%) stopped cagrilintide-semaglutide and 10 people (6%) stopped semaglutide. The published summary we reviewed does not say how many of these stopped because of side effects.

What this study does not tell you

• CagriSema is not approved in Canada as of September 2026.
• The trial used Japanese obesity criteria and enrolled people in Japan and Taiwan. The results may not apply directly to a Canadian population.
• The trial-product estimand estimates what happens if the treatment is taken as intended. It is not an estimate of what happens when the medicine is prescribed to everyone, including people who stop.
• Groups were relatively small, at 164 and 167 people, so uncommon harms could not be detected.
• The trial ran for 68 weeks and does not show what happens after that or when the injections stop.
• Our summary is based on the abstract only. Results by diabetes status, and stopping for side effects, are not available to us.
• Do not compare these figures with REDEFINE 1 or other trials. The estimand, the population and the entry criteria all differ.
• The trial was funded by the company developing the combination.

What it means in Canada

CagriSema is not approved in Canada as of September 2026. Semaglutide on its own is covered on our semaglutide in Canada page. For emerging medicines, see our medicines page. For how weight-management medicines are paid for, see public drug coverage by province.

Related reading

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

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