REDEFINE 1: CagriSema for weight loss over 68 weeks

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. The two parts are cagrilintide, a long-acting version of the hormone amylin, and semaglutide (Wegovy, Ozempic), a GLP-1 receptor agonist that is already used in Canada. REDEFINE 1 is the large phase 3 trial that tested the combination against placebo and against each medicine on its own. Phase 3 trials are what regulators review, so this is the study most likely to shape any future decision about the combination in Canada.

Who was in the study

The trial enrolled 3417 adults without diabetes. They had a BMI of 30 or higher, or a BMI of 27 or higher with at least one obesity-related complication. BMI, or body mass index, is weight in kilograms divided by height in metres squared. The trial ran for 68 weeks at multiple centres. The published summary we reviewed does not report the age range, the countries, or the average starting weight.

What the researchers did

This was a phase 3a, randomized, double-blind trial with both placebo and active comparison groups. 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.

Participants were assigned in a 21:3:3:7 ratio to four groups: cagrilintide 2.4 mg plus semaglutide 2.4 mg (2108 people), semaglutide 2.4 mg alone (302), cagrilintide 2.4 mg alone (302) or placebo (705). Every group also received lifestyle interventions. The two primary end points were the percentage change in body weight and the share of people losing at least 5% of their body weight from the start to week 68, comparing the combination with placebo. Losing at least 20%, 25% or 30% were confirmatory secondary end points.

The results were analysed with the treatment-policy estimand, which is consistent with the intention-to-treat principle. An estimand is the precise question the statistics answer. This one counts everyone who was randomized, whether or not they kept taking the injections, so it reflects what happens when the treatment is prescribed rather than only among people who stay on it.

What they found

At week 68, the estimated average change in body weight was -20.4% with the combination and -3.0% with placebo. The estimated difference was -17.3 percentage points (95% confidence interval -18.1 to -16.6), with P below 0.001. A confidence interval is the range of values the data are reasonably consistent with (R32-C66).

People on the combination were more likely than people on placebo to reach weight-loss targets of at least 5%, 20%, 25% and 30%, with P below 0.001 for each comparison. The published summary we reviewed does not give the percentages of people who reached each target.

The summary also does not report the weight results for the semaglutide-alone or cagrilintide-alone groups, so this page cannot say how the combination compared with either medicine on its own.

Side effects and people who stopped

Gastrointestinal adverse events, meaning stomach and bowel symptoms such as nausea, vomiting, diarrhoea, constipation or abdominal pain, affected 79.6% of people in the combination group and 39.9% of people in the placebo group. Most were temporary and mild to moderate in severity (R32-C67). The published summary we reviewed does not report how many people stopped treatment, or how many stopped because of side effects.

What this study does not tell you

• CagriSema is not approved in Canada as of September 2026.
• The abstract reports results for the combination and placebo only. We cannot tell you from this summary how much the combination added beyond semaglutide alone.
• People with diabetes were excluded. REDEFINE 2 covers that group separately.
• The trial ran for 68 weeks and does not show what happens after that, or what happens when the injections stop.
• Stopping rates are not in the summary we reviewed, so we cannot say how many people found the side effects hard to tolerate.
• The intention-to-treat analysis includes people who stopped the injections, so the effect among people who kept taking them may differ.
• Do not compare the -20.4% figure with results from other trials. Different trials enrol different people and use different methods.
• 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 a different matter, and you can read about it 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, and to see how services differ, visit compare services.

Related reading

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

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