CagriSema trials show 20.4% and 13.7% average weight loss in two phase 3 studies

Two phase 3 trials of CagriSema, an investigational once-weekly combination of cagrilintide and semaglutide, produced average weight losses of 20.4% in adults with overweight or obesity and no diabetes, and 13.7% in adults with type 2 diabetes, both measured at 68 weeks ^[1][2]. Semaglutide is the molecule in Ozempic, Wegovy and Rybelsus; cagrilintide is a separate compound paired with it in this combination ^[1][2].

The first trial, REDEFINE 1, enrolled 3,417 adults without diabetes who had a body-mass index of 30 or higher, or 27 or higher with at least one weight-related complication ^[1]. Participants were assigned at random to CagriSema (2,108 people), semaglutide 2.4 mg alone (302), cagrilintide 2.4 mg alone (302) or placebo (705), and everyone also received lifestyle intervention ^[1]. The estimated average change in body weight at week 68 was -20.4% with CagriSema versus -3.0% with placebo, an estimated difference of -17.3 percentage points (95% confidence interval, -18.1 to -16.6; P<0.001) ^[1]. People taking CagriSema were more likely than those on placebo to reach weight-loss targets of 5%, 20%, 25% and 30% (P<0.001 for every comparison) ^[1]. The abstract does not report how the semaglutide-only or cagrilintide-only arms performed, so the head-to-head comparisons built into the trial have not been disclosed in this publication ^[1].

The second trial, REDEFINE 2, was run in 12 countries and enrolled 1,206 adults with type 2 diabetes, a body-mass index of 27 or higher, and a glycated hemoglobin level between 7% and 10% ^[2]. They were assigned in a 3:1 ratio to CagriSema at 2.4 mg of each drug (904 people) or placebo (302), alongside lifestyle intervention, for 68 weeks ^[2]. Average weight change was -13.7% with CagriSema and -3.4% with placebo, a difference of -10.4 percentage points (95% confidence interval, -11.2 to -9.5; P<0.001) ^[2]. On blood sugar, 73.5% of the CagriSema group reached a glycated hemoglobin level of 6.5% or lower, compared with 15.9% of the placebo group ^[2]. More people on CagriSema also reached weight reductions of at least 5%, 10%, 15% and 20% ^[2].

Gastrointestinal side effects were the most commonly reported problem in both trials. In REDEFINE 1, they affected 79.6% of people taking CagriSema and 39.9% of those on placebo; in REDEFINE 2, the figures were 72.5% and 34.4% ^[1][2]. These events included nausea, vomiting, diarrhea, constipation and abdominal pain, and were described as mainly transient and mild-to-moderate in severity ^[1][2]. Both studies were funded by Novo Nordisk, and both reported their results using the treatment-policy estimand, which is consistent with analyzing everyone as originally assigned ^[1][2].

Why it matters for patients

CagriSema is not described as an approved medicine in either report, and neither publication states when or whether it might become available in the United States ^[1][2]. People weighing their options today are choosing among products that are already on the market, including semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound).

The numbers reported are group averages, not predictions for any one person, and they come from research volunteers who also received lifestyle intervention throughout the trials ^[1][2]. Weight change beyond 68 weeks of treatment is not addressed in either report. The reported side-effect rates are also notable: about 8 in 10 participants on CagriSema in REDEFINE 1 reported a gastrointestinal event ^[1].

One practical gap is that REDEFINE 1 included a semaglutide-only arm at the same 2.4 mg dose used in Wegovy, but the abstract does not report that comparison, so how the combination stacks up against semaglutide alone has not been established in these publications ^[1].

What happens next

No regulatory submission dates, approval decisions or launch timelines are disclosed in either publication ^[1][2]. Both trials are registered on ClinicalTrials.gov, REDEFINE 1 as NCT05567796 and REDEFINE 2 as NCT05394519, for readers who want to track later updates ^[1][2]. The journal that published the trials also carried several letters and author replies about the results in a later issue ^[1].