Add on Cagrilintide to Semaglutide tied to Significant Weight Loss in diabetics and non diabetics in Obesity Trials

Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the combination (known as CagriSema) on weight loss in persons with either overweight and coexisting conditions or obesity is unknown.

In a phase 3a, 68-week, multicenter, double-blind, placebo-controlled and active-controlled trial, we enrolled adults without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. Participants were randomly assigned in a ratio of 21:3:3:7 to receive the combination of semaglutide at a dose of 2.4 mg and cagrilintide at a dose of 2.4 mg, semaglutide alone at a dose of 2.4 mg, cagrilintide alone at a dose of 2.4 mg, or placebo, plus lifestyle interventions for all groups.

The coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide–semaglutide as compared with placebo. Body-weight reductions of 20% or more, 25% or more, and 30% or more were assessed as confirmatory secondary end points. Effect estimates were assessed with the treatment-policy estimand (consistent with the intention-to-treat principle). Safety was assessed.

Results: A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide–semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo.

The estimated mean percent change in body weight from baseline to week 68 was –20.4% with cagrilintide–semaglutide as compared with –3.0% with placebo (estimated difference, –17.3 percentage points; 95% confidence interval, –18.1 to –16.6; P<0.001). Participants receiving cagrilintide–semaglutide were more likely than those receiving placebo to reach weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons).

Gastrointestinal adverse events (affecting 79.6% in the cagrilintide–semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity. Cagrilintide–semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo.

Reference:

Melanie J. Davies,Harpreet S. Bajaj,Christa Broholm,Astrid Eliasen,W. Timothy Garvey,Carel W. le Roux,Ildiko Lingvay,Christian Bøge Lyndgaard,Julio Rosenstock,Sue D. Pedersen,Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes, New England Journal of Medicine, 0, 0, (undefined). /doi/full/10.1056/NEJMoa2502082