A once-weekly combination of cagrilintide and semaglutide delivered striking results in a global phase 3 trial of adults with overweight or obesity.
In the 68-week phase 3 REDEFINE 1 trial, 3,417 adults without diabetes and with a BMI of at least 30—or 27 with an obesity-related condition—were randomized to receive the fixed-dose combination (CagriSema), semaglutide alone, cagrilintide alone, or placebo. All participants received lifestyle counseling.
CagriSema was delivered once weekly using a dual-chamber pen. Doses of each drug were escalated over 16 weeks to maintenance doses of 2.4 mg.
By week 68, participants in the CagriSema group had a mean weight loss of 20.4%, compared with 3% in the placebo group. The estimated difference between groups was –17.3 percentage points (95% confidence interval = –18.1 to –16.6; P < .001). Among those who received CagriSema, 91.9% lost at least 5% of their body weight, 53.6% lost 20% or more, and 19.3% lost at least 30%.
Semaglutide alone resulted in a 14.9% mean weight loss, while cagrilintide alone resulted in an 11.5% reduction.
Participants on CagriSema also showed metabolic improvements. Systolic blood pressure decreased by 9.9 mm Hg, and 87.7% of participants with baseline prediabetes achieved normoglycemia by week 68, compared with 32.2% in the placebo group.
In a DXA substudy, 67% of weight loss in the CagriSema group was from fat mass and 33% from lean tissue.
Gastrointestinal adverse events were the most common side effects, which affectied 79.6% of the CagriSema group. These events included nausea, vomiting, and diarrhea, were typically mild or moderate, and occurred most frequently during dose escalation. The discontinuation rate due to adverse events was 5.9%.
Two deaths occurred in the CagriSema group, one due to cancer and one to suicide. Serious adverse events were reported in 9.8% of participants who received the combination, compared with lower rates in the other groups.
The REDEFINE 1 trial supports the use of CagriSema for weight management in adults without diabetes. A follow-up study is ongoing to evaluate its use in adults with type 2 diabetes.
Full disclosures can be found in the published study.