{"id":"262f725f1d71","type":"article","url":"https://hartvaat.nl/2025/08/14/cagrisema-gecombineerd-cagrilintide-en-semaglutide-bij-overgewicht-nejm/","title":"CagriSema: gecombineerd cagrilintide en semaglutide bij overgewicht — NEJM","title_en":"Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.","category":"cholesterol","category_label":"Cholesterol","professions":["apotheker","cardioloog","huisarts","internist"],"tags":["cagrisema","select-trial","semaglutide","soul-trial","tirzepatide"],"journal":"The New England journal of medicine","doi":"10.1056/NEJMoa2502081","source_url":"https://doi.org/10.1056/NEJMoa2502081","authors":["W Timothy Garvey","Matthias Blüher","Cynthia Karenina Osorto Contreras","Melanie J Davies","Eva Winning Lehmann","Kirsi H Pietiläinen","Domenica Rubino","Paolo Sbraccia","Thomas Wadden","Niels Zeuthen","John P H Wilding"],"significance":10,"published":"2025-08-14","source_date":"2025-08-14","image":"","kennis":["https://hartvaat.nl/kennis/lipiden/ezetimib/","https://hartvaat.nl/kennis/farmacologie/glp1-agonisten-cardiologie/"],"congress":"","summary_en":"This pivotal trial of CagriSema (cagrilintide plus semaglutide) in adults with overweight or obesity demonstrated up to 25% body weight reduction, substantially exceeding semaglutide monotherapy. The amylin–GLP-1 combination represents the most effective pharmacological weight loss therapy to date and may redefine obesity treatment targets.","created":"2026-07-03T10:31:48Z","updated":"2026-07-03T13:30:48Z","licence":"Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.","body_markdown":"NEJM-trial van CagriSema (amyline-analoog + GLP-1-agonist) toonde spectaculair gewichtsverlies tot 25% bij overgewicht/obesitas. De combinatie overtreft semaglutide monotherapie en markeert de volgende generatie obesitasbehandeling.","abstract_original":"BACKGROUND: 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. METHODS: 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. CONCLUSIONS: Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.)."}