Amylin + GLP‑1 hits >20%

A weekly two-drug obesity shot pushed average weight loss past 22% in a 68-week phase 3 trial, with 60% of patients losing at least 20%. (nejm.org) The regimen combines semaglutide, a glucagon-like peptide-1 drug that reduces appetite and slows stomach emptying, with cagrilintide, an amylin analog that also helps people feel full after eating. In REDEFINE 1, 3,417 adults with obesity or overweight plus at least one weight-related condition were randomized to the combination, either drug alone, or placebo. (nejm.org) At 68 weeks, the estimated mean weight change was -20.4% with the combination, versus -3.0% with placebo, in the trial’s primary analysis. In a treatment-policy analysis that counted all participants regardless of whether they stayed on therapy, the mean reduction was 13.7%; in an on-treatment analysis, it was 22.7%. (nejm.org) The study was published in The New England Journal of Medicine on June 22, 2025, and presented the same week at the American Diabetes Association’s 85th Scientific Sessions. Novo Nordisk filed a U.S. Food and Drug Administration application for the drug, branded CagriSema, on December 18, 2025. (nejm.org) (prnewswire.com) Obesity drugs already on the market, including semaglutide alone, have set a new bar for medical weight loss, but combination therapies are being tested to push results closer to what surgery can achieve in some patients. The American College of Cardiology said REDEFINE 1 and REDEFINE 2 showed greater weight loss with the combined shot than with placebo or either component alone. (acc.org) The combination also improved waist circumference, blood pressure, blood sugar markers, and lipids more than placebo in REDEFINE 1. Gastrointestinal side effects were the most common problem, and most were mild to moderate, though 8.4% of patients on the combination stopped treatment because of adverse events, versus 3.8% on placebo. (nejm.org) Results were weaker when patients did not stay on the drug, a gap that has become central in obesity medicine because nausea, cost, and long-term adherence can all limit real-world use. Applied Clinical Trials reported that 23% of REDEFINE 1 participants on the combination lost at least 30% of body weight. (appliedclinicaltrialsonline.com) (nejm.org) The next step is regulatory review, not a new efficacy readout: as of April 17, 2026, the public milestone after the June 2025 data is Novo Nordisk’s December 2025 FDA filing. The question now is whether the trial’s weight-loss numbers hold up against the practical test of tolerability, access, and long-term use. (prnewswire.com)