Novo Nordisk files for FDA approval of CagriSema, a combined GLP-1 and amylin obesity drug
A once-weekly combination obesity injection has been filed for FDA review, adding an amylin mechanism to semaglutide, though it is unapproved and side effects were common in trials.
Novo Nordisk said on Dec. 18, 2025 that it has filed a New Drug Application with the U.S. Food and Drug Administration for CagriSema, a once-weekly injection it wants approved to reduce excess body weight and maintain weight loss long term in adults who have obesity, or who are overweight with at least one weight-related condition [3].
CagriSema is a fixed-dose combination of cagrilintide 2.4 mg, a long-acting amylin analog, and semaglutide 2.4 mg, the GLP-1 receptor agonist sold as Ozempic for diabetes and Wegovy for obesity [3]. Novo Nordisk says that if cleared, it would be the first FDA-approved injectable combination of a GLP-1 receptor agonist and an amylin analog [3]. The company says the drug would be used along with a reduced-calorie diet and increased physical activity [3]. CagriSema is not approved in the U.S. or the European Union [3].
The filing rests mainly on REDEFINE 1, a 68-week phase 3 trial in 3,417 adults with obesity or overweight who did not have diabetes [3]. CagriSema produced average weight loss of 20.4%, from an average starting weight of 236 pounds, versus 3.0% from 235 pounds for placebo, counting all patients regardless of whether they stayed on treatment [3]. Counting only patients who stayed on treatment, weight loss averaged 22.7% versus 2.3% [3]. About 91.9% of people taking CagriSema lost at least 5% of body weight versus 31.5% on placebo, and 54% of those who had obesity at the start reached a BMI below 30 at week 68 versus 11.1% on placebo [3]. A December 2024 readout of the same trial reported 11.5% weight loss with cagrilintide alone and 14.9% with semaglutide alone [4]. A later report, in September 2025, described 11.8% weight reduction with CagriSema versus 2.3% for placebo in a phase 3 trial but did not identify the trial [4].
The second trial behind the filing, REDEFINE 2, tested CagriSema against placebo for 68 weeks in 1,206 adults with type 2 diabetes who had obesity or were overweight [3].
Gastrointestinal side effects were common in REDEFINE 1: 79.6% of people on CagriSema reported them versus 39.9% on placebo, including nausea in 55% versus 12.6%, constipation in 30.7% versus 11.6% and vomiting in 26.1% versus 4.1% [3]. Discontinuation because of adverse events was 5.9% with CagriSema versus 3.5% with placebo in REDEFINE 1, and 8.4% versus 3% in REDEFINE 2 [3]. Injection-site reactions were reported by 12% of patients in REDEFINE 1, rising to 17% among those taking cagrilintide alone and 2.6% among those taking semaglutide alone [4]. Novo Nordisk says the safety profile was comparable with the GLP-1 receptor agonist class [3].
"The FDA submission of CagriSema marks an important milestone and signals a new era in weight management," said Mike Doustdar, Novo Nordisk's president and CEO [3]. He also said CagriSema "has the potential to represent a meaningful step forward in the holistic treatment of obesity" [3].
BioSpace reported that analysts said CagriSema's weight-loss results looked comparable to Eli Lilly's tirzepatide, sold as Zepbound for obesity and Mounjaro for diabetes, which did not raise the same injection-site reactions [4]. Lilly said the same day that its experimental oral drug orforglipron maintained weight loss in patients who switched from Wegovy or Zepbound, and Lilly is awaiting an FDA decision on orforglipron in early 2026 [4].
Why it matters for patients
If approved, CagriSema would add a second mechanism, amylin, alongside the GLP-1 pathway that semaglutide and tirzepatide work on, giving patients and doctors another option in a category where response and tolerability vary [3][4]. It would be given once a week by injection [3].
The data so far cover 68 weeks and weight change. Whether the combination lowers rates of heart attacks, strokes or other complications has not been established; REDEFINE 3, a cardiovascular outcomes trial, is still running [3].
The FDA has not yet decided on the application, so the drug is not available now, and no price or insurance coverage details have been disclosed [3].
Gastrointestinal side effects affected most participants in REDEFINE 1, and 5.9% of people on the drug in that trial stopped because of side effects [3]. Injection-site reactions also occurred more often with the cagrilintide component than with semaglutide alone [4].
What happens next
FDA review of the application is expected in 2026 [3]. In its Feb. 3, 2026 financial report, Novo Nordisk said it looks forward to regulatory decisions for next-generation treatments including CagriSema in obesity, and said phase 3 trials of CagriSema in diabetes, REIMAGINE 2 and 3, had been completed [2]. REDEFINE 11, a longer phase 3 trial in people with a BMI of 30 or higher, is also underway [3].
Images from the sources
Sources
- https://www.pharmexec.com/view/novo-nordisk-submits-nda-fda-cagrisema
- https://www.sec.gov/Archives/edgar/data/353278/000035327826000006/caq42025.htm
- https://www.prnewswire.com/news-releases/novo-nordisk-files-for-fda-approval-of-cagrisema-the-first-once-weekly-combination-of-glp1-and-amylin-analogues-for-weight-management-302645862.html
- https://www.biospace.com/fda/novo-nordisk-files-combo-obesity-drug-cagrisema-for-fda-approval
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