CagriSema phase 3 trial shows 22.7% weight loss, below Novo Nordisk's 25% target
CagriSema, a semaglutide-plus-cagrilintide shot, hit 22.7% weight loss in its first phase 3 trial, under Novo Nordisk's 25% internal target, and is now under FDA review.
Novo Nordisk's experimental obesity drug CagriSema produced an average 20.4% weight loss at 68 weeks in the REDEFINE 1 phase 3 trial, or 22.7% when all participants were counted as staying on treatment [1][2]. That came in below the 25% weight-loss target Novo Nordisk had set internally for the study [1].
CagriSema is a once-weekly injection that combines two peptides in one dose: cagrilintide 2.4 mg, a long-acting amylin analog, and semaglutide 2.4 mg, the same molecule sold as Ozempic, Wegovy and Rybelsus [2]. It is not approved in the United States or the European Union [2]. The REDEFINE 1 and REDEFINE 2 results were presented at the American Diabetes Association meeting in June 2025 and published in the New England Journal of Medicine [1][2].
REDEFINE 1 enrolled adults with obesity (BMI of 30 or higher) or overweight (BMI of 27 or higher) with at least one weight-related condition, and no type 2 diabetes [2]. Novo Nordisk reports enrollment of 3,417 people, randomized to CagriSema, semaglutide alone, cagrilintide alone or placebo for 68 weeks, alongside diet and exercise [2]. One guide to the drug describes the trial as enrolling about 3,400 adults [1].
The results were reported two ways. Counting everyone assigned to the drug whether or not they stayed on it, CagriSema produced 20.4% weight loss versus 3.0% for placebo [2]. Assuming all patients stayed on treatment, the figures were 22.7% versus 2.3% [2]. Average starting weight was 236 pounds in the CagriSema group and 235 pounds in the placebo group [2]. Semaglutide alone produced 14.9% weight loss and cagrilintide alone 11.5% [1].
Other REDEFINE 1 numbers: 91.9% of CagriSema participants lost at least 5% of body weight, against 31.5% on placebo [2]. About 54% of those taking the drug moved below the BMI 30 threshold used to define obesity, against 11.1% on placebo [2]. And 40.4% of participants lost 25% or more of their starting weight [1].
In REDEFINE 2, which enrolled 1,206 adults with type 2 diabetes and obesity or overweight, CagriSema produced 13.7% average weight loss versus 3.4% for placebo, rising to 15.7% when all patients were assumed to stay on treatment [1][2].
One likely reason cited for the shortfall against the 25% target: only about half of REDEFINE 1 participants reached the highest dose during the trial window [1]. The maintenance dose was 2.4 mg of each peptide, reached after about 16 weeks of step-ups, and a later trial is testing a slower schedule [1].
Side effects tracked the GLP-1 class. In REDEFINE 1, gastrointestinal adverse events were reported by 79.6% of people on CagriSema versus 39.9% on placebo, including nausea (55% vs 12.6%), constipation (30.7% vs 11.6%) and vomiting (26.1% vs 4.1%) [2]. 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 [2].
Why it matters for patients
Nothing here can be prescribed yet. CagriSema remains investigational [2], and Novo Nordisk has not announced pricing [1]. One clinical guide says products advertised for sale as CagriSema are unregulated [1].
For people who have plateaued on semaglutide, the REDEFINE 1 comparison is the relevant one: adding cagrilintide moved average weight loss from 14.9% to 20.4% over 68 weeks [1]. The comparison with tirzepatide (sold as Zepbound for weight loss and Mounjaro for diabetes) is not settled. Tirzepatide produced up to 21% weight loss over 72 weeks in its SURMOUNT trials, and a direct head-to-head trial is running [1]. Retatrutide, an Eli Lilly candidate, showed about 24% weight loss at 48 weeks in phase 2, but no direct comparisons exist [1].
Gastrointestinal side effects were common in both CagriSema trials, and a minority of participants stopped treatment because of them [2].
What happens next
Novo Nordisk said on Dec. 18, 2025 that it submitted a New Drug Application to the FDA for CagriSema, and that the agency is expected to review it in 2026 [2]. A separate account of the drug's status says a filing was expected in early 2026, with a standard 10-to-12-month review and a possible U.S. launch in late 2026 [1]. The two timelines differ on when the application went in, and no decision date has been announced.
Several trials are ongoing: REDEFINE 3, a cardiovascular outcomes study; REDEFINE 11, a longer study in people with BMI of 30 or higher; and the head-to-head study against tirzepatide [1][2]. No specific dates have been given for those readouts beyond 2026 and 2027 [1].
Sources
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