Novo Nordisk plans higher-dose CagriSema trials after REDEFINE 4 miss

Novo Nordisk said on 23 February 2026 that it will test higher doses of its experimental obesity drug CagriSema and run a trial designed to measure the drug's "full weight-loss potential," after a head-to-head study missed its main goal against tirzepatide, the drug sold as Zepbound and Mounjaro ^[1].

REDEFINE 4 enrolled 809 people with obesity and at least one related health condition, with an average starting weight of 114.2 kg (about 252 pounds). The trial ran for 84 weeks, everyone knew which drug they were getting, and both drugs were given as once-weekly injections ^[1].

People who took CagriSema 2.4 mg/2.4 mg — a fixed-dose combination of cagrilintide and semaglutide, the molecule in Ozempic, Wegovy and Rybelsus — lost 23.0% of their body weight when everyone in the analysis adhered to treatment, compared with 25.5% for tirzepatide 15 mg. Counting everyone regardless of whether they stayed on treatment, the figures were 20.2% and 23.6% ^[1]. Those two pairs of numbers describe the same trial under different statistical assumptions, not conflicting results ^[2]. The trial did not meet its primary endpoint of showing CagriSema was at least as good as tirzepatide for weight loss ^[1].

Novo Nordisk's chief scientific officer, Martin Holst Lange, said the company was "pleased with the weight loss of 23%" and that cagrilintide "adds to the existing benefits of semaglutide" ^[1]. Shares of Novo Nordisk fell more than 12% in Copenhagen trading on the day of the announcement, while Eli Lilly, which makes tirzepatide, gained about 4% in United States pre-market trading ^[2].

Side effects in REDEFINE 4 were mostly gastrointestinal, and the vast majority were mild to moderate and eased over time, the company said ^[1]. In an earlier trial, REDEFINE 1, nausea affected 55% of CagriSema recipients, constipation 30.7% and vomiting 26.1%; 5.9% stopped treatment because of side effects, compared with 3.5% on placebo ^[2].

REDEFINE 1 enrolled 3,417 adults and ran for 68 weeks. Average weight loss was 22.7% versus 2.3% for placebo under one analysis, and 20.4% versus 3.0% under another. Semaglutide 2.4 mg alone produced 14.9% and cagrilintide 2.4 mg alone 11.5% ^[2]. Novo Nordisk submitted CagriSema for FDA approval in weight management in December 2025 based on REDEFINE 1 and REDEFINE 2, and says a decision is anticipated by late 2026 ^[1]. CagriSema is not approved for any use.

Novo Nordisk has also withdrawn a phase 2 study of alternative injection devices for CagriSema in type 2 diabetes, a move reported as unrelated to how well the drug works ^[2].

Why it matters for patients

Nothing changes right now for people taking Ozempic, Wegovy, Rybelsus, Zepbound, Mounjaro or other GLP-1 medicines, because CagriSema is not approved ^[1][2]. The FDA's decision on the weight-management application is expected to rest on the placebo-controlled REDEFINE 1 and REDEFINE 2 trials, not on the comparison with tirzepatide, so the head-to-head result has no direct bearing on that review — though it may matter for how doctors, insurers and pharmacy benefit managers rank the drug if it reaches the market ^[2].

At the doses tested, CagriSema did not match tirzepatide for weight loss over 84 weeks, and it is not yet known whether higher doses will close that gap or add gastrointestinal side effects; that data has not been reported ^[1]. Pricing, insurance coverage and a US launch date for CagriSema have not been disclosed ^[1][2].

What happens next

• Second half of 2026: Novo Nordisk plans to start a phase 3 trial of a higher-dose combination, cagrilintide 2.4 mg with semaglutide 7.2 mg, in adults with obesity ^[1].
• Late 2026: The company expects an FDA decision on CagriSema for weight management. As of July 2026, no target action date under the Prescription Drug User Fee Act had been publicly confirmed, the filing did not appear to carry priority review, and no advisory committee meeting had been scheduled ^[1][2].
• First half of 2027: Results from REDEFINE 11, an 80-week phase 3 trial of CagriSema 2.4/2.4 mg in 600 adults with obesity, with an 80-week extension phase studying maintenance of weight loss ^[1].