Novo sets up higher-dose CagriSema and a full-potential trial

Novo Nordisk announced on February 23, 2026, that it is launching new trials to test whether higher doses of its experimental obesity drug CagriSema can match or beat tirzepatide, after a head-to-head study came up short at the currently marketed dose ^[1].

The trial, called REDEFINE 4, compared CagriSema 2.4 mg/2.4 mg against tirzepatide 15 mg (the active ingredient in Zepbound and Mounjaro) in 809 adults with obesity and at least one weight-related health condition over 84 weeks ^[1]. Using the measure that assumes everyone stayed on treatment as prescribed, CagriSema produced 23.0% weight loss compared with 25.5% for tirzepatide ^[1]. Using a second measure that accounts for people who stopped or reduced treatment, the gap was similar: 20.2% versus 23.6% ^[1]. Either way, CagriSema did not meet its goal of proving it works at least as well as tirzepatide, the trial's main target ^[1]. Novo said the most common side effects were gastrointestinal, mostly mild to moderate, and consistent with this class of drugs ^[1].

In response, Novo Nordisk is setting up two paths to test whether a higher dose of CagriSema could close the gap. One is REDEFINE 11, a trial of the standard 2.4 mg/2.4 mg dose designed to explore the drug's "full weight-loss potential," with results expected in the first half of 2027 ^[1]. The other is a new trial combining 2.4 mg of semaglutide with a much higher 7.2 mg dose of cagrilintide, set to begin in the second half of 2026 ^[1]. Martin Holst Lange, Novo's chief scientific officer, said the company is "pleased with the weight loss of 23% for CagriSema" and still sees it as a potential first-to-market GLP-1/amylin combination ^[1].

Separately, Novo Nordisk withdrew a phase 2 study of alternative injection devices for CagriSema in people with type 2 diabetes, an action reported in July 2026 ^[2]. That withdrawal is not tied to the REDEFINE 4 efficacy results and appears to reflect adjustments to how the company plans to deliver the drug rather than a change in the medicine itself ^[2].

CagriSema, a combination of the amylin analogue cagrilintide and semaglutide (the same GLP-1 molecule in Ozempic and Wegovy), was submitted to the FDA in December 2025 for weight management based on two earlier trials, REDEFINE 1 and REDEFINE 2, which compared the drug to placebo rather than to tirzepatide ^[1][2]. A decision from the FDA is expected by late 2026 ^[1]. The REDEFINE 4 results do not directly affect that FDA review, since regulators judge the drug against placebo, not against a competing medicine ^[2].

Why it matters for patients

For people currently weighing CagriSema against tirzepatide-based drugs like Zepbound, the REDEFINE 4 results suggest tirzepatide produced somewhat greater weight loss in this specific 84-week comparison, though both drugs showed substantial effects ^[1]. The new higher-dose trials mean it will take longer, until 2027, to know whether an adjusted CagriSema regimen can close that gap ^[1]. In the meantime, CagriSema is not yet approved in the United States, and its FDA decision, expected by late 2026, will be based on comparisons to placebo, not to tirzepatide ^[1][2]. Anyone considering CagriSema once it becomes available may want to know that the dose reviewed by the FDA is not necessarily the final word on how well the drug can perform, since Novo itself is testing whether a stronger version works better.

What happens next

An FDA decision on CagriSema for weight management is anticipated by late 2026 ^[1][2]. The new higher-dose CagriSema trial, combining 2.4 mg semaglutide with 7.2 mg cagrilintide, is set to begin in the second half of 2026 ^[1]. REDEFINE 11, testing the current 2.4 mg/2.4 mg dose for its full weight-loss potential, is expected to report results in the first half of 2027 ^[1].