Novo Nordisk's CagriSema misses main goal in head-to-head trial against tirzepatide

Novo Nordisk said on Feb. 23, 2026 that its experimental obesity drug CagriSema helped people lose less weight than tirzepatide 15 mg, the molecule sold as Zepbound, in an 84-week head-to-head phase 3 trial. The study missed its main goal, and the company's shares fell more than 15% ^[1][2].

What the trial found

The trial, called REDEFINE 4, enrolled 809 people with obesity and one or more other health conditions. Their average starting weight was 114.2 kg, about 252 pounds ^[1]. Participants received once-weekly injections of either CagriSema, a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, or tirzepatide 15 mg ^[1]. The trial was open-label, meaning participants and investigators knew which drug was given ^[1].

Novo Nordisk reported the results two ways. Counting everyone as if they had stayed on treatment as planned, an approach called the efficacy estimand, CagriSema produced 23.0% weight loss at 84 weeks versus 25.5% for tirzepatide ^[1]. Counting people regardless of whether they stayed on treatment, the treatment-regimen estimand, the figures were 20.2% and 23.6% ^[1]. Under either measure, the trial did not achieve its primary endpoint: showing that CagriSema was non-inferior, or at least as good, as tirzepatide ^[1].

BioPharma Dive reported the results as about 20% weight loss for CagriSema compared with 24% for Zepbound, which are the treatment-regimen numbers rounded ^[2].

Safety and reaction

Novo Nordisk said CagriSema "appeared to have a safe and well-tolerated profile." The most common side effects were gastrointestinal, the vast majority were mild to moderate, and they diminished over time, consistent with the GLP-1 receptor agonist class ^[1].

Semaglutide is the active ingredient in Ozempic, Wegovy and Rybelsus; tirzepatide is the active ingredient in Mounjaro and Zepbound.

Martin Holst Lange, Novo Nordisk's executive vice president for research and development, said the company was "pleased with the weight loss of 23% for CagriSema in this open-label trial" and that cagrilintide adds to the effects of semaglutide ^[1]. On a call with reporters, he also said that "from a strict label perspective, CagriSema will actually have a strong and very competitive weight loss label" ^[2].

Analysts were less positive. William Blair analyst Andy Hsieh called the finding a "worst case scenario" ^[2]. Jefferies analyst Michael Leuchten wrote that "it is difficult to command a premium positioning for the drug" and that his team struggled to understand what role CagriSema will play going forward ^[2]. Novo Nordisk shares have fallen more than 50% over the past year and are 72% below record highs reached in mid-2024 ^[2]. BioPharma Dive also reported that earlier in February, Novo predicted sales of its obesity drugs would shrink in 2026 amid pricing pressure and competition for Wegovy ^[2].

Why it matters for patients

CagriSema is not approved for weight management in the United States. Novo Nordisk submitted it to the FDA in December 2025 based on two other trials, REDEFINE 1 and REDEFINE 2, and an FDA decision is anticipated by late 2026 ^[1]. BioPharma Dive likewise reported that a decision is expected later this year ^[2]. This result does not change any medicine that is available now.

Head-to-head trials that directly compare two obesity drugs are uncommon, so REDEFINE 4 offers a direct comparison between CagriSema and tirzepatide 15 mg rather than comparisons across separate studies ^[1][2]. The reported figures are group averages; the sources do not say how many people in each group reached a particular amount of weight loss. Because the trial was open-label, everyone involved knew which treatment was given ^[1].

Analysts quoted by BioPharma Dive said the data raise questions about how CagriSema would be positioned if approved, with Zepbound and similar drugs expected to keep market leadership in the US ^[2].

What happens next

Novo Nordisk held an investor conference call on Feb. 23, 2026 ^[1]. The company expects an FDA decision on CagriSema by late 2026 ^[1]. Results from REDEFINE 11, an 80-week phase 3 trial of CagriSema 2.4 mg/2.4 mg in 600 adults with obesity, are expected in the first half of 2027 ^[1]. A separate phase 3 trial of a higher dose, CagriSema 2.4 mg/7.2 mg, is planned to begin in the second half of 2026 ^[1].