CagriSema meets primary endpoint in REDEFINE 9 with 21.0% weight loss versus 2.0% on placebo

Novo Nordisk said on September 21, 2026 that its Phase 3 REDEFINE 9 trial met its primary endpoint, with once-weekly CagriSema at a 1.0 mg/1.0 mg dose producing 21.0% weight loss at week 68 compared with 2.0% for placebo in adults living with overweight or obesity ^[1]. The company called the result statistically significant and clinically meaningful, and said the safety profile was consistent with previous studies ^[1].

CagriSema is an investigational fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, the GLP-1 receptor agonist sold as Ozempic, Wegovy and Rybelsus ^[1]. REDEFINE 9 was a 68-week trial in about 300 adults with overweight or obesity that tested two lower doses — 1.7 mg/1.7 mg and 1.0 mg/1.0 mg — against placebo, on top of a reduced-calorie diet and increased physical activity ^[2]. The trial's primary endpoints were the relative change in body weight and the share of participants losing at least 5% of body weight from baseline to week 68 ^[1].

Beyond weight, Novo said CagriSema beat placebo on prespecified supportive endpoints including systolic blood pressure, waist-to-height ratio and fasting lipid profile ^[1]. The 21.0% figure is based on what Novo calls the efficacy estimand, which estimates the effect if participants had stayed on treatment ^[1]. Results for the 1.7 mg/1.7 mg arm, the proportion of people reaching the 5% threshold, and detailed side-effect and discontinuation rates were not included in the announcement.

A low dose, and a separate diabetes comparison

The same day, Novo released topline data from REIMAGINE 5, a trial in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both ^[1]. There, CagriSema 1.0 mg/1.0 mg produced 12.4% weight loss at week 60 versus 9.1% for tirzepatide 5 mg — the low dose of the molecule sold as Mounjaro and Zepbound — and a non-inferior HbA1c reduction of 1.71% versus 1.67% ^[1].

"With only 1.0 mg/1.0 mg, CagriSema shows superior weight loss versus tirzepatide 5 mg as well as strong results across obesity and type 2 diabetes," said Martin Holst Lange, Novo's executive vice president for research and development and chief scientific officer ^[1]. He added that CagriSema "remains investigational" ^[1].

The emphasis on low doses follows a disappointing head-to-head result earlier in 2026. In February, Novo reported that REDEFINE 4, an open-label 84-week trial in 809 people with obesity and at least one other condition, failed its primary endpoint of showing that CagriSema 2.4 mg/2.4 mg was non-inferior to tirzepatide 15 mg on weight loss ^[2]. CagriSema produced 23.0% weight loss versus 25.5% for tirzepatide under the efficacy estimand, and 20.2% versus 23.6% when measured regardless of whether people stayed on treatment ^[2]. Mean baseline body weight in that trial was 114.2 kg ^[2].

The two trials are not directly comparable: REDEFINE 4 ran 84 weeks against an active comparator at its top dose, while REDEFINE 9 ran 68 weeks against placebo in a much smaller group ^[2].

Why it matters for patients

Most weight-loss drugs are studied at their highest tolerated dose, but many people never get there — because of side effects, cost, supply or personal preference. Novo argued that treatment decisions are individualized and that "not all patients receive or remain on the highest available dose of current therapies," framing the REDEFINE 9 and REIMAGINE 5 data as evidence about dose flexibility ^[1].

If that holds up in review, it would mean a lower-dose option that still delivered roughly 21% average weight loss in a placebo-controlled trial ^[1]. Averages, though, hide wide individual variation, and topline company statements are not the same as peer-reviewed data. The full results have not been published or presented in detail, and no date for a scientific presentation has been disclosed.

CagriSema is not approved anywhere. Nothing in these results changes what is available at a US pharmacy today.

What happens next

Novo filed a New Drug Application with the US Food and Drug Administration in December 2025 for CagriSema for weight management, based on the pivotal REDEFINE 1 and REDEFINE 2 trials, and a decision is expected in the fourth quarter of 2026 ^[1][2]. Those filings cover the 2.4 mg/2.4 mg dose ^[2].

Novo also said the REDEFINE 11 trial of CagriSema 2.4 mg/2.4 mg should report in the first half of 2027, and that a Phase 3 trial of a higher-dose version, 2.4 mg/7.2 mg, was planned to start in the second half of 2026 ^[2].