CagriSema is under FDA review, with a decision anticipated by late 2026
CagriSema, Novo Nordisk’s once-weekly fixed-dose combination of the GLP-1 analogue semaglutide and the amylin analogue cagrilintide, is under review at the US Food and Drug Administration, and the company has said an FDA decision is anticipated by late 2026. The application for weight management was submitted in December 2025 on the basis of the REDEFINE 1 and REDEFINE 2 pivotal trials. CagriSema is investigational: it is not approved by the FDA, and a filing under review is not an approval.
What CagriSema is
CagriSema combines two peptides in a single once-weekly subcutaneous injection: semaglutide 2.4 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, and cagrilintide 2.4 mg, a long-acting analogue of the pancreatic hormone amylin. Novo Nordisk describes it as a fixed-dose combination in which the two molecules act through different signalling routes — the stated rationale for pairing them rather than using either alone. Background on each half of the combination is available on the VialHelp library pages for cagrilintide and semaglutide.
Where the FDA filing stands
According to Novo Nordisk’s own company announcement, CagriSema for weight management was submitted to the FDA in December 2025, based on the REDEFINE 1 and REDEFINE 2 pivotal phase 3 trials, and “an FDA decision is anticipated by late 2026.” The company has not publicly confirmed a PDUFA goal date. As with any application under review, the possible outcomes include approval, a complete response, or a request for additional information; nothing about the timeline is guaranteed.
What the pivotal trials measured
The REDEFINE programme is Novo Nordisk’s phase 3 development programme for CagriSema in obesity. The two trials underpinning the filing were:
- REDEFINE 1 — a 68-week efficacy and safety trial in 3,417 adults with obesity, or overweight with one or more comorbidities and without type 2 diabetes, comparing CagriSema 2.4 mg/2.4 mg with cagrilintide alone, semaglutide alone and placebo.
- REDEFINE 2 — a 68-week efficacy and safety trial in 1,206 adults with type 2 diabetes and either obesity or overweight, comparing CagriSema with placebo.
Several further trials are running or planned around them, including REDEFINE 3, an event-driven cardiovascular outcomes trial in 7,000 adults with established cardiovascular disease, and REDEFINE 8, 9 and 11, which look at body composition, lower dose strengths and maintenance of weight loss respectively.
The head-to-head trial that missed its primary endpoint
On 23 February 2026 Novo Nordisk released headline results from REDEFINE 4, an 84-week open-label trial that compared CagriSema 2.4 mg/2.4 mg directly with tirzepatide 15 mg in 809 randomised adults with obesity and one or more comorbidities, mean baseline body weight 114.2 kg. Both were given once weekly by subcutaneous injection, and all investigators and participants knew which drug was being administered.
The company reported that, under the efficacy estimand (the effect if everyone had adhered to treatment), CagriSema produced 23.0% weight loss at 84 weeks versus 25.5% with tirzepatide; under the treatment-regimen estimand (regardless of adherence), the figures were 20.2% versus 23.6%. On that basis, Novo Nordisk stated that the trial did not achieve its primary endpoint of demonstrating non-inferiority on weight loss for CagriSema compared with tirzepatide at 84 weeks. Missing a non-inferiority endpoint is a specific statistical result, not a verdict on the compound.
Novo Nordisk also reported that CagriSema “appeared to have a safe and well-tolerated profile” in the trial, with the most common adverse events being gastrointestinal, mostly mild to moderate, diminishing over time and consistent with the GLP-1 receptor agonist class. These are company-reported headline figures; full methods and peer-reviewed data are where such results are normally scrutinised. Notably, REDEFINE 4 was not part of the filing package — the FDA submission rests on REDEFINE 1 and REDEFINE 2. For context on the comparator, see the VialHelp page for tirzepatide.
What comes next
Novo Nordisk has said the REDEFINE 11 phase 3 trial, designed to explore the full weight-loss potential of CagriSema 2.4 mg/2.4 mg, is expected to report during the first half of 2027, and that a phase 3 trial of a higher-dose CagriSema 2.4 mg/7.2 mg was planned to begin in the second half of 2026. Alongside the multi-receptor agonists now in late-stage testing — see our report on retatrutide’s TRIUMPH-2 and TRIUMPH-3 topline results — combination and multi-target peptide designs are where much of the current obesity pipeline sits.
Related on VialHelp
- Cagrilintide — compound background and references
- Semaglutide — compound background and references
- 503A vs 503B compounding, and where GLP-1s stand
- More VialHelp News
