CagriSema in 2026: head-to-head results and a pending FDA decision

CagriSema, Novo Nordisk's once-weekly co-administration of the amylin analogue cagrilintide and the GLP-1 receptor agonist semaglutide, had a mixed 2026 in the clinic while its US application remained under FDA review ^1,2,3. CagriSema is investigational and is not approved in the US or EU ¹. This article summarizes the company-reported milestones; the earlier REDEFINE 1 and REDEFINE 2 results are covered in Amiravo's incretin pipeline overview.

December 2025: US submission

Novo Nordisk announced on 18 December 2025 that it had submitted a New Drug Application to FDA for CagriSema (cagrilintide 2.4 mg and semaglutide 2.4 mg) for weight reduction and long-term weight maintenance in adults with obesity, or overweight with at least one weight-related comorbidity ¹.

February 2026: REDEFINE 4 misses its primary endpoint

REDEFINE 4 was an 84-week, open-label phase 3 trial in 809 adults with obesity and comorbidities, comparing CagriSema 2.4 mg/2.4 mg with tirzepatide 15 mg ². Novo reported mean weight loss of 23.0% with CagriSema versus 25.5% with tirzepatide under the efficacy estimand, and 20.2% versus 23.6% under the treatment-regimen estimand ². The trial did not show non-inferiority of CagriSema to tirzepatide on weight loss ². The most common adverse events with CagriSema were gastrointestinal ².

May 2026: device plan

In first-quarter materials, Novo said it had stopped a co-formulation project that could have allowed a single-chamber device, and that CagriSema remains planned for a dual-chamber pen; its chief executive said there was no change to launch plans ⁴.

September 2026: REIMAGINE 5 and REDEFINE 9

On 21 September 2026, Novo reported two further phase 3 readouts ³:

• REIMAGINE 5, a 60-week trial in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both, compared CagriSema 1.0 mg/1.0 mg with tirzepatide 5 mg. Novo reported estimated mean weight loss of 12.4% versus 9.1% (efficacy estimand), meeting a superiority endpoint, and HbA1c reductions of 1.71% versus 1.67%, meeting non-inferiority ³. These are lower doses of both drugs than were compared in REDEFINE 4.
• REDEFINE 9, a 68-week placebo-controlled trial in adults with overweight or obesity, reported mean weight reduction of 21.0% with CagriSema 1.0 mg/1.0 mg versus 2.0% with placebo ³.

The release did not report participant numbers or adverse event rates for either trial ³.

Regulatory status

Novo states that an FDA decision on the weight-management application is expected in the fourth quarter of 2026 ³, and trade reporting cites a planned US launch in early 2027 if approved ⁴. As of this writing, FDA has not announced a decision. Separately, FDA states that cagrilintide cannot be used in compounding under federal law ⁵.

What this means for readers

• Head-to-head results depend heavily on the doses compared: REDEFINE 4 compared the highest doses, REIMAGINE 5 compared lower ones, and the two results are not contradictory.
• The September figures are company-reported and not yet peer-reviewed; trial sizes and full safety data were not disclosed.
• An FDA decision, whichever way it goes, would apply to the specific combination product and indication submitted, not to cagrilintide or semaglutide sold separately.
• See the cagrilintide and semaglutide entries for the published literature.