Novo’s CagriSema Tops Tirzepatide on Weight Loss in Phase 3 Trial

Novo Nordisk on 21 september 2026 reported topline phase 3 results showing that once-weekly CagriSema, its investigational fixed-dose combination of cagrilintide and semaglutide, delivered superior weight loss versus tirzepatide 5 mg in adults with type 2 diabetes and a 21.0% weight reduction versus placebo in adults living with overweight or obesity.

The Bagsværd, Denmark-based company announced the results from the REIMAGINE 5 and REDEFINE 9 trials in a company announcement, describing CagriSema as its next innovation in weight management and type 2 diabetes. The findings were highlighted at Novo’s Capital Markets Day investor briefing in London the same day.

REIMAGINE 5 and REDEFINE 9 Results

REIMAGINE 5 was a phase 3 trial investigating once-weekly CagriSema 1.0 mg/1.0 mg compared with tirzepatide 5 mg in participants with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both. The dual primary endpoints were change in HbA1c and relative change in body weight from baseline to week 60.

According to the company, CagriSema 1.0 mg/1.0 mg was superior to tirzepatide 5 mg for weight loss, achieving an estimated average weight loss of 12.4% compared with 9.1%. CagriSema also confirmed non-inferior reduction in HbA1c, at 1.71% versus 1.67% with tirzepatide.

REDEFINE 9 was a phase 3 trial investigating once-weekly CagriSema 1.7 mg/1.7 mg and CagriSema 1.0 mg/1.0 mg compared with placebo, as an adjunct to a reduced-calorie diet and increased physical activity, in participants living with overweight or obesity. The primary endpoints were relative change in body weight and the proportion of participants achieving at least 5% body-weight reduction from baseline to week 68.

Novo reported that CagriSema 1.0 mg/1.0 mg provided a weight reduction of 21.0% versus 2.0% for placebo, with the primary superiority endpoint met. CagriSema also showed greater improvements than placebo across prespecified supportive endpoints, including systolic blood pressure, waist-to-height ratio and fasting lipid profile. The reported efficacy figures in both trials were based on the efficacy estimand.

In both trials, CagriSema was well tolerated overall, with a safety profile consistent with previous studies, the company said.

“The results from CagriSema are very encouraging, demonstrating the strong potency of the combination of semaglutide and cagrilintide. 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, executive vice president, Research & Development and chief scientific officer at Novo. He added that CagriSema remains investigational, but that the findings strengthen the company’s confidence in its potential, add to the growing evidence for amylin biology and reinforce its ambition to advance the next generation of treatments for obesity and type 2 diabetes.

The company said treatment decisions in obesity and type 2 diabetes are often individualised, and not all patients receive or remain on the highest available dose of current therapies. It said the data provide evidence of the potential of CagriSema 1.0 mg/1.0 mg and expand understanding of how efficacy, tolerability and dose flexibility may support individualised care.

Also during Capital Markets Day, Novo presented data on painful diabetic neuropathy in type 2 diabetes for the first time, characterizing the results as promising. The company said more details will be presented at a later time.

Regulatory Status and Capital Markets Day

Once-weekly subcutaneous CagriSema is being investigated by Novo as a treatment for adults with overweight or obesity in the REDEFINE programme and as a treatment for adults with type 2 diabetes in the REIMAGINE programme. CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist.

Novo filed a New Drug Application with the U.S. Food and Drug Administration in december 2025 for CagriSema for weight management. The company said a decision is expected in the fourth quarter of 2026.

The Capital Markets Day event ran from 09:00 to 15:30 BST (10:00 to 16:30 CET) in London. The programme featured presentations from Executive Management and other members of senior management on the company’s strategy, R&D pipeline, business operations and performance, and included plenary presentations and Q&A sessions. According to the event page, all sessions were broadcast live via webcast and made available on demand.

President and CEO Maziar Mike Doustdar opened the event with a corporate strategy session. Lange presented an R&D and Portfolio Strategy session alongside Mishal Patel, GVP AI & Digital Innovation, and joined Hong Chow, EVP Product & Portfolio Strategy, for dedicated obesity and diabetes sessions. CFO Karsten Munk Knudsen presented the Financials session, and Doustdar delivered closing remarks.