CagriSema Demonstrates Weight Loss, Fails to Achieve Primary Endpoint Compared to Tirzepatide

On February 23, 2026, Novo Nordisk announced that, despite demonstrating substantial weight loss after 84 weeks of treatment, CagriSema 2.4/2.4 mg failed to meet its primary endpoint of noninferiority compared to tirzepatide 15 mg.1

“We are pleased with the weight loss of 23% for CagriSema in this open-label trial,” Martin Holst Lange, MD, executive vice president, R&D and chief scientific officer at Novo Nordisk, said in a statement. “CagriSema has the potential to be the first GLP-1/amylin-combination product to reach the market for people living with obesity, documenting that cagrilintide adds to the existing benefits of semaglutide and offers clinically meaningful additive weight loss effects superior to what has been observed with GLP-1 biology alone.”1

CagriSema is a fixed-dose combination of cagrilintide 2.4, a long-acting amylin analogue, and semaglutide 2.4 mg. The drug induces weight loss by reducing hunger and increasing feelings of fullness, helping people eat less and reduce their calorie intake. CagriSema is currently under investigation for overweight and obesity in the REDEFINE program and as a treatment for adults with type 2 diabetes (T2D) in the REIMAGINE program.1

REDEFINE is a phase 3 clinical development program comprised of 2 pivotal phase 3 trials including roughly 4600 adults with overweight or obesity. The program includes the following:

• REDEFINE 1, an efficacy trial comparing CagriSema to placebo in patients with overweight or obesity without T2D, lasting 68 weeks and enrolling 3417 patients
• REDEFINE 2, an efficacy trial comparing CagriSema to placebo in patients with T2D and either obesity or overweight, lasting 68 weeks and enrolling 1206 patients
• REDEFINE 3, an event-driven cardiovascular outcomes trial of CagriSema versus placebo in patients with established cardiovascular disease with or without T2D, enrolling 7000 patients
• REDEFINE 8, an efficacy trial comparing CagriSema to placebo in patients with obesity, lasting 104-weeks and enrolling 400 patients. This trial includes a 52-week extension phase investigating weight loss maintenance
• REDEFINE 9, an efficacy trial comparing CagriSema to placebo in adults with obesity or overweight, lasting 68 weeks and enrolling 300 patients
• REDEFINE 11, an efficacy trial of CagriSema compared to placebo in patients with obesity, lasting 80 weeks and enrolling 600 patients. This trial includes an 80-week extension phase investigating weight loss maintenance.1,2

REDEFINE 4 was an 84-week open-label trial investigating CagriSema compared to tirzepatide, both of which were administered once weekly and subcutaneously. A total of 809 patients with obesity and ≥1 comorbidity, with a mean baseline body weight of 114.2 kg (251.77 lb), were enrolled in the trial.1

Investigators found that, if all patients adhered to treatment, those receiving CagriSema 2.4 mg/2.4 mg saw a 23% weight loss after 84 weeks compared to 25.5% with tirzepatide. After applying the treatment regimen estimand, patients receiving CagrimSema saw weight loss of 20.2%, while tirzepatide recipients saw 23.6% weight loss.1

Despite missing the primary endpoint of noninferiority, CagriSema did display a safe and well-tolerated profile. The most common adverse events were gastrointestinal, with the vast majority labelled as mild to moderate and diminishing over time.1

“Based on the learnings from completed studies we look forward to the REDEFINE 11 readout, and the initiation of the higher-dose CagriSema trial, which are both designed to assess the full weight-loss potential of CagriSema,” Lange said. “The results in the REDEFINE program reinforce our commitment to transforming obesity care, through novel products such as CagriSema and zenagamtide with the potential to offer even greater health benefits for patients living with obesity.”1

CagriSema has been submitted to the US Food and Drug Administration for weight management in December 2025, based on the REDEFINE 1 and REDEFINE 2 pivotal trials. According to the press release, Novo Nordisk anticipates a decision by late 2026.1

References

1. Novo Nordisk. Novo Nordisk A/S: CagriSema demonstrated 23% weight loss in an open-label head-to-head REDEFINE 4 trial in people with obesity, the primary endpoint was not achieved. February 23, 2026. Accessed February 23, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916501

2. Hales CM. Expanding the Treat-to-Target Toolbox for Obesity and Diabetes Care. N Engl J Med. 2025;393(7):712-714. doi:10.1056/NEJMe2509700