Novo Nordisk Files NDA for CagriSema, Novel GLP-1-amylin Combination for Chronic Weight Management

Novo Nordisk today announced submission to the FDA of a New Drug Application (NDA) seeking approval of once-weekly CagriSema (cagrilintide 2.4 mg/semaglutide 2.4 mg) for chronic weight management in adults with obesity or overweight and at least 1 weight-related comorbidity.¹

If approved, CagriSema would become the first fixed-dose injectable combination of a GLP-1 receptor agonist and an amylin analogue for weight management, according to the company.

CagriSema combines semaglutide, a GLP-1 receptor agonist with an established role in obesity treatment, with cagrilintide, a long-acting amylin analogue designed to target complementary obesity-related pathways. Novo Nordisk positioned the filing as part of its broader obesity pipeline and as a potential new option for long-term weight reduction when used alongside a reduced-calorie diet and increased physical activity.¹

“The FDA submission of CagriSema marks an important milestone and signals a new era in weight management, reinforcing Novo Nordisk's long-standing commitment to serving people living with obesity through innovation and science,” Mike Doustdar, president and CEO of Novo Nordisk, said in a statement. “Building on the well-established profile of semaglutide and combining it with a novel mechanism of action, CagriSema has the potential to represent a meaningful step forward in the holistic treatment of obesity.”¹

Biological Logic

The GLP-1 receptor agonist/long-acting amylin analogue combination makes biological sense because the 2 hormones regulate appetite and energy intake through complementary central and peripheral pathways.^2,3 GLP-1 receptor agonists enhance satiety and slow gastric emptying, while amylin analogues act on distinct hindbrain and hypothalamic circuits to promote meal-related satiety and suppress compensatory mechanisms that can limit the durability of weight loss with monotherapy.^2,3

Phase 3 Evidence: REDEFINE Trial Program

The NDA is supported primarily by results from the phase 3 REDEFINE clinical trial program, including REDEFINE 1 and REDEFINE 2. REDEFINE 1 was a 68-week, randomized, double-blind, placebo- and active-controlled trial that enrolled 3,417 adults with obesity (BMI 30 kg/m² or greater) or overweight (BMI 27 kg/m² or greater) with at least 1 obesity-related complication and without diabetes. Participants received once-weekly CagriSema, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo, all in combination with lifestyle intervention.¹

In REDEFINE 1, when evaluating the treatment effect regardless of whether participants stayed on treatment, adults treated with CagriSema achieved mean weight loss of 20.4% from an average baseline body weight of 236 lb at week 68, compared with 3.0% from a baseline of 235 lb in the placebo group, a statistically significant difference, according to Novo Nordisk. When assessing the treatment effect assuming all patients remained on therapy, mean weight loss reached 22.7% with CagriSema versus 2.3% with placebo. In addition, 91.9% of participants receiving CagriSema achieved at least 5% body weight reduction, compared with 31.5% in the placebo group, the company reported.

A supportive secondary analysis showed that approximately 54% of participants with obesity at baseline treated with CagriSema reached a BMI below 30 kg/m² at week 68, compared with 11.1% in the placebo group.

REDEFINE 2 was a 68-week, randomized, double-blind, placebo-controlled phase 3 trial in 1,206 adults with type 2 diabetes and either obesity or overweight. That study evaluated once-weekly CagriSema vs placebo, both as adjuncts to lifestyle intervention, and contributed additional efficacy and safety data to the NDA.¹

“This submission reflects the continued advancement of Novo Nordisk's obesity pipeline and our focus on translating scientific innovation into patient-relevant outcomes,” the company stated. “If approved, CagriSema would provide patients and healthcare professionals with an additional treatment option supported by results from the REDEFINE clinical program, including robust efficacy, high treatment completion rates, and a tolerability profile consistent with its underlying pharmacology.”¹

Safety and Tolerability

Across REDEFINE 1 and REDEFINE 2, safety findings aligned with the established profile of the GLP-1 receptor agonist class. Discontinuation rates due to adverse events remained low, at 5.9% with CagriSema versus 3.5% with placebo in REDEFINE 1, and 8.4% versus 3.0%, respectively, in REDEFINE 2, Novo stated.

In REDEFINE 1, adverse events occurred mainly in the gastrointestinal system and affected 79.6% of participants receiving CagriSema compared with 39.9% in the placebo group. Reported events included nausea (55% vs 12.6%), constipation (30.7% vs 11.6%), and vomiting (26.1% vs 4.1%).¹

Regulatory Outlook, Ongoing Research

Novo Nordisk expects the FDA to review the CagriSema application in 2026. The drug remains investigational and is not approved in the US or EU.

Beyond REDEFINE 1 and 2, the phase 3 REDEFINE program includes additional ongoing trials, such as REDEFINE 3, an event-driven cardiovascular outcomes study, and REDEFINE 11, a longer-duration phase 3 trial enrolling patients with BMI 30 kg/m² or greater. CagriSema is also being evaluated in the REIMAGINE program for adults with type 2 diabetes.

If approved, CagriSema would enter a rapidly evolving obesity treatment landscape, offering clinicians a once-weekly, fixed-dose combination that targets both GLP-1 and amylin pathways for long-term weight management.¹

References

1. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP‑1 and amylin analogues for weight management. News release. Novo Nordisk. December 18, 2025. Accessed December 18, 2025. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=916469

2. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740-756. doi:10.1016/j.cmet.2018.03.001

3. Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. 2015;67(3):564-600. doi:10.1124/pr.114.009233