CagriSema weight-loss drug trials

On September 21, 2026, Novo Nordisk announced that its investigational combination drug CagriSema drove 21.0% weight loss in adults with obesity over 68 weeks, while simultaneously outperforming Eli Lilly's tirzepatide in a separate head-to-head trial for type 2 diabetes. The topline results from the Phase 3 REDEFINE 9 and REIMAGINE 5 trials mark a critical milestone for the Danish pharmaceutical company as it prepares to defend its market share against Lilly's highly successful Zepbound and Mounjaro franchises.[1][3][4]

The REIMAGINE 5 trial directly compared a 1.0 milligram dose of CagriSema against a 5.0 milligram dose of tirzepatide in patients with type 2 diabetes whose blood sugar was inadequately controlled on metformin or SGLT2 inhibitors. Over 60 weeks, patients receiving CagriSema achieved an estimated average weight loss of 12.4%, clearing the superiority threshold against the 9.1% weight loss recorded in the tirzepatide cohort.[4][5]

Beyond weight reduction, CagriSema also met its glycemic targets in the diabetes study. The combination therapy reduced HbA1c levels by 1.71 percentage points, confirming non-inferiority to the 1.67 percentage point reduction achieved by tirzepatide. "The results from CagriSema are very encouraging, demonstrating the strong potency of the combination of semaglutide and cagrilintide," said Martin Holst Lange, Novo Nordisk's chief scientific officer. "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."[3][5]

In the parallel REDEFINE 9 obesity trial, which evaluated the drug as an adjunct to a reduced-calorie diet and increased physical activity, the results were even more pronounced. Adults living with overweight or obesity who received the 1.0 milligram dose of CagriSema lost 21.0% of their body weight over 68 weeks, compared to just 2.0% for those on a placebo.[4]

The REDEFINE 9 data also showed that CagriSema delivered greater improvements across several prespecified cardiometabolic markers. Patients on the active drug saw superior reductions in systolic blood pressure, waist-to-height ratio, and fasting lipid profiles compared to the placebo group. Novo Nordisk reported that the drug was well tolerated across both trials, with a safety profile consistent with previous incretin-based therapies.[4][5]

CagriSema operates through a dual mechanism, combining two different long-acting receptor agonists into a single weekly subcutaneous injection. It pairs semaglutide—the GLP-1 receptor agonist that powers Wegovy and Ozempic—with cagrilintide, an investigational compound that mimics the pancreatic hormone amylin. This combination is designed to suppress appetite and delay gastric emptying through multiple complementary biological pathways.[2]

The head-to-head victory in REIMAGINE 5 is particularly significant for Novo Nordisk's strategic positioning. Eli Lilly's tirzepatide, a dual GLP-1 and GIP receptor agonist, had previously set a high bar in the incretin market, often showing an edge over semaglutide alone in indirect comparisons. By demonstrating superiority over a 5.0 milligram dose of tirzepatide, Novo Nordisk has provided clinical evidence that adding amylin agonism can push efficacy beyond current dual-agonist standards.[2][3]

However, the REIMAGINE 5 trial design carries a specific limitation: it evaluated CagriSema against the lowest therapeutic dose of tirzepatide (5.0 milligrams), rather than the 10.0 or 15.0 milligram doses frequently used in clinical practice for maximum weight loss. While the 1.0 milligram dose of CagriSema is also on the lower end of its testing range, the lack of a high-dose comparison leaves some questions open regarding how the two drugs match up at their maximum tolerated strengths.[2][5]

AI

Novo Nordisk had already submitted a New Drug Application for CagriSema for weight management to the U.S. Food and Drug Administration in December 2025, based on earlier data from the REDEFINE clinical program. The company expects a regulatory decision in the fourth quarter of 2026. If approved, CagriSema will enter a rapidly expanding market where demand for highly effective anti-obesity medications continues to outpace manufacturing capacity.[4]

The latest data release aligns with Novo Nordisk's broader strategy to transition its portfolio ahead of Wegovy's anticipated patent expirations in the early 2030s. At a recent investor briefing in London, the company outlined plans to reach more than 150 billion Danish kroner ($23.05 billion) in pipeline drug sales by 2035, leaning heavily on next-generation combinations like CagriSema to sustain its growth trajectory.[3][4]