CagriSema Achieves Superior HbA1c Control and Weight Loss in REIMAGINE 2 Trial

Novo Nordisk A/S, the Danish pharmaceutical company, has recently released headline results from its REIMAGINE 2 clinical trial, demonstrating that CagriSema outperforms semaglutide across multiple clinical endpoints. The fixed-dose combination therapy showed remarkable improvements in both HbA1c reduction and weight management in adults with type 2 diabetes over a 68-week study period.

Dual-Action Mechanism Driving Enhanced Results

CagriSema represents a novel therapeutic approach by combining two active compounds: cagrilintide, a long-acting amylin receptor agonist, and semaglutide, a long-acting GLP-1 receptor agonist. This dual-mechanism design targets multiple pathways involved in glucose regulation and weight management, allowing the combination to achieve superior outcomes compared to each component used individually. By leveraging both amylin and GLP-1 signaling pathways, the therapy addresses the complex pathophysiology of type 2 diabetes more comprehensively than single-agent therapies.

Superior HbA1c Control and Weight Reduction

In the 68-week efficacy and safety trial, CagriSema demonstrated a remarkable HbA1c reduction of 1.91 percentage points, representing substantial improvement in blood glucose control. The therapy also achieved an average weight loss of 14.2%, substantially exceeding what was observed with semaglutide monotherapy. Importantly, these therapeutic advantages were consistent across all tested dose levels, establishing the superiority of the combination approach versus individual components on both primary endpoints. Such dual improvements in HbA1c metrics and weight loss are particularly significant for patients requiring comprehensive metabolic management.

Favorable Safety Profile Supports Clinical Potential

The clinical data revealed that CagriSema maintains a safe and well-tolerated safety profile that aligns with established tolerability patterns of incretin-based and amylin-based therapies. No unexpected safety concerns emerged during the trial, supporting the potential for this novel combination as a treatment option for adults with type 2 diabetes who prioritize both glucose control and weight reduction. The consistency of the safety profile across different dose levels further reinforces the clinical viability of this therapeutic approach.

Regulatory Path and Market Development

Building on positive results from the REIMAGINE 1 trial and the REDEFINE 3 obesity program, Novo Nordisk plans to engage with regulatory authorities to establish the development pathway for CagriSema in type 2 diabetes. The company separately submitted CagriSema for weight management indication to the US FDA in December 2025, based on data from the REDEFINE 1 and REDEFINE 2 pivotal studies. Detailed findings from REIMAGINE 2 are expected to be presented at a major scientific conference in 2026.

Martin Holst Lange, Executive Vice President and Chief Scientific Officer at Novo Nordisk, commented on the significance of these results: “The combination of semaglutide and cagrilintide reveals superior outcomes in both glucose control and weight reduction that exceed what either therapy achieves alone. These results reinforce our conviction that CagriSema could represent the first amylin-based combination therapy and provide a meaningful treatment option for individuals managing type 2 diabetes with an emphasis on sustained weight loss.” The positive trial outcomes underscore CagriSema’s potential to redefine treatment standards in managing the metabolic complexity of type 2 diabetes, particularly for patients seeking comprehensive HbA1c improvement alongside significant weight reduction.