CagriSema Demonstrates Superior HbA1c Reduction in REIMAGINE 2 Trial Success

Novo Nordisk A/S announced promising results from the REIMAGINE 2 clinical trial, where CagriSema outperformed semaglutide in controlling blood sugar levels among type 2 diabetes patients. The dual-acting therapy achieved a 1.91%-point reduction in HbA1c alongside 14.2% body weight reduction over the 68-week trial period, establishing superiority on both efficacy measures compared to individual components.

Combination Therapy Mechanism Delivers Enhanced Outcomes

CagriSema represents an innovative fixed-dose combination pairing a long-acting amylin receptor agonist (cagrilintide) with a long-acting GLP-1 receptor agonist (semaglutide). This synergistic approach addresses multiple metabolic pathways simultaneously. The trial data reveals that this combination strategy achieves greater HbA1c control than either agent administered separately, marking a potential paradigm shift for treatment-resistant hyperglycemia.

The amylin and GLP-1 dual mechanism targets both insulin secretion and glucagon suppression, addressing complementary aspects of glucose homeostasis that neither agent alone can fully optimize.

Clinical Efficacy Surpasses Single-Agent Performance

The REIMAGINE 2 trial compared CagriSema across multiple dose levels against semaglutide monotherapy in adults with type 2 diabetes. Results demonstrated that CagriSema consistently outperformed the standard GLP-1 therapy across all tested doses. The HbA1c reduction magnitude (1.91%-points) positions this combination therapy as a meaningful advancement for patients requiring intensive glycemic control.

Weight reduction outcomes paralleled the HbA1c benefits, with patients achieving approximately 14.2% body weight reduction—a substantial outcome that addresses the comorbid obesity often accompanying type 2 diabetes.

Safety and Tolerability Profile

CagriSema demonstrated a safe and well-tolerated adverse event profile consistent with established incretin and amylin-based therapies. The safety data support continued development across both indications, with no unexpected tolerability concerns emerging during the extended trial period.

Development Roadmap and Regulatory Strategy

Novo Nordisk is advancing CagriSema through parallel development programs. The REDEFINE programme investigates the therapy in adults with overweight or obesity, while the REIMAGINE programme focuses on type 2 diabetes management. Following positive REIMAGINE 1 and REDEFINE 3 trial outcomes, the company plans regulatory discussions with health authorities regarding CagriSema’s clinical development pathway.

The company submitted CagriSema for weight management to the US FDA in December 2025, based on REDEFINE 1 and REDEFINE 2 pivotal trial data. Detailed REIMAGINE 2 results will be presented at a major scientific conference in 2026, providing the medical community with comprehensive efficacy and HbA1c control analyses.

Significance as First-in-Class Amylin-Based Combination

Martin Holst Lange, executive vice president and chief scientific officer at Novo Nordisk, emphasized that combining semaglutide with cagrilintide yields superior HbA1c management and weight reduction beyond monotherapy achievements. If approved, CagriSema would represent the first amylin-based combination therapy, offering a novel treatment avenue for type 2 diabetes patients prioritizing comprehensive metabolic control.

The HbA1c reduction data positions CagriSema as a potentially transformative option for patients experiencing inadequate glycemic control or insufficient weight management with existing GLP-1 therapies alone.