Novo Nordisk's CagriSema Delivers Superior HbA1c Reduction in Type 2 Diabetes Trial

Novo Nordisk A/S unveiled breakthrough outcomes from the REIMAGINE 2 trial this week, demonstrating that CagriSema significantly improves both HbA1c reduction and weight loss compared to semaglutide monotherapy. The dual-component treatment combines cagrilintide, a long-acting amylin receptor agonist, with semaglutide, a long-acting GLP-1 receptor agonist, addressing two key mechanisms in blood glucose management and metabolic control.

Enhanced Blood Glucose Control and Weight Loss Outperform Individual Therapies

The 68-week efficacy and safety trial revealed compelling clinical results that underscore CagriSema’s therapeutic potential. Patients receiving the combination therapy achieved a 1.91%-point reduction in HbA1c—a critical marker of long-term blood glucose control—along with an average weight loss of 14.2%. These outcomes were consistently superior across all tested doses when compared to semaglutide alone.

Critically, CagriSema demonstrated greater efficacy than either component used individually. This superiority in both HbA1c improvement and weight reduction highlights the synergistic benefits of the combination approach. The trial also confirmed a favorable safety profile consistent with incretin and amylin-based therapies, with no unexpected safety signals emerging during the study period.

First Amylin-Based Combination Therapy on Regulatory Track

CagriSema represents a notable innovation in diabetes therapeutics as a pioneering amylin-based combination therapy. Building on positive results from REIMAGINE 1 and REDEFINE 3 trials, Novo Nordisk is advancing toward regulatory discussions with health authorities regarding the approval pathway for type 2 diabetes treatment.

The company is investigating once-weekly subcutaneous CagriSema through two parallel programs: REIMAGINE for adults with type 2 diabetes, and REDEFINE for weight management in individuals with overweight or obesity. The regulatory momentum accelerated following FDA submission for CagriSema’s weight management indication in December 2025, based on REDEFINE 1 and REDEFINE 2 pivotal trials.

What This Means for Type 2 Diabetes Treatment Options

Martin Holst Lange, executive vice president and chief scientific officer at Novo Nordisk, emphasized the clinical significance: “By combining semaglutide and cagrilintide, we’re achieving superior outcomes in both blood glucose control and weight reduction beyond what each therapy delivers individually. These results strengthen our conviction that CagriSema could establish a new treatment paradigm for type 2 diabetes patients who require robust HbA1c management alongside meaningful weight loss.” The company plans to present comprehensive REIMAGINE 2 data at a major scientific conference in 2026, providing additional insights into the therapy’s long-term benefits and patient outcomes.

Market response to the announcement proved modest, with Novo Nordisk’s stock declining 0.8% to close at $58.93 on the announcement day, though shares recovered to $59.19 in subsequent overnight trading, suggesting measured investor confidence in the program’s progression.