Novo Nordisk’s CagriSema showed superior HbA1c reductions (1.91%) and weight loss (14.2%) vs semaglutide in REIMAGINE 2 phase 3 trial for type 2 diabetes. Learn trial details, safety, and regulatory plans.
Written By: Nikita Chaudhari BPharm
Reviewed By: Pharmacally Editorial Team
Novo Nordisk announced positive results from REIMAGINE 2, a phase 3 trial of CagriSema in adults with type 2 diabetes. This once-weekly subcutaneous injection reduced HbA1c and body weight more than semaglutide alone across all doses at week 68. The findings highlight CagriSema’s potential for improved glycemic and weight management.
CagriSema is a fixed-dose combination of cagrilintide, an amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. The two agents provide complementary effects that outperform either monotherapy.
Martin Holst Lange, Executive Vice President and Chief Scientific Officer at Novo Nordisk, stated: “The results confirm the strong weight loss observed in obesity trials. CagriSema outperforms each component alone and could become the first amylin-based combination therapy for type 2 diabetes with a focus on weight management.”
REIMAGINE 2 Trial
REIMAGINE 2 enrolled 2,728 adults with type 2 diabetes inadequately controlled on metformin, with or without SGLT2 inhibitors (about 40% on SGLT2 inhibitors). Baseline mean HbA1c was 8.2%, and mean body weight was 101 kg.
The 68-week trial compared CagriSema (2.4 mg/2.4 mg and 1.0 mg/1.0 mg) against semaglutide (2.4 mg and 1.0 mg), cagrilintide 2.4 mg, and placebo. It evaluated long-term glycemic control and weight loss.
From the efficacy/adherence estimand, CagriSema 2.4 mg/2.4 mg delivered:
- HbA1c reduction of 1.91 percentage points (vs. 1.76 points with semaglutide 2.4 mg).
- Weight reduction of 14.2% (vs. 10.2%).
No weight loss plateau occurred at week 68, indicating potential for further reductions. Proportionally, 43% of participants achieved ≥15% weight loss; 24% achieved ≥20%.
Using the treatment-regimen estimand, CagriSema remained superior: HbA1c reduction of 1.80 points and weight loss of 12.9% (vs. 1.68 points and 9.2% for semaglutide).
Safety and Tolerability
CagriSema showed a favorable safety profile, consistent with GLP-1 and amylin receptor therapies. The most common adverse events were gastrointestinal and mostly mild to moderate, decreasing over time.
Regulatory Path and Next Steps
Novo Nordisk will discuss regulatory pathways for type 2 diabetes approval, building on REIMAGINE 1 and REDEFINE 3. Detailed REIMAGINE 2 results will be presented at a scientific conference in 2026. For weight management, the company submitted to the US FDA in December 2025 based on REDEFINE 1 and 2.
Broader REIMAGINE Phase 3 Program
REIMAGINE 2 supports Novo Nordisk’s global phase 3 program evaluating CagriSema across type 2 diabetes populations, including those on oral antidiabetics, basal insulin, and head-to-head versus tirzepatide. Key ongoing trials include REIMAGINE 4 (CagriSema vs. tirzepatide 15 mg) and REIMAGINE 5 (Lower-dose CagriSema vs. tirzepatide 5 mg).
References
Novo Nordisk A/S: CagriSema demonstrated superior HbA1c reduction of 1.91%-points and weight loss of 14.2% in adults with type 2 diabetes in the REIMAGINE 2 trial, 2 February 2026, News Details
A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor (REIMAGINE 2), ClinicalTrials.gov ID NCT06065540, https://clinicaltrials.gov/study/NCT06065540