In a recent development, Novo Nordisk A/S announced the headline results of its REIMAGINE 2 phase 3 clinical trial assessing the efficacy and safety of CagriSema for weight management and glycemic control. CagriSema is a fixed-dose combination of cagrilintide and semaglutide, administered once weekly via subcutaneous injection. This medication seeks to provide improved therapeutic outcomes for individuals with type 2 diabetes struggling to control their condition effectively.
The REIMAGINE 2 study spanned a 68-week period during which various doses of CagriSema (2.4 mg/2.4 mg and 1.0 mg/1.0 mg) were compared against corresponding doses of semaglutide (2.4 mg and 1.0 mg), cagrilintide alone at 2.4 mg, and placebo. The trial enrolled 2,728 participants diagnosed with type 2 diabetes exhibiting inadequate glycemic control despite treatment with metformin, with or without concurrent use of a sodium-glucose co-transporter 2 (SGLT2) inhibitor. Notably, around 40% of participants were already on SGLT2 inhibitors prior to beginning the study.
The investigation focused on evaluating the degree of reduction in glycated hemoglobin (HbA1c) and percentage of body weight loss achieved by trial subjects. At the commencement of the trial, the mean HbA1c level among participants was 8.2%, and the average body weight was approximately 101 kilograms.
Results at week 68 revealed that patients treated with the higher dose of CagriSema (2.4 mg/2.4 mg) experienced an average HbA1c reduction of 1.91 percentage points, surpassing the 1.76 percentage point decrease observed in those receiving semaglutide at 2.4 mg. In terms of weight loss, recipients of the high-dose combination medication achieved a 14.2% reduction in body weight, which significantly exceeded the 10.2% reduction seen in the semaglutide 2.4 mg group. The trial data indicated no evidence of weight loss reaching a plateau at the conclusion of the 68 weeks, suggesting sustained efficacy over time.
Additional analysis using the treatment regimen estimand, which considers treatment adherence and dosing, demonstrated that patients on the CagriSema 2.4 mg/2.4 mg regimen attained a 1.80 percentage point decline in HbA1c versus a 1.68 percentage point reduction with semaglutide 2.4 mg. Moreover, weight loss was 12.9% in the combination therapy group compared to 9.2% in the semaglutide cohort under this framework.
A substantial proportion of participants receiving CagriSema achieved clinically meaningful weight loss milestones: 43% lost at least 15% of their baseline body weight, while 24% attained reductions of 20% or more. The safety profile of CagriSema was consistent with expectations for incretin and amylin-based therapies. Adverse events were predominantly gastrointestinal in nature, mostly mild to moderate in severity, and typically diminished over time.
This data builds upon Novo Nordisk’s previous regulatory activities, including the December 2025 submission of CagriSema for weight management to the U.S. Food and Drug Administration, supported by earlier pivotal trials named REDEFINE 1 and REDEFINE 2. The REIMAGINE 2 trial is a component of the company's broader global REIMAGINE clinical program.
Following the announcement, shares of Novo Nordisk were observed trading slightly lower at $59.07, down 0.61%, according to market data at the time of publication.
Key Points:
- CagriSema, a fixed-dose combination of cagrilintide and semaglutide, outperformed semaglutide alone in reducing HbA1c and body weight over 68 weeks among type 2 diabetes patients on metformin +/- SGLT2 inhibitors.
- The trial enrolled 2,728 patients with a baseline mean HbA1c of 8.2% and mean weight of 101 kg.
- High-dose CagriSema (2.4 mg/2.4 mg) led to a 1.91 percentage point HbA1c reduction and 14.2% body weight loss, exceeding outcomes for semaglutide 2.4 mg.
- CagriSema’s safety profile was manageable with mostly mild to moderate gastrointestinal side effects.
Risks and Uncertainties:
- Gastrointestinal adverse events, typical for drugs acting on incretin and amylin receptors, could impact patient adherence despite most symptoms being mild to moderate and decreasing over time.
- Long-term sustainability beyond 68 weeks is not established; no weight loss plateau was observed within the trial period but extended outcomes are unknown.
- The trial population included patients inadequately controlled on metformin and possibly SGLT2 inhibitors, so results might not generalize to all type 2 diabetes populations.
- Regulatory review outcomes remain pending; although CagriSema has been submitted for FDA approval, future approval is subject to regulatory assessment.