CagriSema Demonstrates Superior Hemoglobin and Weight Loss Results in Type 2 Diabetes

Novo Nordisk announced headline results from the REIMAGINE 2 (NCT06065540) phase 3 trial, revealing that its experimental therapy, CagriSema, achieved statistically significant superiority in both blood glucose control and weight reduction for adults with type 2 diabetes (T2D).¹

The once-weekly subcutaneous injection, a fixed-dose combination of the amylin receptor agonist cagrilintide and the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide, demonstrated a superior hemoglobin A_1c (HbA_1c) reduction of 1.91 percentage points from a baseline of 8.2%. Furthermore, patients treated with the 2.4 mg/2.4 mg dose of CagriSema achieved an average weight loss of 14.2% over 68 weeks, significantly outperforming the 10.2% weight loss seen in those using semaglutide 2.4 mg alone.

“We are very pleased by the clinical profile of CagriSema in type 2 diabetes patients, including a confirmation of the very strong weight loss data seen with CagriSema in the obesity trials,” Martin Holst Lange, executive vice president, chief scientific officer, and head of research and development at Novo Nordisk, said in a news release.

Clinical Program Highlights and Comparative Efficacy

The REIMAGINE 2 trial is a component of a broader clinical development program designed to address the needs of the 2728 individuals with T2D whose conditions were inadequately controlled by metformin or sodium-glucose cotransporter 2 inhibitors.¹

These latest findings reinforce data from the REDEFINE clinical trial program, which focuses on weight management. For instance, the REDEFINE 2 (NCT05394519) trial specifically evaluated patients with both type 2 diabetes and obesity, finding that 89.7% of participants achieved a weight loss of at least 5%.²

In the general obesity population studied in REDEFINE 1 (NCT05567796), CagriSema demonstrated even higher weight loss potential, with adherent patients losing 22.7% of their body weight compared to 16.1% for semaglutide alone.³

“By combining semaglutide and cagrilintide, we’re seeing superior outcomes in both blood glucose control and weight reduction beyond those achieved with each therapy individually,” Holst Lange said in the news release.¹ “The results strengthen our belief that CagriSema could be the first amylin-based combination therapy and a promising treatment option for individuals with type 2 diabetes, who also has a focus on weight loss.”

Although CagriSema has shown clear superiority over its individual components, the pharmaceutical landscape remains highly competitive. External data noted in recent clinical discussions indicates that tirzepatide has shown a 47% greater relative weight loss compared to semaglutide alone in the SURMOUNT-5 (NCT05822830) trial.²

Specifically, tirzepatide facilitated an average weight loss of 20.2%, which remains higher than the 14.2% to 15.7% established for CagriSema in populations with T2D. However, there was no weight loss plateau observed for CagriSema at the 68-week mark in the REIMAGINE 2 trial, suggesting potential for continued reduction beyond the study period.^1,2

Safety Profile and Considerations for Pharmacists

For pharmacists monitoring patient transitions to next-generation incretin therapies, CagriSema’s safety profile appears consistent with established GLP-1 and amylin-based treatments. The most common adverse events reported across the REIMAGINE and REDEFINE trials were gastrointestinal, with the majority being mild to moderate in severity and waning over time.^1,2

The fixed-dose combination aims to simplify regimens for patients who require both glycemic control and significant weight management, potentially improving adherence through a single weekly subcutaneous injection.^1,3

The trial protocols also utilized flexible dosing, which allowed investigators to modify patient doses throughout the studies, a factor that may reflect real-world clinical management.³ In the REDEFINE 2 trial, approximately 61.9% of patients reached the highest dose by the end of the 68-week period, while in REIMAGINE 2, the higher dose of 2.4 mg/2.4 mg was explicitly linked to the most robust HbA1c and weight outcomes.^1,2

Novo Nordisk already submitted CagriSema for weight management to the FDA in December 2025, supported by the REDEFINE 1 and 2 trials. Following the successful headline results from REIMAGINE 2, the company plans to approach regulatory authorities to discuss the approval pathway for the drug's use in T2D.¹

Detailed results from the REIMAGINE 2 trial are expected to be presented at scientific conferences throughout 2026. If approved, CagriSema could become the first amylin-based combination therapy available for patients managing the dual challenges of T2D and obesity.¹

READ MORE: Diabetes Resource Center

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REFERENCES

1. 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. News release. Novo Nordisk. February 2, 2026. Accessed February 3, 2026. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916481

2. Gallagher A. CagriSema demonstrates significant weight loss at 68 weeks. Drug Topics. March 12, 2025. Accessed February 3, 2026. https://www.drugtopics.com/view/cagrisema-demonstrates-significant-weight-loss-at-68-weeks

3. Biscaldi L. CagriSema demonstrates statistically significant, superior weight loss vs placebo. Drug Topics. December 20, 2024. Accessed February 3, 2026. https://www.drugtopics.com/view/cagrisema-demonstrates-statistically-significant-superior-weight-loss-vs-placebo