CagriSema shows strong blood sugar and weight loss results in phase 3 diabetes trials

Novo Nordisk reported significant reductions in HbA1c and body weight with its investigational once-weekly therapy CagriSema across three phase 3 REIMAGINE studies in adults with type 2 diabetes, findings presented at the American Diabetes Association Scientific Sessions 2026.

Novo Nordisk on 7 June unveiled phase 3 data showing that CagriSema, an investigational combination of cagrilintide and semaglutide, significantly reduced both HbA1c and body weight in adults with type 2 diabetes across multiple stages of disease management.

The findings, presented at the 2026 Scientific Sessions of the American Diabetes Association (ADA) in New Orleans, are notable because they suggest a single once-weekly treatment could address two key challenges in type 2 diabetes care: blood glucose control and weight management. The results were drawn from the REIMAGINE clinical development programme, which evaluated CagriSema in adults with type 2 diabetes ranging from newly treated patients to those already receiving basal insulin.

What is CagriSema?

CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist.

Amylin is a pancreatic hormone released alongside insulin after meals. It is involved in appetite regulation, glycaemic control, bone metabolism and body weight regulation. Semaglutide is a widely used GLP-1 receptor agonist that helps lower blood glucose and support weight loss.

According to Novo Nordisk, combining these two mechanisms is intended to target multiple pathways involved in type 2 diabetes.

“The REIMAGINE 1-3 studies showed promising results by combining a novel amylin analog with the proven significant effects of semaglutide for HbA1c reduction and weight loss in adults living with type 2 diabetes,” said Martin Holst Lange, Executive Vice President and Chief Scientific Officer at Novo Nordisk.

Lange said the consistency of results across patients at different stages of disease progression was particularly encouraging and suggested the therapy could become the first amylin and GLP-1 combination treatment for type 2 diabetes.

Results across three phase 3 studies

The REIMAGINE programme met its primary endpoint in all three trials, demonstrating significant reductions in HbA1c. The studies also achieved confirmatory secondary endpoints related to body weight reduction.

The programme included:

• REIMAGINE 1, a 40-week study involving 189 adults with type 2 diabetes inadequately controlled through diet and exercise.
• REIMAGINE 2, a 68-week study involving 2,713 adults whose diabetes remained inadequately controlled despite metformin, with or without an SGLT2 inhibitor.
• REIMAGINE 3, a 40-week study involving 274 adults receiving basal insulin, with or without metformin.

Results from REIMAGINE 1 and REIMAGINE 2 were published in The Lancet Diabetes & Endocrinology, while REIMAGINE 3 was published in The Lancet.

John B. Buse, Distinguished Professor of Medicine and Director of the UNC Diabetes Care Center, said the medical community has recognised the therapeutic potential of amylin in type 2 diabetes for many years.

“Now, in the REIMAGINE trials, we’re taking that knowledge forward by exploring the combination of cagrilintide, a novel long-acting amylin receptor agonist, paired with semaglutide,” Buse said. He added that the approach was designed to address multiple pathways of glucose regulation and may offer benefits for patients who require a different strategy for managing type 2 diabetes.

Safety profile

Across all three studies, the most commonly reported adverse events were gastrointestinal in nature.

In REIMAGINE 1, gastrointestinal adverse events were reported in 53% of participants receiving CagriSema 2.4 mg/2.4 mg, compared with 20% in the placebo group.

In REIMAGINE 2, gastrointestinal adverse events occurred in 67.2% of participants receiving CagriSema 2.4 mg/2.4 mg, compared with 53.9% among those receiving semaglutide 2.4 mg and 28.2% in the placebo group.

In REIMAGINE 3, gastrointestinal adverse events were reported in 57% of participants receiving CagriSema 2.4 mg/2.4 mg, compared with 23% in the placebo group.

Discontinuations due to adverse events were reported across all treatment groups but remained relatively low in the studies.

What comes next?

The REIMAGINE programme builds on Novo Nordisk’s earlier REDEFINE programme, which evaluated CagriSema in adults with overweight or obesity, with and without type 2 diabetes.

Novo Nordisk is also conducting REIMAGINE 4 and REIMAGINE 5 trials comparing CagriSema with tirzepatide in adults with type 2 diabetes receiving standard care.

Separately, the company submitted a New Drug Application to the U.S. Food and Drug Administration in December 2025 seeking approval of CagriSema for weight management. A regulatory decision is expected in the fourth quarter of 2026.

For people living with type 2 diabetes, the latest phase 3 results indicate that combining amylin and GLP-1 pathways may offer a new approach to simultaneously improving blood glucose control and reducing body weight, two closely linked goals in diabetes management.