CagriSema Delivers Superior HbA1c and Weight Reduction Across Phase 3 REIMAGINE Diabetes Trials

Novo Nordisk presented late‑breaking Phase 3 results from the REIMAGINE 1–3 trials at the ADA 2026 Scientific Sessions, simultaneously published in The Lancet and The Lancet Diabetes & Endocrinology. Once‑weekly CagriSema achieved significant reductions in HbA1c and body weight in adults with type 2 diabetes (T2D), including those managed with lifestyle intervention, metformin‑based therapy, and basal insulin.

All three studies met primary glycemic endpoints and confirmatory secondary endpoints for weight reduction.

Dual‑Hormone Approach Targets Glycemic Control and Weight Loss

CagriSema combines cagrilintide, a novel long‑acting amylin analog, with semaglutide, a GLP‑1 receptor agonist. Together, they regulate complementary pathways in appetite control, gastric emptying, glucose metabolism, and weight regulation. This dual‑hormone strategy addresses two persistent challenges in T2D management: durable glycemic control and sustained weight loss, both critical to reducing cardiometabolic risk.

REIMAGINE Trials Demonstrate Consistent Efficacy

The REIMAGINE 1 study (NCT06323174) enrolled 189 adults with T2D inadequately controlled through lifestyle measures, with a mean baseline HbA1c of 7.8%. At week 40, CagriSema 2.4 mg/2.4 mg reduced HbA1c by 1.8 percentage points and body weight by 13.8%, compared with reductions of 0.1 percentage points and 1.4% with placebo (p<0.0001). The lower‑dose regimen achieved HbA1c and weight reductions of 1.5 percentage points and 11.8%, confirming efficacy even at reduced dosing.

The REIMAGINE 2 trial (NCT06065540) enrolled 2,713 adults inadequately controlled on metformin with or without an SGLT2 inhibitor, with a mean baseline HbA1c of 8.2%. Over 68 weeks, CagriSema 2.4 mg/2.4 mg reduced HbA1c by 1.91 percentage points and body weight by 14.2%, outperforming semaglutide 2.4 mg, which achieved reductions of 1.75 percentage points and 10.2%. The differences were statistically significant for both glycemic control (p=0.0035) and weight loss (p<0.0001). The lower‑dose regimen also outperformed semaglutide 1 mg, underscoring the added contribution of amylin analog therapy.

In REIMAGINE 3 (NCT06323161), 274 adults receiving basal insulin with or without metformin and with the highest mean baseline HbA1c of 8.8% were studied. At week 40, CagriSema 2.4 mg/2.4 mg reduced HbA1c by 2.33 percentage points and body weight by 12.0%, compared with reductions of 0.66 percentage points and a 1.1% increase in body weight with placebo, highlighting robust efficacy even in insulin‑treated patients.

Safety Profile Consistent with Incretin Therapies

Gastrointestinal adverse events were the most frequently reported side effects, consistent with GLP‑1‑based therapies and generally mild to moderate. In REIMAGINE 2, GI events occurred in 67.2% of participants receiving high‑dose CagriSema compared with 53.9% of those on semaglutide 2.4 mg. Treatment discontinuations remained relatively low, occurring in 8.5% of participants receiving high‑dose CagriSema. No new safety signals emerged across the program.

Advancing Dual‑Hormone Therapy in Diabetes

Martin Holst Lange, Executive Vice President and Head of R&D at Novo Nordisk, said the consistent efficacy across diverse T2D populations supports CagriSema’s potential as the first amylin–GLP‑1 combination therapy for diabetes management.

The REIMAGINE findings build on results from the REDEFINE obesity program and strengthen the rationale for dual‑hormone therapy. Novo Nordisk has submitted a U.S. NDA for CagriSema in chronic weight management, with a regulatory decision expected in Q4 2026. Ongoing REIMAGINE 4 and 5 trials comparing CagriSema with tirzepatide will further define its competitive positioning in the evolving diabetes and obesity treatment landscape.

Reference

Novo Nordisk’s CagriSema 2.4 mg / 2.4 mg demonstrated significant reduction in HbA1c and weight across multiple studies in the REIMAGINE program presented at ADA 2026