Novo Nordisk CagriSema Phase 3 trials show large HbA1c and weight reductions

Program and trial design

REIMAGINE 1–3 are phase 3 studies of once‑weekly CagriSema, a fixed‑dose combination of the long‑acting amylin analog cagrilintide and the GLP‑1 receptor agonist semaglutide. REIMAGINE 1 was a 40‑week placebo‑controlled trial in 189 adults inadequately controlled on diet and exercise. REIMAGINE 2 was a 68‑week active‑comparator study in 2,713 adults on metformin ± SGLT2 inhibitor versus semaglutide (1 mg and 2.4 mg), cagrilintide 2.4 mg and placebo. REIMAGINE 3 was a 40‑week add‑on‑to‑basal‑insulin study in 274 adults.

Efficacy results

All three trials met primary HbA1c and confirmatory weight endpoints. Reported efficacy (efficacy estimand) for CagriSema 2.4 mg/2.4 mg included HbA1c reductions of −1.8% (REIMAGINE 1), −1.91% (REIMAGINE 2) and −2.33% (REIMAGINE 3). Relative bodyweight changes were −13.8% (REIMAGINE 1), −14.2% (REIMAGINE 2) and −12.0% (REIMAGINE 3); REIMAGINE 2 showed statistical superiority versus semaglutide 2.4 mg for weight (p<0.0001) and for HbA1c (p=0.0035).

Safety profile

The most common adverse events across trials were gastrointestinal. Reported GI rates for CagriSema 2.4/2.4 mg ranged roughly 53–67% across studies, with trial‑product discontinuations up to 8.5% in REIMAGINE 2; discontinuation rates were lower in the semaglutide and placebo arms in the same trials.

Regulatory and dissemination

REIMAGINE 1 and 2 results were published in The Lancet Diabetes & Endocrinology and REIMAGINE 3 in The Lancet and were presented at the ADA Scientific Sessions (June 5–8, 2026). Novo Nordisk filed an NDA for CagriSema for weight management in December 2025; a regulatory decision is expected in Q4 2026.