Novo Nordisk CagriSema Phase 3 trials show large HbA1c and weight reductions
- CagriSema produced HbA1c reductions of −1.8% (REIMAGINE 1, 40 weeks), −1.91% (REIMAGINE 2, 68 weeks) and −2.33% (REIMAGINE 3, 40 weeks).
- Relative bodyweight reductions were −13.8% (REIMAGINE 1), −14.2% (REIMAGINE 2; statistically superior to semaglutide 2.4 mg, p<0.0001) and −12.0% (REIMAGINE 3).
- REIMAGINE 2 enrolled 2,713 adults on metformin ± SGLT2 inhibitors and compared CagriSema versus semaglutide, cagrilintide and placebo; REIMAGINE 1 (n=189) tested diet/exercise patients and REIMAGINE 3 (n=274) tested add‑on to basal insulin.
- Gastrointestinal events were the most common adverse events (CagriSema 2.4/2.4: ~53–67% across trials) with discontinuations up to 8.5% in REIMAGINE 2; an NDA for weight management was filed Dec 2025 with a decision expected Q4 2026.
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.
Source: Novo Nordisk