CagriSema (Cagrilintide + Semaglutide)

CagriSema is Novo Nordisk's investigational fixed-dose combination of cagrilintide 2.4 mg (a long-acting amylin analogue) and semaglutide 2.4 mg, delivered as a single once-weekly subcutaneous injection. It represents a novel dual-hormone approach to weight management that goes beyond the GLP-1 receptor alone by adding amylin receptor activation. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells, and it plays complementary roles in appetite suppression: it slows gastric emptying, suppresses glucagon secretion, and produces satiety signals via the central nervous system, particularly the area postrema and hypothalamus — pathways that are partially distinct from GLP-1 signaling. The hypothesis underlying CagriSema is that dual-pathway engagement produces additive or synergistic weight loss beyond what semaglutide achieves alone. The REDEFINE 1 Phase 3 trial in adults with obesity or overweight (without type 2 diabetes) reported impressive results: among participants evaluated for the treatment effect if all patients stayed on treatment, average weight loss was 22.7% at approximately 68 weeks. The full population analysis showed 20% average weight loss. Crucially, 91.9% of CagriSema-treated participants achieved at least 5% weight reduction, compared to 31.5% with placebo. Approximately one-third of participants reached 25% or greater weight loss, approaching surgical outcomes. Novo Nordisk submitted an NDA to the FDA on December 18, 2025, making CagriSema the most advanced next-generation obesity drug in the regulatory pipeline. The FDA is expected to complete its review in 2026, with a potential approval decision by late 2026 or early 2027. CagriSema is not yet approved in the US or EU. If approved, it would be the first amylin-class drug approved for obesity, representing a new mechanistic pillar in the field.