CagriSema

CagriSema is a fixed-dose co-formulation combining cagrilintide (a long-acting amylin analogue) and semaglutide (a GLP-1 receptor agonist), both at 2.4 mg, administered as a single weekly subcutaneous injection. Developed by Novo Nordisk, it is the most effective weight-loss peptide combination in Phase 3 trials as of 2026, achieving mean body weight reductions exceeding 20% in non-diabetic adults over 68 weeks.

CagriSema harnesses two complementary appetite-regulating pathways. Semaglutide activates GLP-1 receptors in the hypothalamus, hindbrain, and vagus nerve, suppressing appetite, slowing gastric emptying, and improving insulin secretion. Cagrilintide mimics amylin, a pancreatic hormone co-secreted with insulin that acts on area postrema and nucleus tractus solitarius receptors to promote satiety, reduce food intake, and modulate glucagon secretion. The dual mechanism produces additive to synergistic appetite suppression through both hedonic and homeostatic neural pathways, which appears to underpin the superior weight loss versus either agent alone.

The REDEFINE 1 Phase 3 trial (68 weeks, non-diabetic adults with obesity) found a mean 20.4% body weight reduction with CagriSema versus 3.0% placebo. Approximately 60% of participants lost at least 20% of body weight, and 23% lost 30% or more. REDEFINE 2 (type 2 diabetes) showed 13.7% mean weight reduction. Both trials reported higher rates of gastrointestinal adverse events (79.6%) versus placebo (39.9%), primarily nausea, vomiting, and constipation, which were mostly transient and mild-to-moderate. Regulatory submission was anticipated in 2025–2026.

Peptides commonly paired with CagriSema for synergistic effects.