What is Cagrilintide?
Cagrilintide (development code AM833, also NN9838) is a long-acting analogue of human amylin developed by Novo Nordisk. It is engineered to act as a dual agonist at the amylin receptor (AMY) and the calcitonin receptor (CTR), which mediate complementary effects on satiety, glucose homeostasis, and gastric emptying.
It is one of the two components of CagriSema — a once-weekly fixed-dose combination of cagrilintide plus semaglutide — which is the most-watched obesity drug candidate of 2025–2026 and has been submitted to the FDA for chronic weight management.
Mechanism of Action
Native amylin is co-secreted with insulin from pancreatic β-cells in response to food intake and signals satiety to the central nervous system. Cagrilintide is structurally modified to extend its half-life to approximately one week:
- Substitution of pramlintide-like residues to prevent self-aggregation
- Addition of a C20 fatty acid chain (acylation at Lys26) for albumin binding
- Net effect: once-weekly subcutaneous dosing
Cagrilintide activates AMY1, AMY2, AMY3, and CTR receptors, suppressing appetite via hindbrain area postrema circuits, slowing gastric emptying, and reducing postprandial glucagon. The mechanism is non-incretin and complementary to GLP-1 agonism — which is why it is paired with semaglutide rather than competing with it.
Clinical Evidence
Cagrilintide monotherapy (Phase 2, Lancet 2021):
- Once-weekly dosing of cagrilintide produced 6.0–10.8% weight loss at 26 weeks across doses (0.3 mg to 4.5 mg) vs 3.0% with placebo and 9.4% with liraglutide 3.0 mg.
REDEFINE-1 (Phase 3, NEJM 2025) — CagriSema combination:
- 3,417 adults with obesity (BMI ≥30) without diabetes, randomized to once-weekly CagriSema, semaglutide alone, cagrilintide alone, or placebo for 68 weeks.
- CagriSema: 20.4% mean weight loss (treatment-policy estimand)
- Semaglutide alone: 14.9%
- Cagrilintide alone: 11.5%
- Placebo: 3.0%
- Approximately 40% of CagriSema participants achieved ≥25% body-weight reduction.
REDEFINE-2 (Phase 3, T2D + obesity) and additional Phase 3 readouts in MASH and cardiovascular outcomes are ongoing.
Regulatory Status
Cagrilintide as a monotherapy remains in Phase 3 for obesity indications. The combination product CagriSema has been submitted to the FDA for chronic weight management in adults with obesity. As of mid-2026 it has not yet received an approval decision; analysts widely expect approval in late 2026 or 2027.
Why It Matters
The peptide and obesity-research communities are watching cagrilintide closely for two reasons:
- Mechanism stacking — CagriSema is the proof point that combining a GLP-1 with a complementary non-GLP-1 satiety pathway can push weight loss meaningfully beyond what semaglutide or tirzepatide achieve alone.
- Lean-mass preservation — early data suggest cagrilintide's amylin-receptor pharmacology may better preserve lean mass and metabolic rate compared to GLP-1 monotherapy, though head-to-head data are still maturing.
Cagrilintide is the first long-acting amylin analogue to reach late-stage development — distinct from pramlintide (Symlin), which is a much shorter-acting amylin analogue used as an adjunct to insulin in diabetes.