Cagrilintide: The Long-Acting Amylin Analogue, Its Structure and Research

Cagrilintide is a long-acting, lipidated analogue of the pancreatic hormone amylin, developed by Novo Nordisk. It acts on amylin and calcitonin receptors rather than on the incretin receptors that semaglutide, tirzepatide and retatrutide target, and it is being developed both on its own and with semaglutide as the combination CagriSema. It is investigational and not approved.

Cagrilintide at a glance

Formula from PubChem, which matches the structure; the FDA substance registry lists one oxygen fewer, which does not. Compared with human amylin (UniProt P10997), the backbone differs at six positions, including three prolines (A25P, S28P, S29P) of the kind pramlintide uses to stop amylin forming fibrils.

What makes cagrilintide different

Native amylin is co-secreted with insulin but is hard to use as a research tool or drug because it aggregates into amyloid fibrils. The earlier analogue pramlintide fixed that but has a short half-life. Novo Nordisk’s 2021 paper describes the structure-activity work that produced cagrilintide: a stable, non-aggregating amylin analogue with a fatty diacid for albumin binding, so it lasts long enough for once-weekly dosing in trials. In a phase 1b study its measured half-life was 159 to 195 hours.

Because it works on the amylin pathway, cagrilintide is usually studied next to, or combined with, an incretin agonist. CagriSema pairs it with semaglutide in one weekly product.

Published research on cagrilintide

• Development (2021). The medicinal-chemistry route to a long-acting, non-fibrillating amylin analogue, contrasted with pramlintide’s three daily injections. Development of Cagrilintide, a Long-Acting Amylin Analogue. Kruse T, et al. Journal of Medicinal Chemistry, 2021.
• Phase 1b with semaglutide (2021). In 96 adults, cagrilintide exposure was dose-proportional and did not change semaglutide’s exposure; half-lives were 159–195 h for cagrilintide and 145–165 h for semaglutide. Enebo LB, et al. Lancet, 2021.
• Phase 2 dose-finding (2021). A 26-week, placebo- and liraglutide-controlled trial in 706 adults; gastrointestinal disorders and administration-site reactions were the most frequent adverse events. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. Lau DCW, et al. Lancet, 2021.
• Phase 3 REDEFINE 1 and 2 (2025). 68-week trials of the cagrilintide–semaglutide combination in 3,417 adults without diabetes and 1,206 with type 2 diabetes. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. Garvey WT, et al. NEJM, 2025; Davies MJ, et al. NEJM, 2025.
• Phase 3 REIMAGINE 2 (2026). In 2,713 people with type 2 diabetes, the combination lowered HbA1c by 1.91 percentage points at 68 weeks against 1.75 with semaglutide alone. Buse JB, et al. Lancet Diabetes & Endocrinology, 2026.
• Review (2026). Cagrilintide as a dual amylin-receptor and calcitonin-receptor agonist and second-generation amylin analogue. Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes. Bailey CJ, et al. Peptides, 2026.

Novo Nordisk reported in February 2026 that CagriSema did not meet its non-inferiority endpoint against tirzepatide in the REDEFINE 4 head-to-head trial. Cagrilintide on its own is in phase 3 (RENEW 1 and 2).

Cagrilintide vs the incretin agonists

More on the incretin side in retatrutide vs semaglutide and GLP-1 vs GLP-2 vs GLP-3.

Regulatory status

Cagrilintide is not approved on its own or in combination. Novo Nordisk announced on 18 December 2025 that it had submitted CagriSema to FDA; no FDA label or decision was found as of 24 October 2026.