Cagrilintide

Cagrilintide is a synthetic long-acting analog of human amylin developed by Novo Nordisk. The peptide is studied for the management of obesity and is most commonly combined with the GLP-1 analog semaglutide in the CagriSema investigational dual-agonist program.

Peppudex card: see the mechanism + evidence-grade summary at [Peppudex / Cagrilintide](https://peppudex.com/peptides/cagrilintide).

Overview

Native amylin is a 37-amino-acid peptide co-secreted with insulin by pancreatic beta cells. It promotes satiety, slows gastric emptying, and reduces postprandial glucagon. The native peptide has a short half-life and poor solubility, which led to multiple synthetic analogs: pramlintide (Symlin · FDA-approved 2005) for insulin-treated diabetes, and cagrilintide as a once-weekly improvement designed for weight-management studies.

Mechanism

Cagrilintide is a dual amylin and calcitonin receptor agonist (DACRA). It binds both the amylin receptor (a heterodimer of the calcitonin receptor with RAMP1/2/3) and the calcitonin receptor itself. Both receptors are expressed in the area postrema and arcuate nucleus, where signaling reduces food intake and promotes satiety.

See: GLP-1_receptor (complementary mechanism in CagriSema).

Evidence

Cagrilintide is in late-stage clinical development:

• REDEFINE 1 (NCT05567796) · Phase 3 trial of CagriSema (cagrilintide + semaglutide) for obesity. Topline data reported 2024-2026.
• Phase 2 monotherapy · 26-week trial in obesity showed dose-dependent weight loss (Lau et al., Lancet 2021; PMID 34247670).

The combination with semaglutide (CagriSema) targets both the amylin and GLP-1 axes and has reported placebo-subtracted weight loss in the 15-22% range in Phase 2.

Dosing literature

Clinical trials have used subcutaneous 2.4 mg once weekly (matching the semaglutide dosing rhythm). The wiki does not recommend any human dose; cagrilintide is investigational.

Pharmacokinetics

Cagrilintide is engineered with a C20 fatty-diacid linker that drives albumin binding, extending half-life from native amylin's ~13 minutes to approximately 7 days. Once-weekly subcutaneous dosing matches the semaglutide rhythm used in the CagriSema combination program. Steady-state plasma concentration is reached after 4 to 5 weeks of repeated dosing.

Storage

Lyophilized cagrilintide is stable at –20 °C for at least 24 months. Once reconstituted with bacteriostatic water, store at 2-8 °C and use within 28 days.

Regulatory status

• United States. Investigational. Not yet FDA-approved as of 2026-05; Phase 3 program ongoing.
• WADA. Not listed on the 2024 Prohibited List. May fall under S2 (peptide hormones) at regulator discretion.

Side effects (per published Phase 2)

Adverse events reported in the Lau 2021 Phase 2 trial were predominantly gastrointestinal (nausea, vomiting, diarrhea) and largely dose-dependent. Injection-site reactions were observed at a higher rate than placebo. Hypoglycemia was uncommon without concomitant insulin. The CagriSema combination Phase 2 data show GI adverse events at rates similar to semaglutide alone.

See also

• Semaglutide · combined partner in CagriSema
• GLP-1_receptor · complementary axis
• Liraglutide · prior-generation GLP-1 analog
• Reconstitution · vial-prep math
• [Peppudex card · Cagrilintide](https://peppudex.com/peptides/cagrilintide) · mechanism, evidence grades A-F, FAQs, peer-reviewed sources

References

• Lau DCW, et al. "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." Lancet. 2021;398(10317):2160-2172. PMID 34247670.
• Frias JP, et al. "Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes." Lancet. 2023;402(10403):720-730. PMID 37364590.