Cagrilintide is a synthetic peptide analog of amylin, a hormone co-secreted with insulin by pancreatic beta cells. It acts as a dual agonist for the amylin receptor (primarily through calcitonin receptor complexes) and has partial GLP-1 receptor activity. Developed by Novo Nordisk, it’s primarily investigated for obesity and type 2 diabetes management, often in combination with semaglutide (a GLP-1 agonist) under the investigational name CagriSema.

Mechanism of Action

• Amylin mimicry: Slows gastric emptying, promotes satiety via central nervous system signaling (e.g., in the area postrema), and reduces postprandial glucagon secretion.
• Synergy with GLP-1: When combined, it enhances weight loss beyond GLP-1 alone by targeting multiple pathways: appetite suppression, delayed digestion, and energy expenditure.
• Evidence: Phase 2 trials (e.g., REINFORCE program) showed up to 15-20% body weight reduction over 32-68 weeks when co-administered with semaglutide, outperforming semaglutide monotherapy (10-15% loss). A 2023 NEJM study on CagriSema reported 22.7% weight loss at 68 weeks vs. 16.5% for semaglutide alone (p<0.001).

Clinical Status

Peptide Structure and Synthesis Notes

• Sequence: Ac-[Lys1hArg26]-cagrilintide (32-amino acid chain with modifications for stability, e.g., C2-C7 disulfide bridge, lipidation at Lys26 for extended half-life ~1 week).
• Synthesis: Typically via solid-phase peptide synthesis (SPPS) using Fmoc chemistry. Key challenges: correct disulfide formation, purity >95% via HPLC. Not commercially available for research yet; custom synthesis from peptide suppliers (e.g., ~$500-2000/mg depending on scale/quality).
• Molecular Weight: ~3,800 Da.

Availability and Use

• Research: Available via research chemical suppliers (e.g., Peptide Sciences, Limitless Life) as lyophilized powder for lab use (not human consumption). Purity claims 98-99%; verify with MS/HPLC COAs.
• Legality: Unscheduled in most countries; for research only. Self-administration risky—lacks clinical dosing data outside trials.
• Ongoing Trials: >10,000 patients in Phase 3 for obesity/T2D; potential launch 2026 if successful.

For latest data, check ClinicalTrials.gov (NCT# for CagriSema: NCT04982562) or Novo Nordisk pipeline. If you’re synthesizing or studying it, ensure biosafety level 1+ protocols. Questions on specifics?