Cagrilintide

Cagrilintide is an investigational long-acting acylated analogue of amylin, a pancreatic hormone involved in satiety. It has been studied alone and in combination with semaglutide (CagriSema) for weight management.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Cagrilintide is a synthetic analogue of amylin, a peptide hormone co-secreted with insulin by pancreatic beta cells that contributes to satiety and slows gastric emptying. Native human amylin is prone to aggregation and is short-lived, which limits its use. Novo Nordisk developed cagrilintide as a stable, long-acting analogue suitable for once-weekly dosing by adding a fatty acid side chain for albumin binding.

Cagrilintide has been studied as a single agent and, more prominently, in combination with semaglutide under the name CagriSema. Phase 2 trials examined effects on body weight and glycemic control, and the combination has been evaluated in the REDEFINE phase 3 program. Cagrilintide is investigational and not approved. The only approved amylin analogue in the US is pramlintide (Symlin), a short-acting drug for diabetes.

Structure

Cagrilintide is an acylated analogue of amylin, a 37-residue peptide with an intramolecular disulfide bond near the N-terminus and an amidated C-terminus. It incorporates amino acid substitutions that reduce the strong aggregation tendency of native human amylin and is attached to a fatty acid side chain that promotes reversible albumin binding and extends its half-life. Its exact substitution pattern should be confirmed from primary sources before use as a reference.

Mechanism

Cagrilintide is an agonist at amylin receptors, which are complexes of the calcitonin receptor with receptor activity-modifying proteins (RAMPs). It also activates the calcitonin receptor itself, and is described as a non-selective amylin and calcitonin receptor agonist. Amylin signaling in the brainstem, particularly the area postrema, and the hypothalamus contributes to satiety and reduced food intake.

Amylin receptor activation also slows gastric emptying and suppresses postprandial glucagon secretion. Because amylin and GLP-1 act through different receptors and partly different brain pathways, combining cagrilintide with semaglutide was hypothesized to produce additive effects on appetite and body weight, which motivated the CagriSema program.

Research

Phase 2 monotherapy trial

A randomized, placebo-controlled phase 2 trial, published in The Lancet in 2021, evaluated several doses of once-weekly cagrilintide in adults with overweight or obesity without diabetes. It reported dose-dependent weight reduction compared with placebo, with gastrointestinal events as the most common adverse effects. The study was intended to identify doses for further development rather than to establish clinical efficacy. Combination data are reported in the CagriSema publications.

Combination with semaglutide (CagriSema)

Early-phase studies evaluated cagrilintide given together with semaglutide 2.4 mg, examining safety, tolerability and pharmacokinetics, and found greater weight reduction with the combination than with semaglutide alone in exploratory analyses. Phase 2 work in type 2 diabetes followed. These studies formed the basis for the REDEFINE phase 3 program, which evaluates the combination in people with obesity or overweight with and without type 2 diabetes.

Amylin biology

Cagrilintide is also of interest as a tool for studying amylin and calcitonin receptor pharmacology, including how long-acting analogues affect satiety circuits compared with short-acting pramlintide. Animal studies of amylin analogues have explored effects on food intake, gastric emptying and energy balance. Findings from animal and in-vitro models should be interpreted with care, given species differences in amylin receptor biology.

Regulatory status

Cagrilintide is investigational and not approved by the FDA or other major regulators, either alone or in combination with semaglutide. Check current status, as the CagriSema program has been in phase 3. Because it is not an approved drug or an established bulk drug substance, its use in pharmacy compounding is not supported; check current FDA guidance. For its status in sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A COA should confirm identity by mass spectrometry, with the observed mass matching the expected mass for the acylated peptide shown on this page, and report purity by reverse-phase HPLC. The disulfide bond should be confirmed as formed, since the reduced form differs by 2 Da, and the fatty acid side chain should be present and correctly attached. Amylin-family peptides are aggregation-prone, so size-exclusion chromatography or similar data on oligomers are valuable. Non-acylated peptide, deletion sequences and deamidation are other key impurities. Because the compound is investigational, pharmacopeial reference standards are not available. Endotoxin and net peptide content should be reported.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized cagrilintide sealed at -20 °C, protected from light and moisture. Although it was designed to aggregate less than native amylin, amylin analogues remain prone to fibril and oligomer formation in solution, influenced by pH, concentration, temperature and agitation. Reconstituted laboratory solutions should be refrigerated, handled gently, used promptly and aliquoted to avoid repeated freeze-thaw cycles. Avoid reducing agents that could break the disulfide bond.

Download the Cagrilintide data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• Semaglutide

  Semaglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. It is FDA-approved for type 2 diabetes (Ozempic, Rybelsus) and chronic weight management (Wegovy).

• Tirzepatide

  Tirzepatide is a once-weekly peptide that activates both the GIP and GLP-1 receptors. It is FDA-approved for type 2 diabetes (Mounjaro) and chronic weight management (Zepbound).

• Retatrutide

  Retatrutide is an investigational once-weekly peptide that activates the GIP, GLP-1 and glucagon receptors. It is not FDA-approved; Eli Lilly plans a BLA submission in Q1 2027 after phase 3 results.

References

1. PubMed: all indexed literature on Cagrilintide
2. ClinicalTrials.gov: registered studies mentioning Cagrilintide