Cagrilintide — the long-acting amylin analog, explained

Cagrilintide is a synthetic, acylated analog of human amylin (islet amyloid polypeptide, IAPP) designed for once-weekly research dosing. It was developed by Novo Nordisk and has emerged as one of the most-studied amylin agonists in the current metabolic-research pipeline — most notably in combination with semaglutide ('CagriSema'), where dual engagement of the GLP-1 and amylin pathways has shown additive research-model effects on satiety signaling and body-mass endpoints. This primer covers the molecule, the amylin-receptor biology, the published literature base, the CagriSema combination rationale, and research-context framing.

The molecule. Cagrilintide is a 37-amino-acid analog of human amylin. It differs from native amylin at multiple residues — critically at Lys14, where a C18 fatty acid (octadecanedioic acid) is attached via a γ-Glu-2×OEG linker. This acylation enables non-covalent binding to serum albumin, extending the in-vivo half-life to approximately 7 days and enabling once-weekly research dosing. Molecular weight is approximately 4,400 Da. The peptide is amidated at the C-terminus, matching native amylin, and retains the disulfide bond between Cys2 and Cys7 that stabilizes the N-terminal structure required for receptor binding. Cagrilintide is structurally distinct from pramlintide (Symlin, approved 2005), an earlier amylin analog with three proline substitutions preventing aggregation but lacking acylation — pramlintide has a 50-minute half-life vs. cagrilintide's ~7 days.

The amylin receptor family. Amylin is a 37-residue peptide hormone co-secreted with insulin by pancreatic β-cells in response to food intake. Its receptor is not a single entity but a family of complexes — the calcitonin receptor (CTR) heterodimerized with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3), yielding AMY1, AMY2, and AMY3 respectively. Amylin's main characterized effects are (1) slowing of gastric emptying, (2) suppression of post-prandial glucagon secretion, and (3) central satiety signaling via the area postrema and other brainstem/hypothalamic circuits. Cagrilintide engages the full amylin receptor family and retains substantial native calcitonin-receptor activity, which has been proposed as contributing to its extended satiety profile in research models.

Published literature — primary sources. The foundational pharmaceutical-chemistry paper is Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, Schlein M, Raun K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021;64(15):11183-11194 (doi: 10.1021/acs.jmedchem.1c00565) — describes the molecule's design, fatty-acid selection, and receptor-binding profile. The principal Phase 2 monotherapy trial is Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino D, Batterham RL. 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 (doi: 10.1016/S0140-6736(21)01751-7) — 706 adults, dose-response from 0.3 to 4.5 mg weekly. For the CagriSema combination rationale: Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Lau DCW. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748 (doi: 10.1016/S0140-6736(21)00845-X).

The CagriSema research rationale. The scientific case for combining cagrilintide with semaglutide rests on pathway orthogonality. GLP-1 receptor agonism (semaglutide) and amylin receptor agonism (cagrilintide) act through distinct central and peripheral satiety circuits — GLP-1 agonism acts prominently at the dorsomedial hypothalamus, nucleus of the solitary tract, and area postrema; amylin acts at the area postrema via a distinct receptor population. Combined engagement increases satiety signaling without requiring higher doses of either agonist, which has implications for both efficacy and tolerability. The Enebo 2021 trial showed combined cagrilintide 2.4 mg + semaglutide 2.4 mg produced body-mass reductions numerically larger than either agent alone at 20 weeks. The Phase 3 REDEFINE program (REDEFINE-1 in a body-composition cohort, REDEFINE-2 in a glycemic-dysregulation cohort, REDEFINE-3 cardiovascular outcomes) is the definitive test of whether additive behavior translates to long-term endpoints; topline data started reading out in 2024-2025.

Administration routes and dose ranges. Published cagrilintide research uses subcutaneous injection exclusively. Once-weekly dosing is the standard. Phase 2 monotherapy spanned 0.3, 0.6, 1.2, 2.4, and 4.5 mg weekly with dose-proportional body-mass effects. CagriSema Phase 1b used cagrilintide 0.16, 0.30, 0.60, 1.2, or 2.4 mg weekly paired with semaglutide 2.4 mg weekly. Titration (gradually increasing dose every 4 weeks) is used to manage early-dose gastrointestinal effects, which are the dose-limiting tolerability issue in all published trials to date.

Storage and handling. Cagrilintide is stable refrigerated (2-8 °C). Protect from light. Do not freeze — the C18 acylation is stable but tertiary structure can be affected by freeze-thaw. In-use stability at room temperature is approximately 28 days, matching the clinical pen convention used for other acylated peptides (semaglutide, tirzepatide). Vivaprime ships cagrilintide at 10 mg/mL in a prefilled 3 mL pen, which avoids the reconstitution, vialing, and aliquoting steps that historically created handling variability in amylin-analog work.

What the COA should say. A batch-specific COA for cagrilintide should include (1) identity by HPLC-MS matching the theoretical mass (~4,400 Da for the amidated C-terminal form, which is the correct biologically-active form), (2) purity by reverse-phase HPLC ≥ 98% with an impurity profile dominated by known des-amido and oxidation variants, (3) endotoxin by LAL in EU/mg — recombinant-expressed cagrilintide has a well-characterized endotoxin profile, (4) water content by Karl Fischer if lyophilized. The production route (solid-phase synthesis vs. recombinant) should be disclosed.

Research-use only. Vivaprime supplies cagrilintide as research reference material for qualified researchers engaged in in-vitro and research-context work. Cagrilintide has not been approved by the FDA for any therapeutic indication and is under active Phase 3 investigation in the CagriSema program. Nothing on this page constitutes a therapeutic, diagnostic, or consumption recommendation. Purchasers affirm the research-use agreement at checkout. Related research primers: [semaglutide](/blog/semaglutide-research-primer), [tirzepatide](/blog/tirzepatide-research-primer), [retatrutide](/blog/retatrutide-research-primer).