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ClinicalOnce-weekly amylin analogue for weight loss

Cagrilintide

Also indexed as AM833, Cagri, Long-acting amylin analogue

Cagrilintide is a long-acting acylated amylin analogue developed by Novo Nordisk for the treatment of obesity and type 2 diabetes. It mimics the pancreatic hormone amylin to reduce appetite, slow gastric emptying, and promote satiety. In clinical trials, it has been studied both as a monotherapy and in combination with semaglutide (as CagriSema), demonstrating meaningful and sustained body weight reduction.

Overview

Following subcutaneous injection, cagrilintide undergoes slow absorption (Tmax ~2–3 days) with high plasma protein binding via fatty acid–albumin interactions, achieving steady-state concentrations after approximately 4 weeks of weekly dosing. It crosses a limited blood-brain barrier at circumventricular organs (area postrema lacks a tight blood-brain barrier), engaging AMY receptors to: (1) inhibit glucagon secretion from pancreatic alpha-cells; (2) delay gastric emptying via vagal efferent modulation; (3) reduce hypothalamic NPY/AgRP neuropeptide expression; and (4) potentiate GLP-1 receptor signalling when co-administered, producing additive to synergistic weight-loss effects in CagriSema trials.

Proposed mechanism

Cagrilintide binds to amylin receptors (AMY1R, AMY2R, AMY3R), which are heterodimers of the calcitonin receptor and receptor activity-modifying proteins (RAMPs 1, 2, or 3), activating cAMP-mediated signaling pathways in the hypothalamus, area postrema, and nucleus of the solitary tract. This activation suppresses glucagon secretion, slows gastric emptying, and reduces food intake by enhancing central satiety signaling. The fatty acid acylation of cagrilintide extends its half-life to approximately 7 days, enabling once-weekly subcutaneous dosing.

What the evidence supports

Randomised controlled trial data in humans exists and supports use in specific contexts.

Graded Clinical

Findings supported by randomised, controlled trials in humans, with pre-registered endpoints and published results.

Key citations

Representative primary sources, including results that did not favour the compound.

  1. [1]

    Cagrilintide at 4·5 mg for once-weekly subcutaneous treatment of type 2 diabetes (SCALE CAMBER): a double-blind, randomised, placebo-controlled, dose-finding trial

    · The Lancet Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00318-6 · 2021

  2. [2]

    CagriSema versus semaglutide, cagrilintide and placebo in participants with obesity: REDEFINE 1

    · Novo Nordisk pipeline disclosure; ClinicalTrials.gov NCT04982575 · 2024

  3. [3]

    Amylin receptor pharmacology and therapeutic potential

    · British Journal of Pharmacology — review of CTR/RAMP signalling · 2020

Citation records in this build are illustrative placeholders for the design.

Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.

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