What Amylin Is, and Why Novo Nordisk Paired It With Semaglutide in CagriSema

Most coverage of weight-management drugs focuses on GLP-1, but it is not the only gut-and-pancreas hormone involved in telling the brain a meal has happened. Amylin, a second peptide hormone, works through a different receptor family — and it is the basis of cagrilintide, the amylin analog Novo Nordisk combined with semaglutide in its investigational product CagriSema.

Amylin, also called islet amyloid polypeptide, is a 37-amino-acid peptide released by the same pancreatic beta cells that make insulin, and it is secreted alongside insulin after eating. According to recent reviews in the PMC literature, it slows gastric emptying, suppresses glucagon release after meals, and promotes fullness by acting on brainstem regions including the area postrema and the nucleus tractus solitarius.

Its receptors are unusual. Amylin receptors are built from the calcitonin receptor paired with one of three receptor activity-modifying proteins (RAMPs), producing three subtypes known as AMY1, AMY2, and AMY3. That is a separate system from the GLP-1 receptor, which is part of why researchers have looked at the two hormones as complementary rather than redundant. Receptor biology like this is studied across a wider peptide-research field focused on how peptides bind, fold, and aggregate. QSC Peptidology (qscpeptidology.com), an affiliate of this site, supplies research-grade peptides for laboratory use; those products are not prescription medicines and are not a substitute for an approved treatment.

Native amylin has a strong tendency to clump into amyloid fibrils and is cleared quickly, which makes it a difficult starting point for a medicine. An earlier analog, pramlintide, is approved in the U.S. as an add-on to mealtime insulin but is injected before meals because of its short duration. Cagrilintide was engineered for once-weekly dosing with structural changes and a fatty-acid attachment, a strategy broadly similar to the one used to extend semaglutide's half-life. A 2025 Nature Communications structural study reported that cagrilintide binds amylin receptors in an amylin-like way while also activating the calcitonin receptor.

REDEFINE 1, a 68-week phase 3a trial published in the New England Journal of Medicine in June 2025, randomized 3,417 adults with obesity, or overweight with a related condition, and without diabetes. Using the treatment-policy estimand, the investigators reported a mean body-weight change of −20.4% with cagrilintide–semaglutide versus −3.0% with placebo. Gastrointestinal adverse events affected 79.6% of the combination group and 39.9% of the placebo group, described as mainly transient and mild to moderate.

Novo Nordisk said it submitted a New Drug Application for CagriSema to the FDA in December 2025, and the company has stated that CagriSema is not approved in the U.S. or EU. A submission is a request for review, not an approval.

Amylin-based drugs are worth understanding because they target a second, distinct satiety pathway rather than simply being a stronger GLP-1. For now, CagriSema is investigational, and any product sold online as 'CagriSema' or 'cagrilintide' is not an approved version of it. Readers interested in where this class is heading should follow regulator announcements and peer-reviewed trial publications, and discuss any treatment decision with a licensed clinician.