Cagrilintide and Amylin Analogs
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Amylin analogs are the next incretin-adjacent class. Pramlintide is the only approved amylin analog, dosed at mealtimes; cagrilintide is a long-acting, once-weekly investigational analog developed in combination with semaglutide as CagriSema, which Novo Nordisk has filed with FDA for weight management.
Amylin biology
Amylin is a 37-amino-acid peptide co-secreted with insulin by pancreatic beta cells. It slows gastric emptying, suppresses postprandial glucagon and signals satiety through the area postrema. Native human amylin aggregates into amyloid fibrils, which makes it unsuitable as a drug. Pramlintide replaces three residues with prolines from rat amylin to prevent aggregation. Cagrilintide is an acylated, non-selective amylin and calcitonin receptor agonist with a half-life of about one week. The calcitonin receptor activity is thought to add to its effect on appetite.
Regulatory status
Pramlintide (Symlin) was approved by FDA in 2005 as mealtime adjunct therapy for type 1 and type 2 diabetes in insulin users. Cagrilintide is investigational. In the REDEFINE 1 phase 3 trial, CagriSema produced greater weight reduction than either component alone, and Novo Nordisk has submitted it for FDA review. Amycretin, a single molecule combining GLP-1 and amylin agonism, is in clinical development in oral and injectable forms. Unapproved peptides fall under WADA S0.
Delivery profile
Cagrilintide is given by weekly subcutaneous injection. Its acylation extends half-life, but the peptide still carries amylin's tendency toward aggregation under stress, and co-formulation with semaglutide requires compatible pH and excipients in one pen. Oral delivery faces the full set of peptide barriers, and the amycretin oral program uses permeation enhancer technology similar to oral semaglutide. Pramlintide cannot be mixed with insulin in the same syringe because of pH incompatibility.
What this means for delivery research
Amylin analogs combine peptide stability questions (fibrillation) with the usual oral barriers, making them a demanding test for any encapsulation approach. Stress testing for fibril formation (agitation, temperature, interfaces) is therefore an essential first step for any encapsulated amylin analog, before release rate or bioavailability are considered. Thioflavin T assays and size-exclusion chromatography are standard methods. Co-delivery with a GLP-1 agonist adds compatibility testing between two peptides in one system.
Key facts
- Cagrilintide has a half-life of about 7 to 8 days and was studied with semaglutide in a phase 1b trial (Enebo et al. 2021, Lancet 397:1736)
- In REDEFINE 1, CagriSema produced mean weight reduction of 20.4% at 68 weeks versus 3.0% with placebo (Garvey et al. 2025, N Engl J Med)
- Pramlintide was approved by FDA as mealtime adjunct therapy in insulin-using patients with diabetes (FDA label, Symlin 2005)
- Novo Nordisk has filed CagriSema with FDA for weight management (Novo Nordisk company announcement, December 2025)
How our delivery technology applies
For amylin analogs, encapsulation has a stability role before it has a bioavailability role. A peptide held in a hydrated inner core, separated by biopolymer layers from interfaces and co-formulated actives, is less exposed to the surface-driven aggregation that affects amylin sequences. For partners, we would test fibrillation under stress alongside release and protease resistance.
Test aggregation-resistant peptide formats with Vegalab's feasibility program.