Development of Cagrilintide, a Long-Acting Amylin Analogue.
Kruse. Thomas T; Hansen. Jakob Lerche JL; Dahl. Kirsten K; Schäffer. Lauge L; Sensfuss. Ulrich U; Poulsen. Christian C; Schlein. Morten M; Hansen. Ann Maria Kruse AMK; Jeppesen. Claus Bekker CB; Dornonville de la Cour. Charlotta C; Clausen. Trine Ryberg TR; Johansson. Eva E; Fulle. Simone S; Skyggebjerg. Rikke Bjerring RB; Raun. Kirsten K
Key Findings
- Cagrilintide is a lipid‑modified amylin analogue designed to avoid the amyloid‑forming problem of natural amylin.
- Its long‑acting formulation means fewer injections compared to pramlintide (which needs three daily shots).
- Clinical trials report significant weight loss when cagrilintide is used alone or together with semaglutide.
Practical Outcomes
- If approved, cagrilintide could become a convenient weekly (or less frequent) injection for weight loss and metabolic health, potentially enhancing the effects of existing GLP‑1 therapies. Biohackers and self‑experimenters may look for future protocols that combine it with semaglutide for synergistic fat loss, but should wait for full safety and dosing data from the trials.
Summary
Cagrilintide is a new, stable version of the hormone amylin that lasts a long time in the body, so it can be given less often than older drugs. Early trials show it helps people lose a lot of weight, either by itself or when combined with the popular GLP‑1 drug semaglutide.
Abstract
A hallmark of the pancreatic hormone amylin is its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug design effort. The amylin analogue pramlintide is commercially available for diabetes treatment as an adjunct to insulin therapy but requires three daily injections due to its short half-life. We report here the development of the stable, lipidated long-acting amylin analogue cagrilintide (<b>23</b>) and some of the structure-activity efforts that led to the selection of this analogue for clinical development with obesity as an indication. Cagrilintide is currently in clinical trial and has induced significant weight loss when dosed alone or in combination with the GLP-1 analogue semaglutide.
Study Information
pubmed
2021
2021-07-21T00:00:00.000Z
10.1021/acs.jmedchem.1c00565
85
40