Source of Cagrilintide

{{Infobox compound | name = Cagrilintide | subtitle = Investigational | Class = [[Amylin receptor agonist]] | Route = Subcutaneous, weekly | Status = Investigational; not approved alone | Combination = [[CagriSema]] with [[Semaglutide|semaglutide]] }} {{medical|talk=Investigational status}} '''Cagrilintide''' is a long-acting analogue of [[Amylin|amylin]], engineered to resist the aggregation that makes the native human sequence undevelopable and acylated for [[Albumin binding half-life extension|albumin binding]] so that weekly dosing is possible.{{r|lau2021}} Its actions follow those of amylin: slowed [[Gastric emptying|gastric emptying]], suppression of postprandial glucagon, and reduced food intake through hindbrain circuits distinct from the [[GLP-1 receptor|GLP-1]] pathway.{{r|hay2015}} It is studied principally in combination with [[Semaglutide|semaglutide]] as [[CagriSema]], on the rationale that the two satiety mechanisms are additive. It is not approved for use in any indication.{{r|lau2021}} == Design == The engineering problem is the same one pramlintide solved differently. Human amylin forms fibrils at concentrations well below those a formulation requires, so a developable analogue must break the β-sheet propensity of the central region while retaining receptor activity.{{r|hay2015}} Cagrilintide adds acylation to that, giving the long half-life the earlier mealtime analogue lacked. It engages the calcitonin receptor as well as the amylin receptor complexes, and whether that broader engagement contributes to or detracts from the effect is not established.{{r|lau2021}} Because the receptor family is unrelated to the incretin receptors, no single molecule can engage both; this is why the semaglutide combination is a co-formulation rather than a unimolecular dual agonist. See [[Dual incretin agonist]].{{r|hay2015}} == Reported findings == A phase 2 monotherapy trial reported approximately 10% weight reduction at 26 weeks. In combination with semaglutide the reported reduction exceeds that of either component alone; the combination programme is covered at [[CagriSema]].{{r|lau2021}} Gastrointestinal adverse events dominate, as with the incretin agonists, and are concentrated during escalation. Whether combining two agents that both delay gastric emptying compounds them is addressed only indirectly by the published designs.{{r|hay2015}} No cardiovascular or other outcome evidence exists for this compound.{{r|lau2021}} == Material sold under the name == Cagrilintide is offered by research-chemical suppliers. It is an unapproved investigational compound and this wiki does not represent it as suitable for human use; see [[Research use only]].{{r|reports}} Analytically it presents the difficulty common to amylin analogues: residual aggregation propensity means that size-based methods carry weight a [[Reverse-phase HPLC|reverse-phase]] purity determination cannot supply, since aggregates dissociate under reverse-phase conditions. See [[Peptide aggregation]].{{r|usp1503}} As with [[Retatrutide|retatrutide]], no marketed product means no generally available [[Reference standard|reference standard]], so identity rests on mass agreement with a calculated value.{{r|usp1503}} == References == {{reflist}} <ref name="lau2021">Lau DCW, Erichsen L, Francisco AM, et al. "Once-weekly cagrilintide for weight management in people with overweight and obesity." ''The Lancet'' 398(10317):2160–2172 (2021). PMID 34798060.</ref> <ref name="hay2015">Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. "Amylin: pharmacology, physiology, and clinical potential." ''Pharmacological Reviews'' 67(3):564–600 (2015). PMID 26071095.</ref> <ref name="usp1503">United States Pharmacopeia, General Chapter <1503>, ''Quality Attributes of Synthetic Peptide Drug Substances''.</ref> <ref name="reports">PeptidePedia Wiki community test-report tally, 2024–2026 (self-reported; see [[Project:Sourcing_guidelines]]).</ref> == See also == * [[Amylin]] * [[Amylin receptor agonist]] * [[CagriSema]] * [[Semaglutide]] * [[Peptide aggregation]] {{DEFAULTSORT:Cagrilintide}} [[Category:Amylin analogues]] [[Category:Peptide drugs]] [[Category:Articles describing unapproved compounds]]