Cagrilintide Research & Studies

The combination of cagrilintide and semaglutide has been shown in global studies to induce reductions in bodyweight. We assessed the efficacy and safety of a fixed-dose combination of cagrilintide 2·4 mg and semaglutide 2·4 mg versus semaglutide 2·4 mg for weight management in an east Asian population.

Amylin receptor agonists such as cagrilintide represent emerging obesity therapies. To understand mediators of cagrilintide action, we generated a transcriptomics atlas of over 530,000 cells comprising 80 neuronal cell populations across rat, mouse and macaque caudal brainstem, with spatial profiling to map distribution in the rat dorsal vagal complex (DVC). Here we show that cagrilintide regulates two conserved Calcr-expressing DVC neuronal populations. While acute cagrilintide treatment alters gene expression in area postrema Calcr/Ramp3 neurons, chemogenetic activation in rats fails to affect long-term food intake and body weight. In contrast, long-term cagrilintide treatment in rats upregulates prolactin-releasing hormone (Prlh) expression in nucleus of the solitary tract Calcr/Prlh cells that are conserved across rodents, macaques and humans. Knocking down DVC Prlh abrogates the effects of cagrilintide but not semaglutide in rats. Our study provides a cross-species spatially resolved atlas of DVC cell populations and defines Calcr/Prlh neurons as mediators of amylin receptor agonist action.

GIM/FP/GP: [Formula: see text].

Amylin (AmyR) and calcitonin (CTR) receptor co-agonists are currently in Phase II/III clinical trials for obesity treatment. Amylin binds to a heterodimeric receptor composed of CTR and the receptor activity modifying proteins 1, 2 or 3 (RAMP1-3).

Cagrilintide and semaglutide have each been shown to induce weight loss as monotherapies. Data are needed on the coadministration of cagrilintide and semaglutide (called CagriSema) for weight management in adults with type 2 diabetes, including those in a subgroup who are undergoing continuous glucose monitoring.

Despite the worldwide epidemic of obesity, there remain few approved pharmacological treatment options to bridge the gap between lifestyle therapy and bariatric surgery. Cagrilintide is an amylin-analog, now being developed in combination with the GLP-1 agonist semaglutide to achieve sustained weight loss in persons with overweight and obesity. Amylin, released with insulin from beta cells in the pancreas, induces its satiating effect via both the homoeostatic and hedonic regions of the brain. Semaglutide, a GLP-1 receptor agonist, reduces appetite via GLP-1 receptors in the hypothalamus and increases the production of insulin, and reduces glucagon secretion, delaying gastric emptying. These separate, but related mechanisms of action of an amylin-analog and a GLP-1 receptor agonist appear to have an additive effect on appetite reduction. Given the heterogeneity and complex pathogenesis of obesity, combination therapy with multiple pathophysiological targets is a logical approach to increasing weight loss response with pharmacotherapy. Cagrilintide alone, as well as cagrilintide in combination with semaglutide have shown promising weight loss in clinical trials that supports the further development of this therapy for sustained weight management.

The combination of cagrilintide and semaglutide (CagriSema) is being developed for the treatment of obesity and type 2 diabetes. The objective of this thorough QT study was to confirm that cagrilintide does not result in a clinically relevant prolongation in cardiac repolarization compared with placebo.

Novo Nordisk.

Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.

Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide is a long-acting amylin analogue under investigation for weight management. We assessed the dose-response relationship of cagrilintide regarding the effects on bodyweight, safety, and tolerability.