CagriSema drives weight loss in rats by reducing energy intake and preserving energy expenditure

CagriSema is a combination of amylin (cagrilintide) and glucagon-like peptide-1 (semaglutide) analogues being developed for weight management. We quantified CagriSema’s action on energy intake and expenditure in rats. CagriSema caused 12% weight loss and a 39% reduction in food intake. In contrast, pair-feeding caused less weight loss while weight-matching required a 51% decrease in food intake. Approximately 1/3 of CagriSema’s weight loss efficacy was from an energy expenditure effect, blunting of metabolic adaptation, which is likely a hallmark of successful treatment of obesity. Bulk RNAseq of liver tissue collected from DIO rats after 20 days of CagriSema treatment or weight matched food restriction