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. Here, we show that CagriSema blunts metabolic adaptation in rats. Quantifying CagriSema's action on energy intake and expenditure in rats we observe 12% weight loss with a 39% reduction in food intake. By contrast, pair-feeding causes less-pronounced weight loss, while weight matching requires a 51% decrease in food intake. Therefore, approximately one-third of CagriSema's weight loss efficacy arises from an effect on energy expenditure, the blunting of metabolic adaptation, which contributes to the successful treatment of obesity.