Concomitant glucose-dependent insulinotropic receptor (GIPR) and glucagon-like peptide-1 receptor (GLP1R) agonism stimulates TG-rich lipoprotein metabolism and attenuates atherosclerosis development

Abstract

Background and Aims: Tirzepatide, a dual GIP/GLP-1 receptor agonist, was recently shown to cause robust weight loss in patients with Type II Diabetes (Frias et al. 2018). Since GIPR agonism stimulates lipolysis in white adipose tissue and GLP1R agonism promotes brown adipose tissue (BAT) thermogenesis, we hypothesized that combining GIPR and GLP1R agonism enhances the fatty acid (FA) flux to BAT to facilitate thermogenesis, thereby alleviating dyslipidemia and atherosclerosis development.