Dual incretin agonism in the treatment of Type 2 Diabetes and Obesity

Type 2 diabetes (T2DM) is the fastest-growing chronic disease in Australia and is strongly associated with obesity, a well-established risk factor for T2DM. Incretin-based therapeutics are promising new treatments for T2DM and obesity due to their glucose-lowering and weight-loss effects, through actions mediated by the glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR). An emerging pharmacological approach involves simultaneous targeting of both GLP-1R and GIPR to leverage the actions of both incretin hormones. The thesis presents new mechanistic insights into these dual incretin (GLP-1R/GIPR) agonists and elucidates the impact of modulating each receptor on metabolic homeostasis.