Synergistic combinations of gut-and-pancreas hormone-based therapies: Advancements in treatments for metabolic diseases.

Metabolic diseases, such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and liver disease, have become increasingly prevalent around the world. As an alternative to bariatric surgery, glucagon-like peptide 1 (GLP-1) receptor agonists have been at the forefront of weight-loss medication to combat these metabolic complications. Recently, there has been an exciting rapid emergence of new weight-loss medications that combine GLP-1 receptor (GLP-1R) agonists with other gut and pancreatic-derived hormones, like glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptor agonists. Dual agonist (GLP-1/GIP and GLP-1/GCG) and tri-agonist (GLP-1/GIP/GCG) administration generally result in greater weight loss, lower blood sugar and lipid levels, restoration of tissue function, and improvement in whole-body substrate metabolism compared to when GLP-1R agonists are used alone. The aim of this review is to summarize the recent literature of both preclinical and clinical studies on how these emerging gut-peptide therapies further improve weight loss and metabolic health outcomes for various metabolic diseases.