The Rise of GLP-1 Agonists: The Paradigm-shifting Frontier in Diabetic Kidney Disease, Cardio-renal Protection and Beyond

Abstract

GLP 1 agonists have evolved into one of the most potent weapons in the arsenal to tackle diabetes and metabolic disease, while providing significant cardiorenal outcomes, as cemented by the FLOW trial. Their pleiotropic action extends into spheres of immune regulation, alleviation of autophagy and pyroptosis, in addition to their multi-organ action encompassing diabetic control and weight reduction. The fact that their potential extends beyond the frontiers of diabetes or chronic kidney disease into realms of neuroprotection, musculoskeletal disorders and metabolic dysfunction-associated steatohepatitis (MASH), obstructive sleep apnoea, amongst several other disorders provides promising prospects that make this molecule a literal shapeshifting all-rounder in Medicine. This review aims to trace the journey of this multifaceted drug, while exploring evidence regarding its therapeutic applications, particularly diabetes, weight loss management, and cardiorenal outcomes; evidence from clinical trials, highlighting practical considerations, major challenges and roadblocks in their use, dual and triple GLP-1 agonists in development as well as the future horizons of GLP-1 agonists.