Therapeutic potential of relaxin or relaxin mimetics in managing cardiovascular complications of diabetes

Diabetes mellitus is a metabolic disease with an escalating global prevalence. Despite the abundance and relative efficacies of current therapeutic approaches, they primarily focus on attaining the intended glycaemic targets, but patients ultimately still suffer from various diabetes-associated complications such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis. There is a need to explore innovative and effective diabetic treatment strategies that not only address the condition itself but also combat its complications. One promising option is the reproductive hormone relaxin, an endogenous ligand of the RXFP1 receptor. Relaxin is known to exert beneficial actions on the cardiovascular system through its vasoprotective, anti-inflammatory and anti-fibrotic effects. Nevertheless, the native relaxin peptide exhibits a short biological half-life, limiting its therapeutic potential. Recently, several relaxin mimetics and innovative delivery technologies have been developed to extend its biological half-life and efficacy. The current review provides a comprehensive landscape of the cardiovascular effects of relaxin, focusing on its potential therapeutic applications in managing complications associated with diabetes. The latest advancements in the development of relaxin mimetics and delivery methods for the treatment of cardiometabolic disorders are also discussed.