Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care

Abstract

The available data suggest differences in the course of type 2 diabetes mellitus (T2DM) between men and women, influenced by the distinguishing features of the sex. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are a relatively new class of antidiabetic drugs that act by mimicking the function of endogenous glucagon-like peptide 1. They constitute valuable agents for the management of T2DM as, in addition to exerting a strong hypoglycemic action, they present cardiorenal protective properties, promote weight loss, and have a good safety profile, particularly with respect to the risk of hypoglycemia. Due to the precedent of studies having identified sexual dimorphic elements regarding the action of other antidiabetic agents, ongoing research has attempted to examine whether this is also the case for GLP-1 RAs. Until now, sex differences have been observed in the impact of GLP1-RAs on glycemic control, weight reduction, and frequency of adverse events. On the contrary, the question of whether these drugs differentially affect the two sexes with respect to cardiovascular risk and incidence of major adverse cardiovascular events remains under investigation. Knowledge of the potential sex-specific effects of these medications is extremely useful for the implementation of individualized therapeutic plans in the treatment of T2DM. This narrative review aims to present the available data regarding the sex-specific action of GLP-1 RAs as well as to discuss the potential pathophysiologic mechanisms explaining these dissimilarities.