The Beneficial Effects of Combination Therapy With SGLT-2 Inhibitors and GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus is a chronic metabolic disorder associated with microvascular and macrovascular complications. Hyperglycemia and insulin resistance are core pathophysiological components of diabetes, linked to subclinical inflammation and persistent oxidative stress, which result in endothelial dysfunction and subsequent atherogenesis. Nowadays, several arrows in the diabetologist's quiver are available for the management of diabetes, providing flexibility and the ability to adopt a personalized approach tailored to each patient's needs. Two of the most commonly prescribed antidiabetic drugs are sodium-glucose cotransporter 2 inhibitors and glucagon- like peptide-1 receptor agonists. Both agents are associated with beneficial metabolic, cardioand nephro-protective effects independent of their antidiabetic properties; thus, their indications have and are continuously expanding over and beyond the treatment of diabetes. Given that these two drug classes have different mechanisms of action, the use of their combination achieves a synergistic interaction and confers additional benefits. The aim of this review is to provide a summary of current knowledge regarding the use of these two drug classes, shed light on the available evidence on their combination, and discuss future perspectives on optimal therapeutic decisions in clinical practice. Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in combination therapy are a promising therapeutic duo and are expected to influence future guidelines and decision-making in everyday clinical practice.