Pharmacologic strategies to reduce cardiovascular disease in type 2 diabetes mellitus: focus on SGLT-2 inhibitors and GLP-1 receptor agonists

Patients with type 2 diabetes mellitus (T2D) present an increased risk for cardiovascular (CV) complications. In addition to improvement in glycaemic control, glucose-lowering therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-dependent glucose cotransporter (SGLT)-2 inhibitors, have been shown to significantly reduce CV events. In 2008, the US Food and Drug Administration mandated that all new glucose-lowering drugs undergo CV outcomes trials (CVOTs) to determine their CV safety. These trials have largely demonstrated no major CV safety concerns. Most notably, the GLP-1RAs and SGLT-2 inhibitors have been found to be not only safe, but also cardioprotective compared to placebo. The SGLT-2 inhibitors have opened a new perspective for clinicians treating patients with T2D and established CV disease in light of their ‘pleiotropic’ effects, specifically on heart failure, while GLP-1RAs seem to present more favourable effects on atherosclerotic events. In this review, we discuss the role of GLP-1RAs and SGLT-2 inhibitors to reduce CV risk in T2D patients and suggest an individualized therapeutic approach in this population based on the presence of metabolic and CV comorbidities.