Effects of Dipeptidyl Peptidase 4 Inhibitors and Sodium-Glucose Linked coTransporter-2 Inhibitors on cardiovascular events in patients with type 2 diabetes mellitus: A meta-analysis

Background Dipeptidyl Peptidase 4 Inhibitors (DPP4-I) and Sodium-Glucose Linked coTransporter-2 Inhibitors (SGLT2-I) improve glycemic control in patients with type 2 diabetes mellitus (DM). However, only few studies were designed to assess the efficacy and safety of these drugs on cardiovascular (CV) events and mortality. The purpose of the current study was to evaluate the effects of DPP4-Is and SGLT2-Is on CV events and mortality by meta-analysis. Methods Randomized trials enrolling more than 200 patients, comparing DPP-4-Is or SGLT2-Is versus placebo or active treatments in patients with DM, and reporting at least one event among all-cause and CV mortality, stroke, myocardial infarction (MI) and new onset of heart failure (HF), were included. Results 157 randomized trials (114 on DPP4-Is and 43 on SGLT2-Is) enrolling 140,470 patients (107,100 in DPP4-I and 33,370 in SGLT2-I studies) were included in the analysis. Compared to control, treatment with DPP4-Is did not affect all-cause (RR: 1.010; 95% CI: 0.935–1.091) and CV (RR: 0.975; CI: 0.887–1.073) mortality as well as risk of MI (RR: 0.915; CI: 0.835–1.002), stroke (RR: 0.933; CI: 0.820–1.062) and HF (RR: 1.083; CI: 0.973–1.205). Treatment with SGLT2-Is significantly reduced the risk of all-cause death by 28% (RR: 0.718; CI: 0.613–0.840), CV death by 33% (RR: 0.668; CI: 0.544–0.821), MI by 20% (RR: 0.803; CI: 0.668–0.965) and HF by 35% (RR: 0.652; CI: 0.517–0.823) without effect on stroke (RR: 1.158; CI: 0.912–1.469). Conclusions DPP4-Is show a safe CV profile as they do not affect mortality and CV events, including HF, in patients with type 2 DM. SGLT2-Is are associated with improved CV outcome and survival in DM patients.