Cardiovascular Outcomes With the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes and Chronic Kidney Disease

An Updated Meta-Analysis of Randomized Controlled Trials

Abstract

Diabetes mellitus (DM) and chronic kidney disease (CKD) significantly increase the risk of cardiovascular morbidity and mortality. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a new class of hypoglycemic agents that have shown significant promise in the reduction of cardiovascular events. Current guideline recommendations do not support the use of these agents in patients with CKD stage 3 or higher. We performed a comprehensive meta-analysis to evaluate their cardiovascular effects in patients with type 2 DM and CKD stage 3 or higher. A comprehensive search was performed in PubMed, Cochrane central, and Embase. Software R was utilized to perform a meta-analysis via the generic inverse variance method. Additionally, we conducted a network meta-analysis to compare the relative efficacy and safety of each agent. Data from 7 randomized controlled trials and 6527 participants were available. In patients with type 2 DM and CKD, SGLT-2 inhibitor use resulted in a significant relative risk reduction of myocardial infarction (22%), heart failure hospitalization (39%), and major adverse cardiac events (20%) (all P-value < 0.05). There was also a trend towards a reduction in stroke and cardiovascular mortality. In a network meta-analysis, canagliflozin was the most effective in reducing myocardial infarction, stroke, and heart failure hospitalization. Empagliflozin performed better for the outcome of cardiovascular mortality, but the results failed to reach significance. In conclusion, SGLT-2 inhibitors significantly improve cardiovascular outcomes in patients with type 2 DM and CKD stage 3 or higher, providing a compelling reason for their use in this population subgroup.