Review ArticlesCardiovascular 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 TrialsMalik, Aaqib H. MD, MPH*; Yandrapalli, Srikanth MD†; Goldberg, Michael MD‡; Jain, Diwakar MD†; Frishman, William H. MD†; Aronow, Wilbert S. MD†Author Information From the *Division of General Internal Medicine, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY †Division of Cardiology, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY ‡Division of Endocrinology, Department of Medicine, Westchester Medical Center, New York Medical College, Valhalla, NY. Disclosure: The authors have no conflicts of interest to report. Correspondence: Aaqib H. Malik, MD, MPH, Division of General Internal Medicine, Westchester Medical Center, 100 Woods Road, Valhalla, NY, 10595. E-mail: [email protected]. Cardiology in Review: May/June 2020 - Volume 28 - Issue 3 - p 116-124 doi: 10.1097/CRD.0000000000000265 Buy Metrics 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. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.