Review ArticlesCardiovascular Safety and Benefits of Noninsulin Antihyperglycemic Drugs for the Treatment of Type 2 Diabetes Mellitus: Part 2Yandrapalli, Srikanth MD*; Malik, Aaqib MD*; Horblitt, Adam MD†; Pemmasani, Gayatri MBBS*; Aronow, Wilbert S. MD*; Frishman, William H. MD*Author Information From the *Department of Medicine and Division of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, NY †Division of Cardiology, Tulane Medical Center, New Orleans, LA. Disclosure: The authors have no conflicts of interest to report. Correspondence: Srikanth Yandrapalli, MD, Department of Cardiology, Westchester Medical Center, 100 Woods Road, Macy Pavilion Suite 100, Valhalla, NY 10595. E-mail: srikanth.yandrapalli@WMChealth.org. Cardiology in Review: September/October 2020 - Volume 28 - Issue 5 - p 219-235 doi: 10.1097/CRD.0000000000000311 Buy Metrics Abstract Ideal drugs to improve outcomes in type 2 diabetes mellitus (T2DM) are those with antiglycemic efficacy, as well as cardiovascular safety that has to be determined in appropriately designed cardiovascular outcome trials as mandated by regulatory agencies. The more recent antihyperglycemic medications have shown promise with regards to cardiovascular disease (CVD) risk reduction in T2DM patients at a high cardiovascular risk. Sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists are associated with better cardiovascular outcomes and mortality in T2DM patients than are dipeptidylpeptidase-4 inhibitors, leading to the Food and Drug Administration’s approval of empagliflozin to reduce mortality, and of liraglutide to reduce CVD risk in high-risk T2DM patients. For heart failure outcomes, sodium glucose cotransporter-2 inhibitors are beneficial, while glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors are neutral. Ongoing and planned randomized controlled trials of these newer drugs should clarify the possibility of class effects and of CVD risk reduction benefits in low–moderate cardiovascular risk patients. While we eagerly await the results on ongoing studies, these medications should be appropriately prescribed in T2DM patients with baseline CVD or those at a high CVD risk after carefully evaluating the elevated risk for adverse events like gastrointestinal disturbances, bladder cancer, genital infections, and amputations. Studies to understand the pleotropic and novel pathophysiological mechanisms demonstrated by the sodium glucose cotransporter-2 inhibitors will shed light on the effects of the modulation of microvascular, inflammatory, and thrombotic milieu for improving the CVD risk in T2DM patients. This is part 2 of the series on noninsulin antihyperglycemic drugs for the treatment of T2DM. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.