Cardiorenal Protection: Potential of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes
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REVIEW
Cardiorenal Protection: Potential of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes Taichi Nagahisa
. Yoshifumi Saisho
Received: June 6, 2019 Ó The Author(s) 2019
ABSTRACT Recent large clinical trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, with the aim of verifying cardiovascular safety, have revealed that these medications have a preventative advantage on adverse cardiovascular outcomes, including worsening of heart failure and deterioration of nephropathy, in patients with type 2 diabetes (T2D). These observed benefits do not seem to correlate with the glucose-lowering effect, and the underlying mechanism is being intensively investigated. Given the results from recent studies, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend that patients with T2D and clinical cardiovascular disease (CVD) with inadequate glucose control despite treatment with metformin should receive an SGLT2 inhibitor or GLP-1 receptor agonist. In this review we summarize the results of recent cardiovascular outcome trials and discuss the potential Enhanced Digital Features To view enhanced digital features for this article go to https://doi.org/10.6084/ m9.figshare.9332171. T. Nagahisa Y. Saisho (&) Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan e-mail: [email protected]
clinical advantage of SGLT2 inhibitors and GLP1 receptor agonists. We also present practical implications of these glucose-lowering agents for reducing the risk of adverse cardiovascular events and progressive renal comorbidity in patients with T2D and CVD.
Keywords: Cardiovascular outcome; Glucagonlike peptide-1; Sodium-glucose cotransporter-2; Type 2 diabetes
INTRODUCTION Initial concerns about the cardiovascular safety of rosiglitazone [1], which were mostly dispelled following the analysis of data on cardiovascular outcomes in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycemia in Diabetes (RECORD) trial that assessed oral rosiglitazone combination therapy for patients with type 2 diabetes (T2D) [2], compelled the US Food and Drug Administration (FDA) to mandate that all new glucose-lowering agents must undergo post-marketing endpoint trials with the aim of verifying cardiovascular safety. In recent years, major clinical trials, including those on the cardiovascular safety of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors, have been published.
Diabetes Ther
Trials assessing the safety of DPP-4 inhibitors have reported a lack of superiority for major cardiovascular events compared with placebo [3–6] as well as an increase in the risk of hospitalization for heart failure, as seen with saxagliptin in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mel
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