SGLT2 Inhibitors May Predispose to Ketoacidosis

作者：Simeon I. Taylor, Jenny E. Blau, Kristina I. Rother · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2015 · DOI：10.1210/jc.2015-1884 · 被引用次数：559 · 研究领域：Diabetes Treatment and Management、Pancreatic function and diabetes、Cardiovascular Function and Risk Factors

CONTEXT: Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs that increase urinary excretion of glucose, thereby improving glycemic control and promoting weight loss. Since approval of the first-in-class drug in 2013, data have emerged suggesting that these drugs increase the risk of diabetic ketoacidosis. In May 2015, the Food and Drug Administration issued a warning that SGLT2 inhibitors may lead to ketoacidosis. EVIDENCE ACQUISITION: Using PubMed and Google, we conducted Boolean searches including terms related to ketone bodies or ketoacidosis with terms for SGLT2 inhibitors or phlorizin. Priority was assigned to publications that shed light on molecular mechanisms whereby SGLT2 inhibitors could affect ketone body metabolism. EVIDENCE SYNTHESIS: SGLT2 inhibitors trigger multiple mechanisms that could predispose to diabetic ketoacidosis. When SGLT2 inhibitors are combined with insulin, it is often necessary to decrease the insulin dose to avoid hypoglycemia. The lower dose of insulin may be insufficient to suppress lipolysis and ketogenesis. Furthermore, SGLT2 is expressed in pancreatic α-cells, and SGLT2 inhibitors promote glucagon secretion. Finally, phlorizin, a nonselective inhibitor of SGLT family transporters decreases urinary excretion of ketone bodies. A decrease in the renal clearance of ketone bodies could also increase the plasma ketone body levels. CONCLUSIONS: Based on the physiology of SGLT2 and the pharmacology of SGLT2 inhibitors, there ...