Yaowen Wang, Xueting Hu, Xueying Liu, Zengqi Wang

We aimed to determine the effect of sodium glucose cotransporter 2 (SGLT2) inhibitor monotherapy on glycemic and other clinical laboratory parameters versus other antidiabetic medications or placebo therapy in patients with type 2 diabetes mellitus. In addition, we aimed to investigate the risk of diabetic ketoacidosis associated with SGLT2 inhibitor therapy and evaluate its weight-sparing ability. Meta-analysis. PubMed and MEDLINE were searched to identify eligible studies up to December 2015. Randomized controlled trials that assessed the efficacy and safety of SGLT2 inhibitor monotherapy versus placebo therapy or active control were considered. The Cochrane Collaboration Risk of Bias Tool was used to evaluate quality and bias. The mean difference was used to evaluate the glycemic and other clinical laboratory parameters for SGLT2 inhibitor intervention versus control by drugs or placebo. Similarly, the risk ratio was used to assess adverse events, and the I (2) was used to evaluate heterogeneity. SGLT2 inhibitors significantly decreased glycated hemoglobin (HbA1c) (P<0.001), weight (P<0.001), and the low-density lipoprotein/high-density lipoprotein ratio (P=0.03) compared with placebo therapy. No statistically significant changes were found in fasting plasma glucose, 2-hour postprandial glucose, or lipid parameters. Significant changes in the uric acid level were found for SGLT2 inhibitors versus placebo therapy (P=0.005) or active control (P<0.001). Although no significant change in levels of ketones occurred (P=0.93), patients receiving SGLT2 inhibitors were at greater risk of increased ketone bodies. Events suggestive of urinary tract infection and pollakiuria presented the greatest risk for patients receiving SGLT2 inhibitors versus active control or placebo therapy. SGLT2 inhibitors significantly decreased HbA1c, body weight, and the low-density lipoprotein/high-density lipoprotein ratio and were found to be safe and well tolerated in type 2 diabetes mellitus patients. Further randomized control trials are required to establish their risk for ketoacidosis.