A novel approach to control hyperglycemia in type 2 diabetes: Sodium glucose co-transport (SGLT) inhibitors. Systematic review and meta-analysis of randomized trials

Background. Current treatment of hyperglycemia in type 2 diabetes (T2DM) is often ineffective and has unwanted effects. Therefore, novel antidiabetic drugs are under development. Objective. To assess efficacy and safety of the new antidiabetic drugs sodium glucose co-transport-2 (SGLT2) inhibitors in T2DM. Design and setting. Among 151 articles published on MEDLINE, Cochrane Library, EMBASE, PubMed, International meeting abstracts through December 2010, 13 randomized placebo-controlled trials (RCT) were included. Measurements. Two reviewers retrieved articles and evaluated study quality by appropriate scores. Main outcomes were pooled using random-or fixed-effects models. Results. Dapagliflozin significantly reduced HbA1c (weighted mean difference (WMD) -0.52%; 95% CI -0.46, -0.57%; P < 0.00001) fasting plasma glucose (WMD -18.28 mg/dL; 95% CI -20.66, -15.89; P < 0.00001), body mass index (WMD -1.17%; -1.41, -0.92%; P < 0.00001), systolic (WMD -4.08 mmHg; -4.91, -3.24), and diastolic (WMD -1.16 mmHg; -1.67, -0.66) blood pressure, and serum uric acid (WMD -41.50 mu mol/L; -47.22, -35.79). Other SGLT2 inhibitors showed similar results. Dapagliflozin treatment increased the risk of urinary (OR 1.34; 1.05-1.71) and genital (OR 3.57; 2.59-4.93) tract infection; it also mildly increased the risk of hypoglycemia (OR 1.27; 1.05-1.53) when co-administered with insulin. Limitations. Limitations of the literature include the small number, size, and duration of RCTs. Conclusions. Pending confirmation from larger RCTs, this analysis shows SGLT2 inhibitors are safe and effective for hyperglycemia treatment in T2DM.