• Despoina Vasilakou, Thomas Karagiannis, Eleni Athanasiadou, Maria Mainou, Aris Liakos, Eleni Bekiari, Maria Sarigianni, David R Matthews, and Apostolos Tsapas.
• Ann. Intern. Med. 2013 Aug 20; 159 (4): 262274262-74.

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs.PurposeTo assess the efficacy and safety of SGLT2 inhibitors in adults with type 2 diabetes.Data SourcesMEDLINE, EMBASE, and the Cochrane Library from inception through April 2013 without language restrictions; regulatory authorities' reports; and gray literature.Study SelectionRandomized trials comparing SGLT2 inhibitors with placebo or other medication for type 2 diabetes.Data ExtractionThree reviewers extracted or checked data for study characteristics, outcomes of interest, and risk of bias, and 3 reviewers summarized strength of evidence using the Grading of Recommendations Assessment, Development and Evaluation approach.Data SynthesisSodium-glucose cotransporter 2 inhibitors were compared with placebo in 45 studies (n = 11 232) and with active comparators in 13 studies (n = 5175). They had a favorable effect on hemoglobin A1c level (mean difference vs. placebo, -0.66% [95% CI, -0.73% to -0.58%]; mean difference vs. active comparators, -0.06% [CI, -0.18% to 0.05%]). Sensitivity analyses incorporating unpublished data showed similar effect estimates. Compared with other agents, SGLT2 inhibitors reduced body weight (mean difference, -1.80 kg [CI, -3.50 to -0.11 kg]) and systolic blood pressure (mean difference, -4.45 mm Hg [CI, -5.73 to -3.18 mm Hg]). Urinary and genital tract infections were more common with SGLT2 inhibitors (odds ratios, 1.42 [CI, 1.06 to 1.90] and 5.06 [CI, 3.44 to 7.45], respectively). Hypoglycemic risk was similar to that of other agents. Results for cardiovascular outcomes and death were inconclusive. An imbalance in incidence of bladder and breast cancer was noted with dapagliflozin compared with control.LimitationMost trials were rated as high risk of bias because of missing data and last-observation-carried-forward methods.ConclusionSodium-glucose cotransporter 2 inhibitors may improve short-term outcomes in adults with type 2 diabetes, but effects on long-term outcomes and safety are unclear.Primary Funding SourceNone.

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