Sodium glucose co-transport 2 inhibitors in the treatment of type 2 diabetes mellitus: a meta-analysis of randomized double-blind controlled trials

Abstract

BackgroundThe discovery of sodium-glucose co-transporter 2 (SGLT2) inhibitors, with a novel mechanism independent of insulin secretion or sensitization, bring about a new therapeutic approach to the management of type 2 diabetes mellitus. The aim of this meta-analysis was to evaluate the safety and efficacy of SGLT2 inhibitors at different doses in randomized double blind clinical trials.MethodsThis meta-analysis was conducted by including randomized double-blind controlled trials of SGLT2 inhibitors in patients with type 2 diabetes irrespective of their antidiabetic drug exposure history but with an inadequate glycemic control. All the effect sizes were computed using the random effects model. Standardized mean differences (SMDs) and odds ratios (OR) were computed for continuous and dichotomous variables, respectively. Additional analyses like sensitivity analysis, subgroup analysis and meta-regression were also performed.ResultsThe pooled analyses demonstrated a significant reduction in mean changes in Hemoglobin A1c (HbA1c) (SMD = −0.78%, 95% CI, -0.87 to −0.69), fasting plasma glucose (FPG) (SMD = −0.70 mg/dl, 95% CI, -0.79 to −0.61), body weight (overall SMD = −0.59 kg, 95% CI, -0.65 to −0.52) and blood pressure from baseline with SGLT2 inhibitors based therapy. Consistently a significant number of patients treated with SGLT2 inhibitors achieved HbA1c < 7% (OR = 2.09, 95% CI, 1.77 to 2.46). SGLT2 inhibitors based therapy was associated with adverse events like genital and urinary tract infections.ConclusionAll studied doses of SGLT2 inhibitors, either as monotherapy or in combination with other antidiabetic agents, consistently improved glycemic control in patients with type 2 diabetes. However, a small percentage of patients suffer from genital and urinary tract infections.