Systematic Review and Network Meta-analysis to Compare Dapagliflozin with other Diabetes Medications in Combination with Metformin for Adults with Type 2 Diabetes

Abstract

Objective: A network meta-analysis (NMA) update was undertaken to evaluate the sodium glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, versus other antidiabetes medications as add-on to metformin. This update allowed inclusion of a new drug class (glucagon-like peptide-1 [GLP-1] analogues), a new time point (24-weeks) and covariate analysis. Methods:The systematic review identified randomised controlled trials involving patients with type-2 diabetes mellitus (T2DM) inadequately controlled on metformin. Comparators included dipeptidyl peptidase-4 inhibitors (DPP-4i), thiazolidinediones (TZDs), GLP-1s, sulfonylureas (SUs) and dapagliflozin. Bayesian NMA was conducted at 24-and 52-weeks for mean change in HbA1c, systolic blood pressure (SBP), weight, and proportion of patients experiencing hypoglycaemia. Results:The systematic review identified 2247 articles, of which 16were eligible for inclusion. Combined with 19 studies frompre-2011 analysis, a total of 19 and 8 studies were included in the 24-week and 52-week NMA, respectively. There were no significant differences in HbA1c or SBP between dapagliflozin and other classes, including GLP-1s, at either time point. Significant results were seen for weight loss by 24-weeks for dapagliflozin versusDPP-4i (-2.24 kg [95% CI -3.25,-1.24]) and TZDs (-4.65 kg [-5.89,-3.45]), and at 52-weeks versus SUs, DPP-4i and TZDs. Dapagliflozin also resulted in significantly lower hypoglycaemia risk versus SU (OR: 0.05 [0.01,0.19]) over 52-weeks. Conclusions:This NMA update supports previous findings that effects on HbA1c are similar between drug classes and that dapagliflozin plus metformin offers superior weight control for T2DM patients compared with many other agents. The wider evidence base compared to previous analysis increases the confidence in the results.