SGLT2i Dual Therapy with Metformin (Met) for Type 2 Diabetes Mellitus (T2DM)—Systematic Literature Review and Network Meta-analysis (NMA)
Abstract
Objective: Indirectly compare the efficacy and safety of ertugliflozin (ertu) from the VERTIS MET and FACTORIAL trials to other SGLT2i as an add-on to MET. Methods: Pubmed, EMBASE and Cochrane databases were searched through to end 2016 for RCTs of 24-26 weeks duration in T2DM patients with uncontrolled A1C on MET. Comparators to ertu 5mg and 15mg were low and high doses of SGLT2i licensed in Europe and USA: canagliflozin (cana), dapagliflozin (dapa) and empagliflozin (empa). Included outcomes vs. placebo at 24-26 weeks were change in A1C, weight, systolic blood pressure (SBP), A1C <7% and safety outcomes (urinary tract infections [UTIs], genital mycotic infections [GMIs], hypoglycemic events and patients with ≥1 adverse event [AE]). Evidence synthesis used both fixed effect (FE) and random effects (RE) Bayesian NMA, with model selection informed by guidelines. Credible intervals (CrI), analogous to 95% confidence intervals, were used to determine significance. Results: The NMA included 7 RCTs. Ertu was significantly more effective in reducing A1C than dapa doses (ertu 5mg vs. dapa 5mg mean difference (MD): -0.22%, CrI -0.42, -0.02; ertu 15mg vs. dapa 10mg MD:-0.26%, CrI -0.46, -0.06) and ertu 15mg was superior to empa 25mg (MD: -0.23%, CrI -0.44, -0.03). There were no further significant differences between ertu and other SGLT2i for change in A1C, SBP, weight, A1C <7%, UTIs or ≥1 AEs. Limited number of hypoglycemic and GMI events in placebo comparators resulted in…
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