Objective:Indirectly compare the efficacy and safety of ertugliflozin (ertu) from the VERTIS MONO trial to other SGLT2i when used as monotherapy.

Methods: Pubmed, EMBASE and Cochrane were searched through to end of 2016 for RCTs of 24-26 weeks duration in T2DM patients with uncontrolled A1C on no anti-hyperglycemic therapy. 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 loss (WL), systolic (SBP), A1C <7%, urinary and genital mycotic infections, hypoglycemia and patients with ≥1 adverse event (AE). Evidence was synthesized using 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 10 RCTs with FE models selected for all analyses except A1C <7% and WL. For change in A1C ertu 15mg was significantly more effective vs. dapa 10mg (mean difference (MD): -0.36%, CrI -0.65, -0.08) and empa 25mg (MD:-0.31%, CrI -0.58, -0.04). There were no other significant differences for efficacy outcomes between ertu and other SGLT2i, except a larger reduction in SBP for cana 300mg vs. ertu 15mg (MD: 3.45 mmHg, CrI 0.15, 6.76). Analyses of safety outcomes did not identify any significant differences or could not be interpreted due to scarcity of events in placebo arms preventing network convergence. The impact of inter-trial heterogeneity was tested, but remains a potential confounder.

Conclusions: In an indirect comparison ertu 5mg was comparable to other low dose SGLT2i at reducing A1C whereas ertu 15mg was more effective vs. dapa 10mg and empa 25mg. With the exception of SBP for ertu 15mg vs. cana 300mg, remaining outcomes were comparable to other SGLT2i for both ertu 5mg and 15mg.


G.M. Davies: Employee; Self; Merck & Co., Inc. A. McNeill: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. E. Kruger: Employee; Self; QuintilesIMS. S.L. Kowal: None. F. Ejzykowicz: Employee; Self; Merck Sharp & Dohme Corp. H. Hannachi: Employee; Self; Merck & Co., Inc. N.B. Cater: Employee; Self; Peter Sheehan Diabetes Care Foundation, Inc. E. McLeod: Employee; Self; Pfizer Inc..

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