Objective: Indirectly compare the efficacy and safety of ertugliflozin (ERTU) from the VERTIS SITA2 trial to other treatments in patients with inadequate A1C control on MET+DPP-4i.

Methods: Literature was searched up to end 2016 for RCTs in patients with A1C ≥7% on MET+DPP-4i. Included outcomes vs. placebo at 24-26 weeks were change in A1C, weight, systolic blood pressure, A1C <7%, urinary tract infections, genital mycotic infections, hypoglycemia and patients with ≥1 adverse event. Evidence synthesis used fixed effect and random effects Bayesian NMA, with model selection informed by guidelines. Credible intervals (CrI), analogous to 95% confidence intervals, were used to determine significance.

Results: Interventions compared (+background therapies) were dapagliflozin 10mg (MET+sitagliptin [SITA] and MET+saxagliptin), empagliflozin 10/25mg (MET+linagliptin), titrated canagliflozin (MET+SITA), titrated liraglutide (MET) and ERTU 5/15mg (MET+SITA). No relevant insulin RCTs were found. Added to MET+SITA, ERTU 5 and 15mg were significantly more effective than dapagliflozin 10mg (A1C mean difference [MD] 5mg -0.29%, CrI -0.56, -0.02; 15mg -0.37%, CrI -0.64, -0.10). Comparisons to other SGLT2i regimens did not find significant differences in A1C or other outcomes. The liraglutide arm of LIRA SWITCH discontinued SITA. Sensitivity analysis comparing triple therapy (MET+SITA+ERTU) vs. dual therapy (MET+liraglutide) did not find significant differences (A1C MD 5mg -0.07%, CrI -0.35, 0.22, 15mg -0.15% CrI -0.43, 0.14).

Conclusions: Amongst patients requiring triple therapy with SGLT2i added to MET+DPP-4i there was considerable heterogeneity between studies and assumptions of equivalence of background DPP-4i were required. Nonetheless, this analysis indicated that ERTU was more effective than dapagliflozin as add-on to MET+SITA and was comparable to other SGLT2i+MET+DPP-4i regimens.


A. McNeill: Employee; Self; Merck & Co., Inc.. Stock/Shareholder; Self; Merck & Co., Inc. G.M. Davies: Employee; 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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