Triple combination of insulin glargine, sitagliptin and metformin in type 2 diabetes: the EASIE post-hoc analysis and extension trial.

Aim: We examined the effects of adding glargine to metformin-sitagliptin (MS+G) or sitagliptin to metformin-glargine (MG+S) therapy in type 2 diabetic persons uncontrolled after 24-week MS or MG dual therapy.
Methods: Subjects with A1c≥7% on MS or MG treatment were respectively given glargine (0.2U/kg starting dose) or sitagliptin (100mg daily) for 12weeks. The primary endpoint was number of subjects attaining A1c goal defined as <7%.
Results: After receiving 24-week MS or MG dual therapy in the original EASIE Study, 42% (104/248) on MS and 68% (152/224) on MG attained A1c<7% (p<0.0001). The reduction in A1c was negatively associated with baseline fasting blood glucose (FBG) only in the MG group. Reduction in A1c was not related to baseline postprandial blood glucose (PPBG) in either the MG or MS group. Amongst 194 eligible patients, 57.7% (n=111) entered the 12-week extension trial [MS+G:74/131, 57.3%; MG+S:37/63, 58.7%) with 55 (51.9%) subjects attaining goal [MS+G:59.2%; MG+S:37.1%] at week 12. The final insulin dosage was similar in both groups [MS+G: 0.46U/kg; MG+S: 0.45U/kg] with a higher rate of hypoglycemia in the MG+S (6.5 events/patient-year) than the MS+G group (3.2 events/patient-year), although neither group had severe hypoglycemia.
Conclusion: In metformin-treated type 2 diabetes patients, high fasting BG predicted greater A1c reductions with the addition of glargine, but not with sitagliptin. In subjects uncontrolled with 6-month dual therapy of MS or MG, 50% attained A1c<7% with triple therapy of MS+G or MG+S in 12weeks. The increased rate of hypoglycemia with MG+S (but not with MS+G) underlines the need to take measures to avoid the hypoglycemia.
(Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)