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Diabetes Technol Ther. 2013 Mar;15(3):214-22. doi: 10.1089/dia.2012.0272. Epub 2013 Feb 21.

A randomized, double-blind, comparative therapy evaluating sitagliptin versus glibenclamide in type 2 diabetes patients already treated with pioglitazone and metformin: a 3-year study.

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  • 1Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.



This study evaluated if triple oral therapy can be useful in improving glycemic control compared with metformin monotherapy and with a metformin and pioglitazone combination. Furthermore, we also compared a triple metformin+pioglitazone+glibenclamide combination with a metformin+pioglitazone+sitagliptin one.


After a 2-year run-in therapy-augmenting phase with metformin and pioglitazone, 453 overweight, type 2 diabetes patients were randomized to 1 year of sitagliptin versus 1 year of glibenclamide to evaluate, as the primary outcome, the variation of β-cell function both in a fasting state and after an euglycemic hyperinsulinemic and hyperglycemic clamp. As secondary outcomes we evaluated glycemic control and insulin resistance.


Both the triple therapy combinations were more effective in reducing glycated hemoglobin compared with metformin monotherapy and with dual therapy metformin+pioglitazone. Fasting plasma insulin level and the homeostasis model assessment insulin resistance index were significantly increased by triple therapy with glibenclamide and decreased by the one with sitagliptin. Although sitagliptin did not change the homeostasis model assessment β-function index, this value was significantly increased by glibenclamide. The fasting plasma proinsulin level was decreased by sitagliptin. Triple therapy with sitagliptin greatly improved β-cell function measures compared with the glibenclamide one and also compared with metformin monotherapy and with the metformin+pioglitazone combination.


Dual combination therapy is more effective than monotherapy in improving glycemic control. When double therapy is not enough to reach an adequate glycemic control, sitagliptin should be preferred to glibenclamide as the third agent because of its positive effect on β-cells.

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