Post-meal β-cell function predicts the efficacy of glycemic control in patients with type 2 diabetes inadequately controlled by metformin monotherapy after addition of glibenclamide or acarbose

Background: This study aimed to explore parameters which will predict good control of HbA(1c) after adding a second anti-diabetic drug in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin monotherapy. Methods: Fifty-one patients (M/F: 25/26, mean age: 53.7 +/- 8.2 years, mean glycated hemoglobin [HbA(1c)] 8.4 +/- 1.2%) with T2DM inadequately controlled with metformin were randomized to add-on glibenclamide or acarbose for 16 weeks. Before and after combination therapy, the subjects underwent a 2-hour liquid mixed meal tolerance test to determine insulin secretion (HOMA beta, insulinogenic index, and disposition index [DI]) and insulin sensitivity (HOMA-IR and Matsuda insulin sensitivity index). Results: At baseline, there was a significant inverse relationship between DI120 and HbA(1c) (p = 0.001) in all subjects. The addition of glibenclamide and acarbose improved HbA1c significantly from 8.6 +/- 1.6% to 7.4 +/- 1.2% (p < 0.001), and from 8.2 +/- 0.8% to 7.5 +/- 0.8% (p < 0.001), respectively. In the glibenclamide group, DI120 significantly increased from 51.2 +/- 24.2 to 74.9 +/- 41.9 (p < 0.05), and in the acarbose group, from 62.5 +/- 31.4 to 91.7 +/- 36.2 (p < 0.05), respectively. Multiple regression analyses showed that both baseline HbA(1c) and DI120 independently predicted reduction of HbA1c as well as final HbA(1c) after combination therapy. Conclusions: In patients with T2DM inadequately controlled with metformin, add-on oral anti-diabetic agent with glibenclamide or acarbose resulted in the significant HbA(1c) reduction and improvement of beta-cell function. Subjects with greater baseline beta-cell function reserve displayed better glycemic response in the combination therapy of metformin with glibenclamide or acarbose.