Differential Effects of Thiazolidinediones and Dipeptidyl Peptidase-4 Inhibitors on Insulin Resistance and β-Cell Function in Type 2 Diabetes Mellitus: A Propensity Score-Matched Analysis

Abstract

Introduction: Comparisons of the glycemic durability between thiazolidinediones (TZDs) and dipeptidyl peptidase-4 (DPP-4) inhibitors remain insufficient. This study aimed to find clues for the differences in glycemic durability between TZDs and DPP-4 inhibitors by comparing the insulin resistance and β-cell function among patients using these agents. Methods: A total of 241 patients with type 2 diabetes mellitus (T2DM) treated with either pioglitazone (a TZD) or DPP-4 inhibitors as combination therapy with metformin for at least 1 year were analyzed. A propensity score based on the patients’ baseline characteristics and glycated hemoglobin (HbA1c) was used to match them. Indices for insulin resistance and secretory function of β-cells, namely the homeostasis model assessment of insulin resistance (HOMA-IR) or β-cells (HOMA-β), were calculated and compared. Multiple regression analysis was performed to find the independent variables correlated with β-cell function or insulin resistance. Results: Evaluation of the data from 168 matched patients with T2DM showed that TZD users had significantly better insulin sensitivity compared with DPP-4 inhibitor users (HOMA-IR 2.3 ± 1.9 vs. 3.5 ± 3.2, p = 0.003). Conversely, DPP-4 inhibitor users secreted more insulin than TZD users (HOMA-β 45.7 ± 31.6 vs. 61.4 ± 49.5, p = 0.016). Multiple linear regression analysis showed that these agents were independently associated with both insulin resistance and β-cell function. Conclusion: TZD users showed significantly better insulin sensitivity, whereas DPP-4 inhibitor users secreted more insulin from β-cells under similar glycemic control.