Alogliptin: a DPP-4 Inhibitor Modulating Adipose Tissue Insulin Resistance and Atherogenic Lipid

Aims: The purpose of this study is to investigate the regulation of adipose tissue insulin resistance with DPP-4 inhibitors in treatment-naive subjects with T2DM and to examine its relation to other diabetic parameters.

Subjects And Methods: A total of 147 subjects were treated with alogliptin 12.5-25 mg/day (n = 55), sitagliptin 25-50 mg/day (n = 49), or teneligliptin 10-20 mg/day (n = 43) monotherapy for 3 months. Changes in adipo-IR, a mathematical model used to evaluate adipose tissue insulin resistance, and various diabetic parameters were analyzed in this prospective, non-randomized observational study.

Results: Among these three drugs, only alogliptin significantly reduced adipo-IR (-25.9%, p < 0.004) and some lipid parameters, such as LDL-C, T-C/HDL-C, log(TG)/HDL-C, non-HDL-C/HDL-C, and LDL-C/HDL-C. Subjects in the alogliptin group were divided into two groups with distinct changes in adipo-IR. Group A had a significant decrease in adipo-IR (-56.5%, p < 0.00001, n = 28), whereas group B had an insignificant increase (19.1%, p = 0.055, n = 27). Significant reductions in FBG or HbA1c were observed in groups A and B, respectively. Group A also showed significant reductions in HOMA-R, T-C/HDL-C, TG, log(TG)/HDL-C, non-HDL-C/HDL-C, LDL-C/HDL-C, and FFA, as well as increases in QUICKI or HDL-C. In contrast, group B showed significant reductions in QUICKI or LDL-C, and increases in HOMA-R, insulin, HOMA-B, C-peptide, or CPR-index.

Conclusions: In contrast to other tested DPP-4 inhibitors, alogliptin demonstrated the ability to down-regulate insulin resistance in adipose tissue, as well as certain atherogenic lipids. This study provides the initial evidence of a DPP-4 inhibitor's potential to regulate adipose tissue insulin resistance. Furthermore, adipo-IR is associated with non-LDL-C lipid parameters instead of glycemic control in those receiving alogliptin.