Teneligliptin, a Chemotype Prolyl-Thiazolidine-Based Novel Dipeptidyl Peptidase-4 Inhibitor with Insulin Sensitizing Properties.

Background And Objectives: Teneligliptin, a chemotype prolyl-thiazolidine-based novel dipeptidyl peptidase (DPP)-4 inhibitor, was preliminarily shown to reduce insulin resistance in patients with type 2 diabetes mellitus (T2DM). The objective of this study is to further investigate the insulin sensitising properties of teneligliptin in comparison to those of sitagliptin.

Methods: Treatment-naïve subjects with T2DM were administered 20 mg/day teneligliptin monotherapy (n = 45). As a comparator, 25-50 mg/day sitagliptin monotherapy was performed in a non-randomized manner (n = 71). No other drugs were administered. At 3 months, levels of diabetic parameters were compared with those at baseline.

Results: At 3 months, while similar reductions of glycated hemoglobin (HbA1c) levels were observed with these two drugs, indexes for insulin sensitivity [homeostasis model assessment (HOMA)-R and 20/(C-peptide × fasting blood glucose (FBG)) levels] ameliorated only with teneligliptin. Then, the subjects were divided into two groups representing distinct degrees of insulin resistance; high HOMA-R (≥4) and low HOMA-R (<2) groups. With teneligliptin, similar decreases of HbA1c levels were observed in high (9.85-7.66 %, p < 0.0005) and low (10.12-8.51 %, p < 0.01) HOMA-R groups. HOMA-R (-32.6 %, p < 0.05) and non-high density lipoprotein cholesterol (non-HDL-C, -6 %, p < 0.05) levels significantly decreased and 20/(C-peptide × FBG) levels significantly increased (53 %, p < 0.001) in high HOMA-R group. HOMA-B levels increased in both groups with significant inter-group differences (+101.7 % in low HOMA-R group vs. +55.4 % in high HOMA-R group). Group 2. With sitagliptin, similar decreases of HbA1c levels were observed from those of teneligliptin in either high or low HOMA-R group, but no changes of HOMA-R, non-HDL-C or 20/(C-peptide × FBG) levels were noted. Increases of HOMA-B levels with sitagliptin were comparable to those with teneligliptin in either high or low HOMA-R group.

Conclusions: These results indicate that: (i) teneligliptin ameliorates insulin sensitivity and non-HDL-C levels in subjects with high degrees of insulin resistance. This is not the case with sitagliptin, though similar glycemic efficacies were observed. (ii) glycemic efficacy of teneligliptin may be determined by the balance of its capacity in modulating insulin resistance and beta-cell function depending on the degrees of baseline insulin resistance.