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Clinical Trial
. 2023 Apr 13:16:1043-1054.
doi: 10.2147/DMSO.S403125. eCollection 2023.

Teneligliptin, a DPP-4 Inhibitor, Improves Vascular Endothelial Function via Divergent Actions Including Changes in Circulating Endothelial Progenitor Cells

Naoyuki Akashi  1 , Tomio Umemoto  1 , Hodaka Yamada  2 , Takayuki Fujiwara  3 , Kei Yamamoto  1 , Yousuke Taniguchi  1 , Kenichi Sakakura  1 , Hiroshi Wada  1 , Shin-Ichi Momomura  1 , Hideo Fujita  1
Affiliations
Clinical Trial

Teneligliptin, a DPP-4 Inhibitor, Improves Vascular Endothelial Function via Divergent Actions Including Changes in Circulating Endothelial Progenitor Cells

Naoyuki Akashi et al. Diabetes Metab Syndr Obes. .

Abstract

Purpose: Dipeptidyl peptidase-4 (DPP-4) inhibitors increase endothelial progenitor cells (EPCs) in peripheral blood circulation. However, the underlying mechanisms and effects on vascular endothelial function remain unclear. We evaluated whether the DPP-4 inhibitor teneligliptin increases circulating EPCs by inhibiting stromal-derived factor-1α (SDF-1α) and improves flow-mediated vascular dilatation (FMD) in type 2 diabetes mellitus patients with acute coronary syndrome (ACS) or its risk factors.

Patients and methods: This single-center, open-label, prospective, randomized controlled trial evaluated 17 patients (hemoglobin A1c ≤7.5% and peak creatinine phosphokinase <2000 IU/mL) with ACS or a history of ACS or multiple cardiovascular risk factors. Metabolic variables of glucose and lipids, circulating EPCs, plasma DPP-4 activity, and SDF-1α levels, and FMD were evaluated at baseline and 28 ± 4 weeks after enrollment. Patients were randomly assigned to either the teneligliptin (n = 8) or control (n = 9) groups.

Results: The DPP-4 activity (∆-509.5 ± 105.7 vs ∆32.8 ± 53.4 μU/mL) and SDF-1α levels (∆-695.6 ± 443.2 vs ∆11.1 ± 193.7 pg/mL) were significantly decreased after 28 weeks in the teneligliptin group than those in the control group. The number of EPCs showed an increasing trend in the teneligliptin treated group; albeit this did not reach statistical significance. Glucose and lipid levels were not significantly different between the groups before and after 28 weeks. However, FMD was significantly improved in the teneligliptin group when compared to the control group (∆3.8% ± 2.1% vs ∆-0.3% ± 2.9%, P=0.006).

Conclusion: Teneligliptin improved FMD through a mechanism other than increasing the number of circulating EPCs.

Keywords: DPP-4 inhibitor; endothelial progenitor cell; flow-mediated dilation; teneligliptin; type 2 diabetes mellitus.

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Conflict of interest statement

Dr Naoyuki Akashi reports grants from Mitsubishi Tanabe Pharma Corporation, during the conduct of the study. The authors report no other potential conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study flow chart.
Figure 2
Figure 2
Mean endothelial progenitor cells (EPCs) between baseline and 28 weeks in the teneligliptin and control groups. Temporal changes in EPC levels from baseline to 28 weeks were not significantly different between the groups (P = 0.13). The bar graph and error bars show the mean and standard deviation, respectively.
Figure 3
Figure 3
Mean flow-mediated dilatation (FMD) between baseline and 28 weeks in the teneligliptin and control groups. Temporal changes in FMD from baseline to 28 weeks were significantly increased in the teneligliptin group (3.8% ± 2.1%) compared with those in the control group (−0.3% ± 2.9%). The bar graph and error bars show the mean and standard deviation, respectively. *P <0.05, compared to the control group.
See this image and copyright information in PMC

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