532 Original Article
Authors
M. Kusunoki1, D. Sato2, T. Nakamura2, Y. Oshida3, H. Tsutsui4, Y. Natsume5, K. Tsutsumi6, T. Miyata7
Affiliations
Affiliation addresses are listed at the end of the article
Key words ▶ teneligliptin ● ▶ dipeptidyl peptidase-4 ● inhibitor ▶ insulin resistance ● ▶ HDL-cholesterol ● ▶ triglyceride ●
Abstract
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Dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to improve the glycemic control and blood hemoglobin A1c (HbA1c) concentrations. However, there are few reports as yet suggesting that DPP-4 inhibitors may also improve insulin resistance and the serum lipid profile in the clinical setting. This study was aimed at investigating the effect of 14-week treatment with teneligliptin (20 mg/day) on the homeostasis model assessment ratio (HOMA-R), an indicator of insulin resistance, and serum lipid profile
Introduction
▼ received 30.07.2014 accepted 05.09.2014 Bibliography DOI http://dx.doi.org/ 10.1055/s-0034-1390419 Published online: November 4, 2014 Drug Res 2015; 65: 532–534 © Georg Thieme Verlag KG Stuttgart · New York ISSN 2194-9379 Correspondence M. Kusunoki Department of Internal Medicine Medical Clinic Aichi Medical University, 2-12-1 Higashisakura Higashi-ku Nagoya 461-0005 Japan Tel.: + 81/52/931 2261 Fax: + 81/52/931 4841
[email protected] Incretin is a hormone released from the alimentary tract in response to food ingestion and stimulates insulin secretion from the β cells of the pancreas [1, 2]. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that inactivates incretin; therefore, inhibition of DPP-4 results in inhibition of incretin degradation, and a sustained insulinotropic action [3, 4]. Based on this pharmacological action, DPP-4 inhibitors were developed as antidiabetic agents. Numerous clinical studies have reported the usefulness of DPP-4 inhibitors in controlling the blood glucose levels in type 2 diabetic patients. Also, a number of rodent studies demonstrating the effects of linagliptin, teneligliptin and anagliptin in improving insulin resistance have been reported [5–7], and it has also been pointed out that sitagliptin may suppress inflammation of adipose tissue [8]. On the other hand, reports on the effects of DPP-4 inhibitors in improving insulin resistance and the serum lipid profile in humans are still few. Since it is widely recognized that insulin resistance and hyperlipidemia contribute to the risk of arteriosclerosis [9, 10], we considered it to be of vital importance to clarify
Kusunoki M et al. Teneligliptin Alters Insulin Resistance … Drug Res 2015; 65: 532–534
in 9 patients with type 2 diabetes. The treatment produced a significant decrease of the blood glucose and HbA1c concentration (blood glucose: p = 0.008; HbA1c: p = 0.038), and also improved HOMA-R (p = 0.039). Furthermore, the patients showed elevation of the serum HDL-cholesterol level (p = 0.032), and a tendency towards reduction of the serum triglyceride level. The results indicate that teneligliptin acts not only to improve the blood glucose control, but also to improve the insulin resistance and serum lipid profile in Japanese type 2 diabetes patients.
the effects of DPP-4 inhibitors on insulin resistance and hyperlipidemia. In the present study, we prospectively investigated the effects of teneligliptin, a DPP-4 inhibitor, on the insulin resistance and serum lipid profile in Japanese type 2 diabetes patients.
Materials and Methods
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Study design
9 patients with type 2 diabetes (4 males and 5 females; age: 63 ± 9 years old; body weight: 60 ± 9 kg; body mass index: 23.3 ± 2.5 kg/m2) were enrolled in this study. The diabetics above the age of 80 and/or the patients having severe nephropathy were dropped out. The subjects were provided an explanation about the method and objective of the study, and gave informed consent for participation in the study to the attending physician. This trial was registered at an official registry as a non-blinded prospective study (ID: UMIN000014982). Teneligliptin 20 mg (TENELIA®, Mitsubishi Tanabe Pharma, Osaka, Japan) was administered orally once a day, before breakfast, for 14 weeks. We dealt monotherapy in this study, and other
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DPP-4 Inhibitor Teneligliptin Improves Insulin Resistance and Serum Lipid Profile in Japanese Patients with Type 2 Diabetes
Original Article 533
Blood analyses
The Health Care Center, Medical Association of Handa City (Handa, Japan) was entrusted to determine the blood data. Blood glucose level (BG) and serum levels of total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C) and triglyceride (TG) were evaluated with an automated analyzer (BioMajesty™ JCA-BM 8000; JEOL, Tokyo, Japan). Serum insulin level was measured by the enzyme-linked immunosorbent assay. Measurement of the serum adiponectin level was carried out using the Human Adiponectin Latex Kit (Otsuka Pharmaceutical, Tokyo, Japan). HbA1c levels were measured by high-performance liquid chromatography with an Automated Glycohemoglobin Analyzer (Tosoh, Tokyo, Japan).
Before
14-week
P value
administration Blood glucose (mg/dl) HbA1c ( %) HOMA-R Adiponectin (μg/ml)
130 ± 28 6.6 ± 1.2 2.5 ± 1.7 11.6 ± 9.2
105 ± 14 5.9 ± 0.4 1.6 ± 1.0 9.9 ± 6.6
0.008 0.038 0.039 0.155
Data are expressed as mean ± SD (n = 9). Significantly different from the values in the respective before values
Table 2 Effects of 14-week 20 mg/day administration of teneligliptin on serum lipids in Japanese patients with type 2 diabetes. Before
14-week
P value
administration Total cholesterol (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) Triglyceride (mg/dl)
196 ± 43 55 ± 15 122 ± 43 189 ± 140
174 ± 29 62 ± 16 103 ± 29 114 ± 44
0.105 0.032 0.164 0.080
Data are expressed as mean ± SD (n = 9). Significantly different from the values in the respective before values
Statistical analysis
Data were expressed as mean ± SD. For comparison of pre- vs. post-treatment data, a paired t-test was employed in SPSS ver. 15. The statistical significance of differences in the serum triglyceride levels was performed after log-transformation of the serum triglyceride concentrations. Statistical significance was set at p