Clinical Trials Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jun 10, 2016; 7(11): 230-238
Published online Jun 10, 2016. doi: 10.4239/wjd.v7.i11.230
Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1
Akifumi Kushiyama, Takako Kikuchi, Kentaro Tanaka, Tazu Tahara, Toshiko Takao, Yukiko Onishi, Yoko Yoshida, Shoji Kawazu, Yasuhiko Iwamoto
Akifumi Kushiyama, Takako Kikuchi, Kentaro Tanaka, Tazu Tahara, Toshiko Takao, Yukiko Onishi, Yoko Yoshida, Shoji Kawazu, Yasuhiko Iwamoto, Division of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, Tokyo 103-0002, Japan
Kentaro Tanaka, Department of Nephrology, School of Medicine, Faculty of Medicine, Toho University, Tokyo 103-0002, Japan
Author contributions: Kushiyama A designed research; Kikuchi T, Tahara T, Takao T, Onishi Y and Yoshida Y performed research; Kushiyama A and Tanaka K analyzed data; Kushiyama A, Kawazu S and Iwamoto Y wrote paper.
Institutional review board statement: The protocol was approved by the Institutional Review Board (IRB) of the Institute for Adult Diseases, Asahi Life Foundation.
Clinical trial registration statement: The study is a prospective, single-arm study and was registered at UMIN-CTR (Registration NO: UMIN000010645).
Informed consent statement: All of the subjects gave written informed consent to be included in this study.
Conflict-of-interest statement: Not declared.
Data sharing statement: The authors declare no conflicts of interest regarding this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Akifumi Kushiyama, MD, PhD, Division of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, 2-2-6 Nihonbashi, Bakurocho, Chuo-ku, Tokyo 103-0002, Japan. kusiyaa-tky@umin.ac.jp
Telephone: +81-3-3639-5501 Fax: +81-3-36395520
Received: January 22, 2016
Peer-review started: January 22, 2016
First decision: March 1, 2016
Revised: March 22, 2016
Accepted: April 21, 2016
Article in press: April 22, 2016
Published online: June 10, 2016
Processing time: 132 Days and 23.2 Hours
Abstract

AIM: To investigate whether active glucagon-like peptide-1 (GLP-1) is a prediction Factor of Effect of sitagliptin on patients with type 2 diabetes mellitus (GLP-1 FEST:UMIN000010645).

METHODS: Seventy-six patients with type 2 diabetes, who had insufficient glycemic control [Hemoglobin A1c (HbA1c) ≥ 7%] in spite of treatment with metformin and/or sulfonylurea, were included in the investigation. Patients were divided into three groups by tertiles of fasting plasma active GLP-1 level, before the administration of 50 mg sitagliptin.

RESULTS: At baseline, body mass index, serum UA, insulin and HOMA-IR were higher in the high active GLP-1 group than in the other two groups. The high active GLP-1 group did not show any decline of HbA1c (7.6% ± 1.4% to 7.5% ± 1.5%), whereas the middle and low groups indicated significant decline of HbA1c (7.4 ± 0.7 to 6.8 ± 0.6 and 7.4 ± 1.2 to 6.9 ± 1.3, respectively) during six months. Only the low and middle groups showed a significant increment of active GLP-1, C-peptide level, a decreased log and proinsulin/insulin ratio after administration. In logistic analysis, the low or middle group is a significant explanatory variable for an HbA1c decrease of ≥ 0.5%, and its odds ratio is 4.5 (1.40-17.6) (P = 0.01) against the high active GLP-1 group. This remains independent when adjusted for HbA1c level before administration, patients’ medical history, medications, insulin secretion and insulin resistance.

CONCLUSION: Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.

Keywords: Dipeptidyl peptidase-4 inhibitor; Active form glucagon-like peptide-1; Hemoglobin A1c; Regression analysis

Core tip: This clinical trials study revealed novel non-responders for the sitagliptin treatment of patients with type 2 diabetes. The fasting active form of glucagon-like peptide-1 (GLP-1) is related to Hemoglobin A1c (HbA1c) lowering and is independent of the previously reported factors associated with non-responders, such as high body mass index or low baseline HbA1c. These non-responders did not show fasting active GLP-1 elevation after sitagliptin administration, nor following ameliorated beta cell function and insulin secretion. The mechanism of poor responsiveness is still not unveiled, however, measuring active GLP-1 might be a good marker for prognosis, and may help clarifying one aspect of response variation against sitagliptin.