Prediction of the effect on antihyperglycaemic action of sitagliptin by plasma active form glucagon-like peptide-1.
OBJECTIVE
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.


CONCLUSIONS
Plasma fasting active GLP-1 is an independent predictive marker for the efficacy of dipeptidyl peptidase 4 inhibitor sitagliptin.
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.
Akifumi
A
Kushiyama
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.
Takako
T
Kikuchi
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
K
Tanaka
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.
Tazu
T
Tahara
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.
Toshiko
T
Takao
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.
Yukiko
Y
Onishi
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.
Yoko
Y
Yoshida
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.
Shoji
S
Kawazu
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.
Yasuhiko
Y
Iwamoto
Active form glucagon-like peptide-1; Dipeptidyl peptidase-4 inhibitor; Hemoglobin A1c; Regression analysis