Diabetology International

, Volume 7, Issue 2, pp 133–140 | Cite as

Complementary glucagonostatic and insulinotropic effects of DPP-4 inhibitors in the glucose-lowering action in Japanese patients with type 2 diabetes

  • Ken-ichi Hashimoto
  • Yukio HorikawaEmail author
  • Jun Takeda
Original Article


The dipeptidyl peptidase-4 (DPP-4) inhibitors have a low risk of causing hypoglycemia as monotherapy. However, insulin administration is frequently required, particularly in patients with type 2 diabetes and with reduced insulin secretory capacity. The effects of adding DPP-4 inhibitors were evaluated using continuous glucose monitoring (CGM) in Japanese patients with type 2 diabetes who were insufficiently controlled by basal insulin with biguanide. The effects of adding DPP-4 inhibitors on blood glucose and plasma insulin and glucagon levels were evaluated. Δ glucagon showed a significant association with post-prandial glucose increase in the group with diminished insulin secretory capacity, C-peptide index (CPI) <0.8 (p = 0.016), while Δ C-peptide reached significant association in the group with relatively intact insulin secretory capacity, CPI ≥0.8 (p = 0.017). The mean plasma glucose levels and M values were similarly improved in patients treated with the three DPP-4 inhibitors. Hypoglycemia did not occur in any of the DPP-4 inhibitor groups. In conclusion, complementary glucagonostatic and insulinotropic effects of adding DPP-4 inhibitors are involved in the glucose-lowering action of Japanese patients with type 2 diabetes according to their insulin secretory capacity. Such combination therapy may well be a superior therapeutic option for the treatment of diabetes in Japanese patients who often exhibit reduced insulin secretory capacity.


Type 2 diabetes mellitus DPP-4 inhibitors Hypoglycemia Glucagon Insulin 



Dipeptidyl peptidase-4


Continuous glucose monitoring


Basal supported oral therapy


Secretory units of islets in transplantation


C-peptide index


Glucagon like peptide-1


Glucose-dependent insulinotropic polypeptide


Fasting plasma glucose


Postprandial plasma glucose


C-peptide immunoreactivity


Immunoreactive glucagon


Analysis of variance


Neutral protamine hagedorn



We thank the patients for their kind contribution to this study. This work was supported by a Grant-in-Aid for Scientific Research from the Japanese Ministry of Science, Education, Sports, Culture, and Technology (No.25293228, 26293246).

Compliance with ethical standards

Conflict of interest

YH received honoraria for lectures from Astellas Pharma Inc. and scholarship grants from MSD. JT received honoraria for lectures from Astellas Pharma Inc., Sanofi K.K, Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Eli Lilly Japan K.K., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., MSD., Dainippon Sumitomo Pharma Co.,Ltd., Mitsubishi Tanabe Pharma Corporation, Boehringer Ingelheim, Taisho Toyama Pharmaceutical Co.Ltd. and Kowa Company, Ltd., and scholarship grants from Boehringer Ingelheim, Sanofi K.K, Ono Pharmaceutical Co. Ltd., Novo Nordisk Pharma Ltd., Novartis Pharma K.K., Sanwa Kagaku Kenkyusho Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly Japan K.K. Taisho Toyama Pharmaceutical Co.Ltd., MSD., Kowa Company, Ltd. and Kyowa Hakko Kirin Co.Ltd. K.H declares that he has no conflict of interest.

Human rights statement and informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later revision. Informed consent or substitute for it was obtained from all patients for being included in the study.


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Copyright information

© The Japan Diabetes Society 2015

Authors and Affiliations

  • Ken-ichi Hashimoto
    • 1
  • Yukio Horikawa
    • 1
    Email author
  • Jun Takeda
    • 1
  1. 1.Department of Diabetes and EndocrinologyGifu University Graduate School of MedicineGifuJapan

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