Effects of DPP-4 inhibitor linagliptin and GLP-1 receptor agonist liraglutide on physiological response to hypoglycaemia in Japanese subjects with type 2 diabetes: A randomized, open-label, 2-arm parallel comparative, exploratory trial

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Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce the risk of hypoglycaemia, possibly through augmentation of glucose-dependent insulinotropic polypeptide (GIP) action, but not that of glucagon-like peptide-1 (GLP-1) on glucagon secretion. To examine this model in Japanese individuals with type 2 diabetes (T2D), the effects of the DPP-4 inhibitor linagliptin on glucagon and other counter-regulatory hormone responses to hypoglycaemia were evaluated and compared with those of the GLP-1 receptor agonist liraglutide in a multi-centre, randomized, open-label, 2-arm parallel comparative, exploratory trial. Three-step hypoglycaemic clamp glucose tests preceded by meal tolerance tests were performed before and after 2-week treatment with the drugs. Glucagon levels were increased during the hypoglycaemic clamp test at 2.5mmol/L. This increase was similar in the linagliptin and liraglutide groups, both before and after the 2-week treatment. Changes in other counter-regulatory hormones (ie, growth hormone, cortisol, epinephrine and norepinephrine) were also similar between the groups, but were suppressed substantially after 2-week treatment compared to baseline. In conclusion, we confirmed that the glucagon response to hypoglycaemia was not affected by linagliptin or liraglutide treatment in Japanese individuals with T2D.


  • Daisuke Yabe
  • Takashi Eto
  • Masanari Shiramoto
  • Shin Irie
  • Kenta Murotani
  • Yusuke Seino
  • Hitoshi Kuwata
  • Takeshi Kurose
  • Susumu Seino
  • Bo Ahrén
  • Yutaka Seino
External organisations
  • Kobe university
  • Hakata Clinic
  • Aichi Medical University
  • Nagoya University
  • Kansai Electric Power Medical Research Institute (KEPMRI)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • GLP-1 receptor agonist, DPP-4 inhibitor, Glucagon response, Hypoglycaemia, Sympatho-adrenal response
Original languageEnglish
Pages (from-to)442-447
JournalDiabetes, Obesity and Metabolism
Issue number3
Publication statusPublished - 2017
Publication categoryResearch