title: 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.
abstract: 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 2.5 mmol/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.
authors: Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan.|Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.|Center for Metabolism and Clinical Nutrition, Kansai Electric Power Hospital, Osaka, Japan.|Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Daisuke
authors: D
authors: Yabe
authors: Hakata Clinic, SOUSEIKAI, Fukuoka, Japan.
authors: Takashi
authors: T
authors: Eto
authors: Hakata Clinic, SOUSEIKAI, Fukuoka, Japan.
authors: Masanari
authors: M
authors: Shiramoto
authors: Hakata Clinic, SOUSEIKAI, Fukuoka, Japan.
authors: Shin
authors: S
authors: Irie
authors: Division of Biostatistics, Clinical Research Center, Aichi Medical University Hospital, Nagakute, Japan.
authors: Kenta
authors: K
authors: Murotani
authors: Departments of Endocrinology and Diabetes Metabolic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yusuke
authors: Y
authors: Seino
authors: Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan.|Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.
authors: Hitoshi
authors: H
authors: Kuwata
authors: Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan.|Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.
authors: Takeshi
authors: T
authors: Kurose
authors: Division of Molecular and Metabolic Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors: Susumu
authors: S
authors: Seino
authors: Department of Clinical Sciences, Lund University, Lund, Sweden.
authors: Bo
authors: B
authors: Ahrén
authors: Yutaka Seino Distinguished Center for Diabetes Research, Kansai Electric Power Medical Research Institute, Kobe, Japan.|Center for Diabetes, Endocrinology and Metabolism, Kansai Electric Power Hospital, Osaka, Japan.
authors: Yutaka
authors: Y
authors: Seino
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004837:Epinephrine / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D015309:Glucose Clamp Technique; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007003:Hypoglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007564:Japan; D000069476:Linagliptin / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D019382:Human Growth Hormone; D000069476:Linagliptin; D000069450:Liraglutide; D005934:Glucagon; D006854:Hydrocortisone; D009638:Norepinephrine; D004837:Epinephrine; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: 
  DPP-4 inhibitor; 
  GLP-1 receptor agonist; glucagon response; hypoglycaemia; sympatho-adrenal response