title: Effects of sitagliptin on counter-regulatory and incretin hormones during acute hypoglycaemia in patients with type 1 diabetes: a randomized double-blind placebo-controlled crossover study.
abstract: OBJECTIVE
  To assess whether the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin affects glucagon and other counter-regulatory hormone responses to hypoglycaemia in patients with type 1 diabetes.
  
  
  METHODS
  We conducted a single-centre, randomized, double-blind, placebo-controlled, three-period crossover study. We studied 16 male patients with type 1 diabetes aged 18-52 years, with a diabetes duration of 5-20 years and intact hypoglycaemia awareness. Participants received sitagliptin (100 mg/day) or placebo for 6 weeks and attended the hospital for three acute hypoglycaemia studies (at baseline, after sitagliptin treatment and after placebo). The primary outcome was differences between the three hypoglycaemia study days with respect to plasma glucagon responses from the initialization phase of the hypoglycaemia intervention to 40 min after onset of the autonomic reaction.
  
  
  RESULTS
  Sitagliptin treatment significantly increased active levels of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. No significant differences were observed for glucagon or adrenergic counter-regulatory responses during the three hypoglycaemia studies. Growth hormone concentration at 40 min after occurrence of autonomic reaction was significantly lower after sitagliptin treatment [median (IQR) 23 (0.2-211.0) mEq/l] compared with placebo [median (IQR) 90 (8.8-180) mEq/l; p = 0.008].
  
  
  CONCLUSIONS
  Sitagliptin does not affect glucagon or adrenergic counter-regulatory responses in patients with type 1 diabetes, but attenuates the growth hormone response during late hypoglycaemia.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: Schopman
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: J B L
authors.initials: JBL
authors.lastname: Hoekstra
authors.affiliation: Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: B M
authors.initials: BM
authors.lastname: Frier
authors.affiliation: Department of Clinical Chemistry, Laboratory of Endocrinology and Radiochemistry, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: M T
authors.initials: MT
authors.lastname: Ackermans
authors.affiliation: Department of Internal Medicine, Tergooi, Hilversum, The Netherlands.
authors.forename: J J J
authors.initials: JJJ
authors.lastname: de Sonnaville
authors.affiliation: Department of Internal Medicine, University Medical Center, Utrecht, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Stades
authors.affiliation: Department of Internal Medicine, Westfriesgasthuis, Hoorn, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Zwertbroek
authors.affiliation: Department of Biomedical Sciences, NNF Centre for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Biomedical Sciences, NNF Centre for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Biomedical Sciences, NNF Centre for Basic Metabolic Research, Panum Institute, University of Copenhagen, Copenhagen, Denmark.|Department of Internal Medicine, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: F K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Holleman
mesh_terms: D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism; D005934:Glucagon / Q000187:drug effects*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D013006:Growth Hormone / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000209:etiology; D054795:Incretins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000068900:Sitagliptin Phosphate / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D013006:Growth Hormone; D005934:Glucagon; D000068900:Sitagliptin Phosphate
keywords: counter-regulation; dipeptidyl peptidase-4; glucagon; glucagon-like peptide-1; glucose-dependent insulinotropic polypeptide; hypoglycaemia; incretin hormones; type 1 diabetes mellitus