title: Counter-regulatory hormone responses to hypoglycaemia in people with type 1 diabetes after 4 weeks of treatment with liraglutide adjunct to insulin: a randomized, placebo-controlled, double-blind, crossover trial.
abstract: OBJECTIVE
  To investigate the effect of glucagon-like peptide 1 receptor agonist liraglutide on the counter-regulatory hormone response to hypoglycaemia in type 1 diabetes.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled, single-centre trial, in which a total of 45 adults with type 1 diabetes [mean ± standard deviation age 34.5 ± 11.2 years, BMI 23.9 ± 2.4 kg/m(2) , glycated haemoglobin (HbA1c) 7.6 ± 0.8%, diabetes duration 16.6 ± 9.4 years] underwent a hypoglycaemic clamp after 4 weeks' crossover treatment with once-daily liraglutide/placebo added to insulin in one of three liraglutide dose groups: 0.6 mg (n = 15); 1.2 mg (n = 14); and 1.8 mg (n = 16). The main outcome measure was glucagon concentration at nadir plasma glucose (2.5 mmol/l). Clinical outcomes were also evaluated. Five participants were withdrawn from the trial; three because of adverse events. All participants were included in the analysis.
  
  
  RESULTS
  Glucagon concentration at nadir plasma glucose was modest, trending towards lower concentrations at increasing liraglutide dose versus placebo: 34.7 versus 38.1 pg/ml, p = 0.555 (0.6 mg); 28.8 versus 37.2 pg/ml, p = 0.126 (1.2 mg); and 28.4 versus 37.5 pg/ml, p = 0.092 (1.8 mg). There was no difference, however, between liraglutide and placebo in incremental change in glucagon during hypoglycaemia. Other counter-regulatory hormone levels increased during hypoglycaemia with no systematic differences between groups. Glucose infusion rates were significantly lower with liraglutide versus placebo during the clamp. After 4 weeks' treatment, HbA1c remained unchanged in the liraglutide and placebo groups. Greater reductions in insulin dose and body weight were seen with liraglutide versus placebo.
  
  
  CONCLUSIONS
  Liraglutide did not compromise hypoglycaemic responses in type 1 diabetes after 4 weeks' treatment.
authors: Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: T R
authors: TR
authors: Pieber
authors: Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Deller
authors: Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors: S
authors: S
authors: Korsatko
authors: Novo Nordisk A/S, Søborg, Denmark.
authors: L
authors: L
authors: Jensen
authors: Novo Nordisk A/S, Søborg, Denmark.
authors: E
authors: E
authors: Christiansen
authors: Novo Nordisk A/S, Søborg, Denmark.
authors: J
authors: J
authors: Madsen
authors: Academic Unit of Diabetes, Endocrinology and Metabolism, University of Sheffield, Sheffield, UK.
authors: S R
authors: SR
authors: Heller
mesh_terms: D000328:Adult; D001835:Body Weight; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069450:Liraglutide; C517652:hemoglobin A1c protein, human
keywords: GLP-1; catecholamines; counter-regulation; glucagon; glucose infusion rate; hypoglycaemia; hypoglycaemic clamp; incretin therapy; liraglutide; type 1 diabetes