title: No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects.
abstract: OBJECTIVE
  It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels.
  
  
  METHODS
  A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min.
  
  
  RESULTS
  Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT.
  
  
  CONCLUSIONS
  The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.
authors.affiliation: Institute of Pharmacology, University of Aarhus, University Park 1240, Aarhus C, Denmark. lerche@ki.au.dk
authors.forename: Susanne
authors.initials: S
authors.lastname: Lerche
authors.forename: Liselotte
authors.initials: L
authors.lastname: Soendergaard
authors.forename: Joergen
authors.initials: J
authors.lastname: Rungby
authors.forename: Niels
authors.initials: N
authors.lastname: Moeller
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Ole E
authors.initials: OE
authors.lastname: Schmitz
authors.forename: Birgitte
authors.initials: B
authors.lastname: Brock
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D005215:Fasting / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000097:blood; D005951:Glucose Tolerance Test; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology*; D055104:Infusions, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000008:administration & dosage
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D019382:Human Growth Hormone; D052216:Glucagon-Like Peptide 1; D009638:Norepinephrine