title: Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles.
  
  
  METHODS
  In a double-blind, parallel, placebo-controlled trial, 47 patients were randomized to placebo or rGLP-1 (1.25, 2.5, 5.0 or 8.5 pmol/kg/min) by CSCI for 7 days. On day 1 (pretreatment) and on day 8, patients underwent monitoring of fasting, postprandial, and 11-h profiles of glucose and hormones.
  
  
  RESULTS
  Fasting serum glucose decreased by 76.2, 53.9, 37.0 and 22.7 mg/dl for the 8.5, 5.0, 2.5 and 1.25 pmol/kg/min rGLP-1 groups, respectively, compared to a decrease of 1.1 mg/dl for placebo (p = 0.0002, 0.005, 0.064 and 0.27, respectively). Mean 11-h serum glucose area under the curve decreased by 36.3, 23.3, 16.9 and 10.0% for 8.5, 5.0, 2.5 and 1.25 pmol/kg/min rGLP-1, respectively, compared to no change for placebo (p = 0.0001, 0.0019, 0.012 and 0.14, respectively). Mean fasting C-peptide increased dose dependently with rGLP-1 (p = 0.0023 for the highest dose) and decreased with placebo. There were no serious safety concerns and no instances of hypoglycaemia.
  
  
  CONCLUSIONS
  rGLP-1 produced continuous improvements in glycaemic control across a broad dose range of up to 8.5 pmol/kg/min.
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. Torekov@sund.ku.dk
authors.forename: S S
authors.initials: SS
authors.lastname: Torekov
authors.forename: M S
authors.initials: MS
authors.lastname: Kipnes
authors.forename: R E
authors.initials: RE
authors.lastname: Harley
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: M R
authors.initials: MR
authors.lastname: Ehlers
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D055104:Infusions, Subcutaneous; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000627:therapeutic use*; D010919:Placebos; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D010446:Peptide Fragments; D010919:Placebos; D052216:Glucagon-Like Peptide 1