TY - JOUR
T1 - Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes
AU - Torekov, Signe Sørensen
AU - Kipnes, M S
AU - Harley, R E
AU - Holst, J J
AU - Ehlers, M R
N1 - © 2011 Blackwell Publishing Ltd.
PY - 2011/7
Y1 - 2011/7
N2 - Aim: 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.
AB - Aim: 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.
KW - Blood Glucose
KW - C-Peptide
KW - Diabetes Mellitus, Type 2
KW - Dose-Response Relationship, Drug
KW - Double-Blind Method
KW - Female
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Hypoglycemic Agents
KW - Infusions, Subcutaneous
KW - Male
KW - Middle Aged
KW - Peptide Fragments
KW - Placebos
KW - Postprandial Period
U2 - 10.1111/j.1463-1326.2011.01388.x
DO - 10.1111/j.1463-1326.2011.01388.x
M3 - Journal article
C2 - 21362122
SN - 1462-8902
VL - 13
SP - 639
EP - 643
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 7
ER -
