TY - JOUR
T1 - Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus
AU - Torekov, Signe Sørensen
AU - Holst, J J
AU - Ehlers, M R
N1 - © 2013 John Wiley & Sons Ltd.
PY - 2014/5
Y1 - 2014/5
N2 - Aims: Any differences observed between natural glucagon-like peptide-1 (GLP-1) and studies obtained with analogues might call for renewed considerations concerning the use and design of such analogues. Thus, we aimed to evaluate the dose-response relationship of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes. Methods: We compared the efficacy and safety of three doses of recombinant GLP-1, ranging from 1.25 to 5.0pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control. Results: The mean decreases in HbA1c at endpoint (week 12) were significantly greater for all three rGLP-1 dose groups when each was compared with the placebo group, with the greatest decrease occurring in the 5.0pkm dose group (-1.3%, s.d.±0.18, p<0.001). The mean decreases in fasting plasma glucose from baseline to endpoint were significantly greater for all three rGLP-1 dose groups than for the placebo group, with the greatest decrease occurring in the 5.0pkm dose group (-26.0mg/dl, s.d.±8.5, p=0.02). Body weight was significantly reduced by 1.8kg (s.d.±1.3) in the 1.25pkm dose group only (p=0.04). Conclusions: Administration of rGLP-1 by CSCI over a 12-week period in combination with metformin and an SU had a dose dependent effect in lowering HbA1c and fasting plasma glucose. However, administration of rGLP-1 by CSCI may be less effective with respect to lowering of body weight compared with the daily and once weekly analogues.
AB - Aims: Any differences observed between natural glucagon-like peptide-1 (GLP-1) and studies obtained with analogues might call for renewed considerations concerning the use and design of such analogues. Thus, we aimed to evaluate the dose-response relationship of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes. Methods: We compared the efficacy and safety of three doses of recombinant GLP-1, ranging from 1.25 to 5.0pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control. Results: The mean decreases in HbA1c at endpoint (week 12) were significantly greater for all three rGLP-1 dose groups when each was compared with the placebo group, with the greatest decrease occurring in the 5.0pkm dose group (-1.3%, s.d.±0.18, p<0.001). The mean decreases in fasting plasma glucose from baseline to endpoint were significantly greater for all three rGLP-1 dose groups than for the placebo group, with the greatest decrease occurring in the 5.0pkm dose group (-26.0mg/dl, s.d.±8.5, p=0.02). Body weight was significantly reduced by 1.8kg (s.d.±1.3) in the 1.25pkm dose group only (p=0.04). Conclusions: Administration of rGLP-1 by CSCI over a 12-week period in combination with metformin and an SU had a dose dependent effect in lowering HbA1c and fasting plasma glucose. However, administration of rGLP-1 by CSCI may be less effective with respect to lowering of body weight compared with the daily and once weekly analogues.
U2 - 10.1111/dom.12240
DO - 10.1111/dom.12240
M3 - Journal article
C2 - 24251641
SN - 1462-8902
VL - 16
SP - 451
EP - 456
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 5
ER -
