Abstract
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.
| Original language | English |
|---|---|
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 13 |
| Issue number | 7 |
| Pages (from-to) | 639-43 |
| Number of pages | 5 |
| ISSN | 1462-8902 |
| DOIs | |
| Publication status | Published - Jul 2011 |
Keywords
- Blood Glucose
- C-Peptide
- Diabetes Mellitus, Type 2
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Glucagon-Like Peptide 1
- Humans
- Hypoglycemic Agents
- Infusions, Subcutaneous
- Male
- Middle Aged
- Peptide Fragments
- Placebos
- Postprandial Period
