Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes.
OBJECTIVE
Glucagon-like peptide 1 (GLP-1) is an insulinotropic gut hormone that, when given exogenously, may be a useful agent in the treatment of type 2 diabetes. We conducted a 3-month trial to determine the efficacy and safety of GLP-1 in elderly diabetic patients.


METHODS
A total of 16 patients with type 2 diabetes who were being treated with oral hypoglycemic agents were enrolled. Eight patients (aged 75 +/- 2 years, BMI 27 +/- 1 kg/m(2)) remained on usual glucose-lowering therapy and eight patients (aged 73 +/- 1 years, BMI 27 +/- 1 kg/m(2)), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol x kg(-1). h(-1). Patients recorded their capillary blood glucose (CBG) levels (four times per day, 3 days per week) and whenever they perceived hypoglycemic symptoms. The primary end points were HbA(1c) and CBG determinations. Additionally, changes in beta-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined.


RESULTS
HbA(1c) levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of <or=3.6 mmol/l during the study, and only 1 such measurement (3.5 mmol/l) was recorded in the GLP-1 group. Infusion of GLP-1 enhanced glucose-induced insulin secretion (pre: 119 +/- 21; post: 202 +/- 51 pmol/l; P < 0.05) and insulin-mediated glucose disposal (pre: 29.8 +/- 3.3; post: 35.9 +/- 2.3 micromol x kg(-1 x min(-1); P < 0.01). No effect of GLP-1 treatment was seen on the fasting plasma ghrelin levels. Although plasma ghrelin levels decreased during both portions of the clamp, a drug effect was not present.


CONCLUSIONS
A GLP-1 compound is a promising therapeutic option for elderly diabetic patients.
D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004343:Drug Implants; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000008:administration & dosage* / Q000009:adverse effects; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D011498:Protein Precursors / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D001786:Blood Glucose; D002096:C-Peptide; D004343:Drug Implants; D005230:Fatty Acids, Nonesterified; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors