Effects of 3 Months of Continuous Subcutaneous Administration of Glucagon-Like Peptide 1 in Elderly Patients With Type 2 Diabetes

Abstract

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. RESEARCH DESIGN AND 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/m2) remained on usual glucose-lowering therapy and eight patients (aged 73 ± 1 years, BMI 27 ± 1 kg/m2), after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol · 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 HbA1c and CBG determinations. Additionally, changes in β-cell sensitivity to glucose, peripheral tissue sensitivity to insulin, and changes in plasma ghrelin levels were examined. RESULTS—HbA1c levels (7.1%) and body weight were equally maintained in both groups. The usual treatment group had a total of 87 CBG measurements of ≤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 μmol · kg−1 · 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.