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

¹ Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
² National Institute on Aging, National Institutes of Health, Baltimore, Maryland
³ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
⁴ Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Dariush Elahi, PhD, Massachusetts General Hospital, Geriatric Research Laboratory, GRB SB 0015, 55 Fruit St., Boston, MA 02114. E-mail: delahi{at}partners.org

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 HbA_1c and CBG determinations. Additionally, changes in ß-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 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.

Abbreviations: CBG, capillary blood glucose • GLP-1, glucagon-like peptide 1 • NEFA, nonesterified fatty acid

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