Subcutaneous Administration of Glucagon-Like Peptide 1
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/m remained on usual glucose-lowering therapy and eight patients (aged 73 ± 1 years, BMI 27 ± 1 kg/m, after discontinuing hypoglycemic medications, received GLP-1 delivered by continuous subcutaneous infusion for 12 weeks. The maximum dose was 120 pmol · kg · h. 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 · min; 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.

Glucagon-like peptide 1 (GLP-1), which is secreted from enteroendocrine cells of the intestine in response to food, is insulinotropic in type 2 diabetic patients. Even with pharmacological concentrations, it does not cause hypoglycemia because it has little or no insulinotropic effect on glucose levels <4 mmol/l. GLP-1 is, therefore, a promising agent for the treatment of type 2 diabetes.

Aging is characterized by a progressive increase in the prevalence of diabetes; by 75 years of age, ~20% of the population is afflicted. Many patients are treated with sulfonylureas and ultimately with insulin. Unfortunately, the risk of severe hypoglycemia associated with these agents increases with age. We previously demonstrated that GLP-1 has insulinotropic activity in elderly diabetic patients and it enhances their insulin- and non-insulin-mediated glucose uptake. Because of its ability to ameliorate multiple metabolic defects and because hypoglycemia might not be an issue, GLP-1 and its analogs may prove to be valuable therapeutic agents in this population. GLP-1 also has pleiotropic effects: it decreases glucagon release, inhibits gastric emptying, and increases islet cell proliferation and differentiation. Therefore, it might have long-term beneficial consequences in type 2 diabetes not seen with other therapies. We conducted a 3-month trial of continuous subcutaneous administration of GLP-1 in elderly type 2 diabetic patients. We wished to see whether GLP-1 would maintain its insulinotropic properties when given continuously over such a long period, and we wished to compare its efficacy to the best standard of care available, using oral agents. Because elderly individuals have the highest prevalence of diabetes, we believed it was appropriate to study that particular age-group.