Effects of 3 months of continuous subcutaneous administration of glucagon-like peptide 1 in elderly patients with type 2 diabetes

Diabetes Care. 2003 Oct;26(10):2835-41. doi: 10.2337/diacare.26.10.2835.

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/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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Implants
  • Fasting
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucagon / administration & dosage*
  • Glucagon / adverse effects
  • Glucagon-Like Peptide 1
  • Glycated Hemoglobin / metabolism
  • Humans
  • Injections, Subcutaneous
  • Insulin / blood
  • Male
  • Peptide Fragments / administration & dosage*
  • Peptide Fragments / adverse effects
  • Protein Precursors / administration & dosage*
  • Protein Precursors / adverse effects
  • Treatment Outcome

Substances

  • Blood Glucose
  • C-Peptide
  • Drug Implants
  • Fatty Acids, Nonesterified
  • Glycated Hemoglobin A
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon