Glucagon-Like Peptide-1 Infusion Must Be Maintained for 24 h/day to Obtain Acceptable Glycemia in Type 2 Diabetic Patients Who Are Poorly Controlled on Sulphonylurea Treatment

Abstract

OBJECTIVE—To assess the efficacy and safety of glucagon-like peptide-1 (GLP-1) on the plasma glucose level when given as a continuous infusion for either 16 or 24 h per day to type 2 diabetic patients who were poorly controlled on sulfonylurea treatment. RESEARCH DESIGN AND METHODS—This single-center, randomized, parallel, double-blind, placebo-controlled trial was conducted in 40 hospitalized patients who were randomized to receive infusions of either placebo or GLP-1 4 or 8 ng · kg–1 · min–1 for either 16 or 24 h per day for 7 days. At predetermined intervals, 24-h profiles of glucose, glucagon, and insulin were measured. Adverse events and clinical chemistry and hematology were recorded. RESULTS—For all active treatment groups, the change in average glucose (area under the curve [AUC] for day 7 minus AUC for day 0 divided by 24 h) was statistically significantly different from placebo (P ≤ 0.001). The GLP-1 8 ng · kg–1 · min–1 dose given for 24 h was more efficacious than any of the other doses (P ≤ 0.05). Nocturnal and fasting plasma glucose levels at day 7 were greater in the 16-h groups compared with the 24-h groups (P ≤ 0.05). Insulin AUC did not show any treatment effect for any of the treatment groups when change was assessed from day 0 to day 7. However, for the 16-h groups, the pattern of the insulin profiles changed; the insulin profiles were considerably higher during the initial 3–4 h after restart of the GLP-1 infusion on day 7, although there was a tendency for insulin levels to decrease during the afternoon and evening. Glucagon AUC decreased significantly for all active treatment groups compared with placebo. GLP-1 was generally well tolerated. CONCLUSIONS—This study demonstrated that GLP-1 should be given continuously to obtain the most optimal glycemic control. Because of the short plasma half-life of native GLP-1, long-acting derivatives should be developed to make GLP-1 treatment clinically relevant.