Influence of glucagon-like peptide 1 on fasting glycemia in type 2 diabetic patients treated with insulin after sulfonylurea secondary failure

OBJECTIVE - Glucagon-like peptide 1 (GLP-1) has glucose-dependent insulinotropic and glucagonostatic actions in type 2 diabetic patients on diet and on oral agents. It is not known, however, whether after secondary sulfonylurea failure, GLP-1 is still effective. RESEARCH DESIGN AND METHODS - Therefore, 10 type 2 diabetic patients (6 women, 4 men; age 65 +/- 10 years, BMI 30.4 +/- 5.1 kg/m(2), HbA(1c), 8.2 +/- 1.5%, 6 +/- 3 [2-13] years after starting insulin treatment) were examined in the fasting slate after discontinuing NPH insulin on the evening before the two study days. GLP-1 (1.2 pmol.kg(-1).min(-1)) or placebo (NaCl with 1% human serum albumin) were infused over 6 h. Plasma glucose (glucose oxidase) insulin (IMx), and C-peptide (enzyme-linked immunosorbent assay) were measured. Statistical analysis was performed using repeated measures analysis of variance. RESULTS - Fasting plasma glucose was 9.4 + 0.5 mmol/l and was reduced by GLP-1 to 5.3 +/- 0.3 (3.9-7.3) mmol/l (placebo: 8.2 +/- 0.7 mmol/l; P < 0.0001). GLP-1 transiently increased insulin (from 115 +/- 31 to 222 +/- 64 pmol/l at 150 min; P < 0.0001) and C-peptide (from 1.00 +/- 0.12 to 1.90 +/- 0.23 nmol/l at 120 min; P < 0.0001) with no effect of placebo. Glucagon and free fatty acids were lowered transiently. After normalization of plasma glucose, insulin and C-peptide concentrations became lower again during the ongoing administration of exogenous GLP-1, and no hypoglycemia occurred. CONCLUSIONS - It is concluded that exogenous GLP-1 effectively lowers plasma glucose concentrations in advanced type 2 diabetes long after sulfonylurea secondary failure. These findings may broaden the applicability of GLP-1-derived drugs as a new treatment to nearly all type 2 diabetic patients.