Normalization of fasting glycaemia by intravenous GLP-1 ([7-36 amide] or [7-37]) in Type 2 diabetic patients

Intravenous GLP‐1 [7‐36 amide] can normalize fasting hyperglycaemia in Type 2 diabetic patients. Whether GLP‐1 [7‐37] has similar effects and how quickly plasma glucose concentrations revert to hyperglycaemia after stopping GLP‐1 is not known. Therefore, 8 patients with Type 2 diabetes (5 female, 3 male; 65 ± 6 years; BMI 34.3 ± 7.9 kg m−2; HbA1c 9.6 ± 1.2 %; treatment with diet alone (n = 2), sulphonylurea (n = 5), metformin (n = 1)) were examined twice in randomized order. GLP‐1 [7‐36 amide] or [7‐37] (1 pmol kg−1min−1) were infused intravenously over 4 h in fasted subjects. Plasma glucose (glucose‐oxidase), insulin and C‐peptide (ELISA) was measured during infusion and for 4 h thereafter. Indirect calorimetry was performed. Fasting hyperglycaemia was 11.7 ± 0.9 [7‐36 amide] and 11.3 ± 0.9 mmol l−1 [7‐37]. GLP‐1 infusions stimulated insulin secretion approximately 3‐fold (insulin peak 168 ± 32 and 156 ± 47 pmol l−1, p < 0.0001 vs basal; C‐peptide peak 2.32 ± 0.28 and 2.34 ± 0.43 nmol l−1, p < 0.0001, respectively, with GLP‐1 [7‐36 amide] and [7‐37]). Four hours of GLP‐1 infusion reduced plasma glucose (4.8 ± 0.4 and 4.6 ± 0.3 mmol l−1, p < 0.0001 vs basal values), and it remained in the non‐diabetic fasting range after a further 4 h (5.1 ± 0.4 and 5.3 ± 0.4 mmol l−1, for GLP [7‐36 amide] and [7‐37], respectively). There were no significant differences between GLP‐1 [7‐36 amide] and [7‐37] (glucose, p = 0.99; insulin, p = 0.99; C‐peptide, p = 0.99). Neither glucose oxidation nor lipid oxidation (or any other parameters determined by indirect calorimetry) changed during or after the administration of exogenous GLP‐1. In conclusion, GLP‐1 [7‐36 amide] and [7‐37] normalize fasting hyperglycaemia in Type 2 diabetic patients. Diabetes therapy (diet, sulphonyl ureas or metformin) does not appear to influence this effect. In fasting and resting patients, the effect persists during administration of GLP‐1 and for at least 4 h thereafter, without rebound. Significant changes in circulating substrate concentrations (e.g. glucose) are not accompanied by changes in intracellular substrate metabolism. © 1998 John Wiley & Sons, Ltd.