Subcutaneous glucagon-like peptide-I (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released p ostprandially that stimulates insulin secretion, suppresses glucagon secret ion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published stud ies have in dicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-depe ndent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to im prove glycaemic control in early Type 2 diabetes, is insulinotropic at normal fas ting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or sari ne subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also e xamined. 3, GLP-1 caused a near 5-fold rise in plasma insulin concentration. After t reatment with GLP-1, circulating plasma glucose concentrations fell below t he normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred wit h GLP-1 injection which was seen at the same time as the rise in plasma GLP -1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal hom oeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.