Abstract
Diabetes. Epub ahead of print 2 October 2013
Glucagon-like-peptide-1 (GLP-1) agonists are used in the treatment of type 2 diabetes due to their ability to lower blood glucose concentration by stimulating insulin secretion, suppressing glucagon secretion and slowing gastric emptying. The aim of this study was to determine whether tachyphylaxis to the effect of GLP-1 on gastric emptying occurs rapidly and whether it affects postprandial glycaemia. The authors hypothesized that intermittent administration of GLP-1 would slow gastric emptying more than prolonged continuous administration.
Ten healthy males attended hospital following an overnight fast on two separate occasions and were assigned to regimens A and B in a randomized double-blind fashion. Regimen A assessed the response to ‘acute’ and ‘intermittent’ administration of GLP-1 and regimen B assessed the response to ‘placebo’ and ‘prolonged’ GLP-1 exposure. A radioisotope labelled meal was used to assess gastric emptying and the time taken for the stomach to empty 50% (T50) was calculated. Blood samples were taken for the measurement of glucose and insulin and to enable the calculation of postprandial glycaemia and insulinaemia.
All GLP-1 infusions slowed gastric emptying compared to the placebo (P < 0.001), acute and intermittent infusions had similar effects and significantly increased gastric retention when compared to prolonged infusion. Postprandial glycaemia was reduced by intermittent GLP-1 infusion compared to prolonged (P = 0.007) infusion, but there was no difference between prolonged GLP-1 infusion and placebo (P = 0.21). Postprandial insulinaemia was significantly lower following intermittent GLP-1 infusion compared to prolonged GLP-1 infusion (P = 0.003).
The authors concluded that prolonged stimulation of the GLP-1 receptor markedly attenuates the magnitude of the slowing of gastric emptying and this reduces the effect of GLP-1 on postprandial glycaemic excursions, thus supporting their hypothesis of rapid tachyphylaxis.