Pharmacogenomics of GLP1 Receptor Agonists

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests (FSIGT) - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). Based on data obtained from the FSIGT, participants' response to exenatide was assessed -- specifically, the effect of exenatide to enhance insulin secretion and accelerate metabolism of glucose. The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.