Pharmacogenomics of GLP1 Receptor Agonists

Summary

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 - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). 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.

Timeline

Start

2016-06-01

Primary completion

2018-11-30

Completion

2022-10-31

Publications

• Background Taylor SI, Montasser ME, Yuen AH, Fan H, Yazdi ZS, Whitlatch HB, Mitchell BD, Shuldiner AR, Muniyappa R, Streeten EA, Beitelshees AL. Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness. Diabetes Obes Metab. 2023 Sep;25(9):2586-2594. doi: 10.1111/dom.15143. Epub 2023 Jun 1.
• Beitelshees AL, Streeten EA, Shahidzadeh Yazdi Z, Whitlatch HB, Mitchell BD, Shuldiner AR, Montasser ME, Taylor SI. Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test. Clin Transl Sci. 2024 May;17(5):e13809. doi: 10.1111/cts.13809.

Drugs

Indications