Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish
population in Lancaster County, PA. Lancaster County, PA. Pharmacodynamic responses to GLP1R
agonist will be assessed by conducting frequently sampled intravenous glucose tolerance tests
(FSIGT) both before and after semaglutide for six weeks. The proposal proposes two specific
aims:
1. Specific Aim #1. To identify genetic variants associated with effects of a GLP1R agonist
to enhance glucose-stimulated first phase insulin secretion in the two FSIGTs (before
and after administration of drug).
2. Specific Aim #2. To identify genetic variants associated with the effect of a GLP1R
agonist to accelerate the rate of glucose disappearance as assessed in the two FSIGTs
(before and after administration of drug).
Genotyping will be conducted using a high-density array with comprehensive coverage of DNA
sequence variants. In addition, the analysis will leverage a global imputation panel
generated from 1,025 Amish individuals.