Pharmacogenetics of Response to GLP1R Agonists
University of Maryland, Baltimore
Summary
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.
Description
Overweight/obese otherwise healthy volunteers will be recruited from the Old Order Amish population in Lancaster County, PA. In order to assess pharmacodynamic responses, research participants will undergo two frequently sampled intravenous glucose tolerance tests (FSIGT). The first FSIGT will be conducted at baseline prior to administration of drug. The second FSIGT will be conducted after six weeks of treatment with semaglutide (0.25 mg/wk X 4 wks; 0.5 mg/sk X 2 wks). The proposal proposes two specific aims: * Specific Aim #1. To identify genetic variants associated with effects of a GLP1R…
Eligibility
- Age range
- 18–89 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: * BMI greater than or equal to 27 kg/m2 * Of Amish Descent Exclusion Criteria: * Woman of childbearing age who is sexually active * History of diabetes (HbA1c \> 6.5% or random glucose \>200 mg/dL) * Known allergy to semaglutide * Medical issues, which in the judgment of the research physician or PIs might increase the risk associated with participation in the study * eGFR \< 60 mL/min/1.73 sq. m. * Hematocrit \< 35% * TSH \< 0.4 o4 \> 5.5 * AST or ALT in excess of 2X the upper limit of normal * Unable to discontinue a drug, vitamin, or nutritional supplement, which in t…
Interventions
- DrugSemaglutide Pen Injector [Ozempic]
Participants will receive subcutaneously injected semaglutide (0.25 mg/wk) for 4 weeks followed by semaglutide (0.5 mg/wk) for an additional two weeks.
Location
- Amish Research ClinicLancaster, Pennsylvania