Pharmacogenetics of Response to GLP1R Agonists

ConditionsObesity Diabetes Type 2

Trial statusRecruiting

Trial phasePhase 1

Trial typeInterventional

Biological sexAll

Age18-89

SponsorUniversity of Maryland, Baltimore

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

BMI greater than or equal to 27 kg/m2

Of Amish Descent

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Semaglutide Pen Injector [Ozempic]
Drug
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.

Treatment groups

600 Participants

are divided into 1 treatment group

Group A: Open label administration of semaglutideExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

First phase insulin secretion

Area under the curve for plasma insulin levels measured at times between 0-10 min after administration of intravenous glucose (0.3 g/kg)

Time frame

Measured both at baseline and after completing 6 weeks of semaglutide therapy

Second phase insulin secretion

Area under the curve for plasma insulin levels measured at times between 10-50 min after administration of intravenous glucose (0.3 g/kg)

Time frame

Measured both at baseline and after completing 6 weeks of semaglutide therapy

Rate of glucose disappearance

Slope of the plot of log(glucose concentration) as a function of time. This will be calculated based on a linear regression using data points between 25-50 minutes after administration of intravenous glucose (0.3 g/kg)

Time frame

Measured both at baseline and after completing 6 weeks of semaglutide therapy

Secondary outcomes

Weight loss

This will be measured as the baseline weight in kg minus the weight after completing 6 weeks of semaglutide therapy.

Time frame

Assessed after completing 6 weeks of semaglutide therapy

Other outcomes

Insulin sensitivity (Si)

Estimated using Bergman's minimal model

Time frame

Measured both at baseline and after completing 6 weeks of semaglutide therapy

Glucose effectiveness (Sg)

Estimated using Bergman's minimal model

Time frame

Measured both at baseline and after completing 6 weeks of semaglutide therapy

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Maryland, Baltimore

Lead sponsor

Source ClinicalTrials.gov

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