Pharmacogenomics of GLP1 Receptor Agonists

University of Maryland Baltimore (UMB)

Status and phase: Terminated; Phase 1

Conditions: Type 2 Diabetes

Treatments: Drug: Exenatide Injection (before the first FSIGT); Drug: Exenatide injection before the second FSIGT)

Study type: Interventional

Funder types: Other

Identifiers

NCT05762744

HP-00067574

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 63 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Member of the Old Order Amish community in Lancaster County, Pennsylvania
• BMI: 18-40 kg/sq.m.

Exclusion criteria

• Known allergy to exenatide
• History of diabetes, random glucose >200 mg/dL, or HbA1c > 6.5%
• Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation
• Seizure disorder
• Pregnant by self-report or known pregnancy within 3 months of the start of study
• Currently breast feeding or breast feeding within 3 months of the start of the study
• Estimated glomerular filtration rate <60 mL/min/1.73m2
• Hematocrit <35%
• Liver function tests greater than 2 times the upper limit of normal
• Abnormal thyroid stimulating hormone
• History of pancreatitis or pancreatic cancer. Personal or family history of medullary carcinoma of the thyroid.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Single Blind

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63 participants in 2 patient groups

Exenatide followed by saline

Other group

Description:

Participants were randomized to receive exenatide 15 min before the first frequently sampled iv glucose tolerance test and saline 15 min before the second frequently sampled iv glucose tolerance test

Treatment:

Drug: Exenatide Injection (before the first FSIGT)

Saline followed by exenatide

Other group

Description:

Participants were randomized to receive saline15 min before the first frequently sampled iv glucose tolerance test and exenatide15 min before the second frequently sampled iv glucose tolerance test

Treatment:

Drug: Exenatide injection before the second FSIGT)