Effect of Gene Polymorphisms on GLP-1 Receptor Agonists Response in Patients With T2DM

Department of Pharmacy, the Affiliated Hospital of Xuzhou Medical University

1. This is an prospective study to evaluate the effect of gene polymorphisms on therapeutic responses to glucagon like peptide-1 receptor agonist (GLP-1 RA) in patients with T2DM.
2. T2DM patients and healthy subjects were recruited to identify genotypes and detect the level of T2DM susceptibility genes expression levels in the plasma of healthy participants and T2DM patients.
3. This is a retrospective cohort study of patients with T2DM who were treated with exenatide twice daily as a part of their diabetes care for at least 12 months.

Many guidelines recommend the preferential use of GLP-1 RA after single drug or multiple oral hypoglycemic drugs and basic insulin therapy for poor glycemic control. However, the clinical responsiveness to GLP-1 RA varies among patients with T2DM. It has been reported that genetic factors are the important reasons for individual variation in therapeutic response of antidiabetic drugs. At present, dozens of gene loci related to therapeutic response of antidiabetic drugs have been screened, which are of great clinical significance in guiding clinical individualized treatment, improving the efficacy and safety of drugs, and reducing the drug costs.

GLP-1 RA was injected subcutaneously at standard dose and frequency for consecutive 6 months. The patients were visited at moths 0, 3, and 6, and medical histories, physical examinations, and routine clinical laboratory tests were performed during these visits. The general anthropometric parameters considered for this study were height (m), weight (kg), and waist and hip circumferences (cm) at baseline, 3 months and 6months after exenatide treatment. After an overnight fast, venous blood samples were obtained both in the fasting state and 2 h later during a standard 75-g oral glucose tolerance test. Parameters were measured at baseline, the end of months 3 and 6 after administration of exenatide.

Peripheral blood was collected at follow-up and genomic DNA was extracted from peripheral blood leucocytes. We further explored the association of gene polymorphisms with the therapeutic effect of GLP-1 RA in patients with T2DM.

Inclusion Criteria:

1. a diagnosis of T2DM；
2. a body mass index (BMI) of 20-35 kg/m2；
3. an HbA1c of 7.0%-12%, an age of 25-70 years；
4. required data available at baseline, 3 months, and 6 months after GLP-1 RA therapy.

Exclusion Criteria:

1. Patients with serious diseases such as acute myocardial infarction, cerebral vascular accident, trauma, kidney or liver diseases, severe gastrointestinal dysfunction, and history of pancreatitis；
2. patients receiving GLP-1 analogues, weight loss drugs, glucocorticoids, drugs affecting gastrointestinal peristalsis in the past 3 months；
3. those with missing data at the time points of baseline, 3 months, and 6 months after GLP-1 RA therapy.