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.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: GLP-1 receptor agonist

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tao Wang, Ph.D; Phone Number: 0086-13815344640; Email: misswt2011@126.com
• Study Contact Backup: Name: Xiaoxing Yin, Ph.D; Phone Number: 0086-516-83372005; Email: yinxx@xzmc.edu.cn

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Recruiting
      • Department of Endocrinology
      • Contact: Hongwei Ling, MD; Phone Number: 0086-516-85806335; Email: linghongwei@medmail.com.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLP-1 RA therapy; GLP-1 RA was injected subcutaneously at standard dose and frequency for consecutive 6 months.	Drug: GLP-1 receptor agonist; GLP-1 RA was injected subcutaneously at standard dose and frequency for consecutive 6 months in patients with T2DM; Other Names: GLP-1 analogues

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline HbA1c at 1 month	In order to observe the change from baseline HbA1c at 1 month after GLP-1 RA treatment	1 month after GLP-1 RA treatment
Change from baseline FPG at 1 month	In order to observe the change from baseline FPG at 1 month after GLP-1 RA treatment	1 month after GLP-1 RA treatment
Change from baseline PPG at 1 month	In order to observe the change from baseline PPG at 1 month after GLP-1 RA treatment	1 month after GLP-1 RA treatment
Change from baseline serum lipids at 1 month	In order to observe the change from baseline serum lipids at 1 month after GLP-1 RA treatment	1 month after GLP-1 RA treatment
Change from baseline HbA1c at 3 month	In order to observe the change from baseline HbA1c at 3 month after GLP-1 RA treatment	3 month after GLP-1 RA treatment
Change from baseline FPG at 3 month	In order to observe the change from baseline FPG at 3 month after GLP-1 RA treatment	3 month after GLP-1 RA treatment
Change from baseline PPG at 3 month	In order to observe the change from baseline PPG at 3 month after GLP-1 RA treatment	3 month after GLP-1 RA treatment
Change from baseline serum lipids at 3 month	In order to observe the change from baseline serum lipids at 3 month after GLP-1 RA treatment	3 month after GLP-1 RA treatment
Change from baseline HbA1c at 6 month	In order to observe the change from baseline HbA1c at 6 month after GLP-1 RA treatment	6 month after GLP-1 RA treatment
Change from baseline FPG at 6 month	In order to observe the change from baseline FPG at 6 month after GLP-1 RA treatment	6 month after GLP-1 RA treatment
Change from baseline PPG at 6 month	In order to observe the change from baseline PPG at 6 month after GLP-1 RA treatment	6 month after GLP-1 RA treatment
Change from baseline serum lipids at 6 month	In order to observe the change from baseline serum lipids at 6 month after GLP-1 RA treatment	6 month after GLP-1 RA treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence and severity of possible adverse reaction within 1 month after GLP-1 RA treatment	To evaluate the incidence and severity of possible adverse reaction within 1 month after GLP-1 RA treatment, including gastrointestinal reaction and hypoglycemia	1 month after GLP-1 RA treatment
incidence and severity of possible adverse reaction within 3 month after GLP-1 RA treatment	To evaluate the incidence and severity of possible adverse reaction within 3 month after GLP-1 RA treatment, including gastrointestinal reaction and hypoglycemia	3 month after GLP-1 RA treatment
incidence and severity of possible adverse reaction within 6 month after GLP-1 RA treatment	To evaluate the incidence and severity of possible adverse reaction within 6 month after GLP-1 RA treatment, including gastrointestinal reaction and hypoglycemia	6 month after GLP-1 RA treatment

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Xuzhou Medical University
• Investigators: Study Director: Renhao Wang, Ph.D, The Affiliated Hospital of Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2019
• Primary Completion (Estimated): January 1, 2024
• Study Completion (Estimated): August 1, 2024

Study Registration Dates

• First Submitted: August 27, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 8, 2021

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 24, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: T2DM; GLP-1 RA; gene polymorphism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon-Like Peptide 1
• Other Study ID Numbers: XYFY2018-KL085

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No