Pharmacogenetics of the Response to GLP-1 in Mexican-Americans With Prediabetes

NCT05119179 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: HSC-MS-21-02975R01DK127084
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

This project uses both transcriptomic- and genomic-level data to identify mechanisms of individual responses to glucagon-like peptide-1 (GLP-1) in Mexican-Americans with prediabetes. The GLP-1 hormone is essential for glucose reduction, weight loss, cardiovascular risk reduction, and renal protection. Newly discovered mechanisms will illuminate causal links between disease genotype and phenotype, which may ultimately guide personalized therapeutic approaches for type 2 diabetes, prediabetes, obesity, cardiovascular disease, renal disease, and other related diseases.

Conditions

PreDiabetes

Keywords

prediabetes; Mexican-American; GLP-1; pharmacogenetics; expression quantitative trait loci

Outcome Measures

Primary Outcomes (17)

• Mean change in beta cell responsivity

  A rate which measures the ability of beta cells to secrete insulin

  12 weeks

• Insulin Sensitivity

  Measurement of the efficacy of insulin action at peripheral tissues

  12 weeks

• Disposition Index

  Product of beta cell responsivity and insulin sensitivity (see above)

  12 weeks

• GLP-1-Induced Potentiation

  Measurement of GLP-1 (glucagon-like peptide 1) hormonal efficacy in relationship to postprandial insulin secretion

  12 weeks

• Mean change in GLP-1 Area Under the Curve (AUC)

  Comparison of GLP-1 AUC measurements before and after drug intervention

  12 weeks

• Gene expression changes for minor variants of eQTLs for TCF7L2

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for KCNQ1

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for WFS1

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for THADA

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for CNR1

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for CTRB1

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for CTRB2

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for GLP1R

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for CHST3

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for MTNR1B

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Gene expression changes for minor variants of eQTLs for SORCS1

  eQTLs (expresion quantitative trait loci) are genes which affect the mRNA expression of another target gene.

  12 weeks

• Previously unidentified cis-eQTLs associated with change in gene expression due to GLP-1 challenge

  Study has statistical power to detect previously unidentified eQTLs

  12 weeks

Secondary Outcomes (6)

• Mean change in glucose Area Under the Curve (AUC)

  12 weeks

• Mean change in C-peptide Area Under the Curve (AUC)

  12 weeks

• Change in hemoglobin A1C

  12 weeks

• Mean change in insulin Area Under the Curve (AUC)

  12 weeks

• Creation of eQTL-based disease prediction models

  5 years

Study Arms (1)

Semaglutide

EXPERIMENTAL

Semaglutide 0.25 mg subcutaneously weekly for 4 weeks, followed by semaglutide 0.5 mg subcutaneously weekly for 8 weeks.

Drug: Semaglutide

Interventions

Semaglutide DRUG

Glucagon-like Peptide 1 Receptor Agonist

Also known as: Ozempic

Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women, ages 18 years and older
• Diagnosis of Prediabetes - defined as either impaired fasting glucose (fasting glucose of 100-125 mg/dL), impaired glucose tolerance (2-hour postprandial blood glucose of 140-199 mg/dL after 75-gram oral glucose challenge), and/or a hemoglobin A1C ranging from 5.7% to 6.4%
• High risk for progression to diabetes: defined as having at least one of the two following additional factors: Obesity (BMI ≥ 30 kg/m2) and/or metabolically unhealthy status. "Metabolically unhealthy status" is defined as at least two of the following: elevated blood pressure (SBP ≥ 130 mmHg and/or DBP ≥ 85 mmHg), elevated triglycerides ≥ 150 mg/dL, low HDL cholesterol (males \< 40 mg/dL; females \< 50 mg/dL), and elevated fasting glucose ≥ 100 mg/dL (Wu S et al., 2017).
• Women of childbearing age must agree to use an acceptable method of pregnancy prevention (barrier methods, abstinence, hormonal contraception, intrauterine contraception, or surgical sterilization) for the duration of the study.
• Patients must have the following laboratory values: Hematocrit ≥ 34 vol%, estimated glomerular filtration rate ≥ 60 mL/min per 1.73 m2, AST (SGOT) \< 2.5 times ULN, ALT (SGPT) \< 2.5 times ULN, alkaline phosphatase \< 2.5 times ULN

You may not qualify if:

• History of Type 1 or Type 2 diabetes mellitus
• Pregnant or breastfeeding women
• Medications: metformin, DPP-4 inhibitors, GLP-1 receptor agonists, SGLT-2 inhibitors, thiazolidinediones, insulin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, and/or corticosteroids over the last 3 months.
• Active malignancy
• History of clinically significant cardiac, hepatic, pancreatic or renal disease.
• History of any serious hypersensitivity reaction to the study medication (or any other incretin mimetic)
• Prisoners or subjects who are involuntarily incarcerated
• Prior history of pancreatitis, medullary thyroid cancer, or multiple endocrine neoplasia type 2 (MEN 2)
• Family history of medullary thyroid cancer (a rare form of thyroid cancer) or MEN2. However, as many individuals may not be aware of the specific type of thyroid cancer, will also exclude any family history of thyroid cancer or MEN2.
• Hospitalization for COVID-19 in last 3 months

Sponsors & Collaborators

• Vanderbilt University Medical Center: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

UTHealth Clinical Research Unit (CRU) at UT Brownsville

Brownsville, Texas, 78520, United States

RECRUITING

MeSH Terms

Conditions

Prediabetic State

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Absalon D Gutierrez, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Norma Perez-Olazaran

CONTACT

(956) 755-0695; Norma.P.PerezOlazaran@uth.tmc.edu

Rocio Uribe

CONTACT

(956) 882-5165; Rocio.D.Uribe@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Model Details: Single center, before and after clinical trial

Study Record Dates

• First Submitted: August 5, 2021
• First Posted: November 15, 2021
• Study Start: November 22, 2021
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)