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

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2021 · $711,461

## Abstract

ABSTRACT
This clinical trial will uncover new mechanisms of inter-individual responses to endogenous and exogenous
glucagon-like peptide-1 (GLP-1) in Hispanics/Latinos (H/Ls) with prediabetes. The results move the
management of prediabetes, type 2 diabetes mellitus (T2DM), and relevant metabolic diseases to a more
individualized approach in an understudied and at-risk population. Few options exist for prediabetes treatment,
and the current pharmaceutical management of T2DM does not predict drug treatment failures, nor differences
in individual treatment responses and adverse effects. A precise, genetics-based approach will provide superior
therapeutic management for patients. GLP-1-based therapies reduce blood glucose, promote weight loss,
decrease cardiovascular events, and improve renal function. Prior genetic studies, most done in Caucasians,
identified associations between genetic variants and decreased GLP-1-induced insulin secretion, in an effort to
guide individualized treatment. However, these associations do not provide a clear mechanistic relationship
between genotype and phenotype. Transcriptomic analyses will uncover many of these mechanisms. Here, we
propose to 1) test the association of single nucleotide polymorphisms (SNPs) that regulate expression (eQTLs)
of 11 candidate genes in a range of relevant metabolic tissues with differential GLP-1 response, 2) perform RNA
sequencing before and after treatment to identify eQTLs in blood that predict response to GLP-1 therapy and
develop risk-based prediction models in H/Ls, and 3) determine the effects of genetic regulation of candidate
genes and newly discovered eQTLs phenome-wide in a large existing biobank, BioVU. For aims 1 and 2,
responses will be measured in 300 study subjects with prediabetes recruited from an established Mexican-
American cohort via the oral minimal model method, before and after GLP-1 therapy, quantifying GLP-1
hormone efficacy and GLP-1-induced pancreatic beta cell insulin release and peripheral insulin sensitivity.
Procedures include serial measurements of plasma glucose, insulin, C-peptide, and GLP-1, and peripheral blood
collection for RNA sequencing. Our central hypotheses are: (1) metabolic tissue-based eQTLs of GLP-1-
associated genes will be associated with physiological response to endogenous and exogenous GLP-1,
(2) identification of eQTLs associated with GLP-1 treatment-induced changes in whole blood will identify new
gene targets, and (3) this data will lead to the creation of eQTL-based prediction models for related diseases.
The study is innovative because it uses a novel combination of eQTL analysis and oral minimal model to assess
GLP-1 response, examines a population highly underrepresented in pharmacogenomic studies, and utilizes
novel statistical methods and applications to study gene expression. The significance of this newly acquired
mechanistic information will ultimately guide precision therapeutic regimens for diabetes prevention and
treat...

## Key facts

- **NIH application ID:** 10299488
- **Project number:** 1R01DK127084-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** Absalon Dennis Gutierrez
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $711,461
- **Award type:** 1
- **Project period:** 2021-07-09 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10299488

## Citation

> US National Institutes of Health, RePORTER application 10299488, Pharmacogenetics of the Response to GLP-1 in Mexican-Americans with Prediabetes (1R01DK127084-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10299488. Licensed CC0.

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