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The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans

NCT06972407 · Status: NOT_YET_RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 80

Last updated 2026-01-30

No results posted yet for this study

Summary

The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.

Conditions

  • Genetic Predisposition
  • Type2diabetes

Interventions

BIOLOGICAL

Exendin 9-39

A competitive antagonist of the GLP-1 receptor

OTHER

Saline

Saline infusion will serve as an inactive comparator

Sponsors & Collaborators

Principal Investigators

  • Adrian Vella, MD · Mayo Clinic

Study Design

Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Model
CROSSOVER

Eligibility

Min Age
25 Years
Max Age
70 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2026-10-01
Primary Completion
2028-12-31
Completion
2029-03-01
FDA Drug
Yes

Countries

  • United States

Study Locations

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Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06972407 on ClinicalTrials.gov