Recruiting
Phase 2

GLP-1R Blockade

Sponsor:

Mayo Clinic

Code:

NCT06967558

Conditions

PreDiabetes

Eligibility Criteria

Sex: All

Age: 25 - 70

Healthy Volunteers: Accepted

Interventions

Exendin 9-39

Saline

Study Details

Brief summary:

We 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. At present it is unknown if these abnormalities develop in prediabetes and whether they contribute to the phenotypes observed. In this experiment we will use blockade of GLP1R to probe the contribution of endogenous GLP-1 secretion to the regulation of fasting glucose and islet function in prediabetes.

Conditions

PreDiabetes

Study ID

NCT06967558

Start date

Nov 1, 2025

Status verified date

Dec, 2025

Completion date

Mar 31, 2028

Anticipated

Primary completion date

Oct 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 25 - 70

Healthy Volunteers: Accepted

Inclusion Criteria:

  • People with stable weight and no history of diabetes.
  • Fasting glucose < 126 mg/dL
  • 2hr glucose after 75g OGTT < 200 mg/dL

Exclusion Criteria:

  • Age < 25 or > 70 years (to avoid studying subjects who could have latent type 1 diabetes, or the effects of age extremes in subjects with normal or impaired fasting glucose).
  • HbA1c > 6.5%
  • Use of any glucose-lowering agents including metformin or sulfonylureas.
  • For female subjects: positive pregnancy test at the time of enrollment or study
  • History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
  • Active systemic illness or malignancy.
  • Symptomatic macrovascular or microvascular disease.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

active comparator: Exendin 9-39

Subjects will receive exendin 9-39 during the study

placebo comparator: Saline

Subjects will receive saline during the study

Interventions

Exendin 9-39

Exendin 9-39 is a competitive antagonist of the GLP-1 receptor

Saline

Saline

Primary outcome measure

  • Alpha-cell responsivity to glucose as measured by G50 [ Time Frame: 0-240 minutes ]
  • Beta-cell responsivity to glucose [ Time Frame: 0-240 minutes ]

Central Contacts and Locations

Central contacts

Adrian Vella, MD

507-255-6515vella.adrian@mayo.edu

Locations

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

Amy O'Byrne

507-255-8547OByrne.Amy14@mayo.edu

Principal Investigator:

Adrian Vella

More Information

Sponsor

Mayo Clinic

Last update posted

Dec 15, 2025

Last verified

Dec, 2025

Keywords

  • Impaired Fasting Glucose
  • Impaired Glucose Tolerance
  • GLP-1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2025-12-15.