The Role of Islet GLP-1 in the Pathogenesis of Prediabetes

NCT06967558 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-007677
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Impaired Fasting Glucose; Impaired Glucose Tolerance; GLP-1

Outcome Measures

Primary Outcomes (2)

• Alpha-cell responsivity to glucose as measured by G50

  The change in glucose necessary to suppress glucagon secretion by 50%

  0-240 minutes

• Beta-cell responsivity to glucose

  This is measured as the gradient of the increase in insulin secretion rate per unit increase in glucose concentration

  0-240 minutes

Study Arms (2)

Exendin 9-39

ACTIVE COMPARATOR

Subjects will receive exendin 9-39 during the study

Biological: Exendin 9-39

Saline

PLACEBO COMPARATOR

Subjects will receive saline during the study

Biological: Saline

Interventions

Exendin 9-39 BIOLOGICAL

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

Exendin 9-39

Saline BIOLOGICAL

Saline

Saline

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

MeSH Terms

Conditions

Prediabetic State; Glucose Intolerance

Interventions

exendin (9-39); Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Adrian Vella, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adrian Vella, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: we will study people with normal glucose tolerance with or without impaired fasting glucose together with people with impaired fasting glucose with or without impaired glucose tolerance. All subjects will be studied on 2 occasions - on one they will receive exendin 9-39 and on the other saline

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 13, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)