Endogenous GLP-1 Secretion on Islet Function in People With and Without Type 2 Diabetes

NCT04466618 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 20-003993R01DK126206
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

GLP-1 is a hormone made by the body that promotes the production of insulin in response to GLP-1 is produced within the islets expressing prohormone convertase 1/3eating. However, there is increasing evidence that this hormone might help support the body's ability to produce insulin when diabetes develops. The purpose of this study is to determine the effect of endogenous GLP-1 secretion on insulin secretion in people with and without type 2 diabetes.

Conditions

Healthy; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change in Fasting Glucagon in the Presence or Absence of Exendin-9,39

  Concentrations of glucagon Measured by immunoassay over the -30 to 0 minutes of study. On one study day subjects received saline, on the other exendin-9,39. The infusion commenced at -120 minutes.

  Average concentration over the -30 to 0 minutes of study

Study Arms (4)

Saline

PLACEBO COMPARATOR

Saline infusion

Biological: Saline

Exendin-9,39

ACTIVE COMPARATOR

Exendin-9,39 infusion

Biological: Exendin-9,39

Saline + Intralipid/Heparin

ACTIVE COMPARATOR

Induction of acute insulin resistance during Saline infusion

Biological: Saline + Intralipid/Heparin

Exendin-9,39 + Intralipid/Heparin

ACTIVE COMPARATOR

Induction of acute insulin resistance during Exendin-9,39 infusion

Biological: Exendin-9,39 + Intralipid/Heparin

Interventions

Saline BIOLOGICAL

Saline infused during the study

Saline

Exendin-9,39 BIOLOGICAL

Exendin-9,39 infused during the study

Exendin-9,39

Saline + Intralipid/Heparin BIOLOGICAL

Saline infused during acute insulin resistance

Saline + Intralipid/Heparin

Exendin-9,39 + Intralipid/Heparin BIOLOGICAL

Exendin-9,39 infused during acute insulin resistance

Exendin-9,39 + Intralipid/Heparin

Eligibility Criteria

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

You may qualify if:

• Weight-stable, non-diabetic subjects

You may not qualify if:

• Age \< 25 or \> 65 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 glucose-lowering agents.
• 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.
• Weight-stable, diabetic subjects treated with diet and lifestyle alone or with metformin monotherapy
• Age \< 25 or \> 65 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).
• Use of any glucose-lowering agent other than metformin.
• or more fasting glucose values \> 250mg/dl on medication or after medication withdrawal.
• Unwillingness or inability to withdraw medication for three weeks prior to, and for the duration of the study.
• 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.

Sponsors & Collaborators

• Adrian Vella: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Welch AA, Farahani RA, Egan AM, Laurenti MC, Zeini M, Vella M, Bailey KR, Cobelli C, Dalla Man C, Matveyenko A, Vella A. Glucagon-like peptide-1 receptor blockade impairs islet secretion and glucose metabolism in humans. J Clin Invest. 2023 Nov 15;133(22):e173495. doi: 10.1172/JCI173495.

  PMID: 37751301 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sodium Chloride; soybean oil, phospholipid emulsion; Heparin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Dr Adrian Vella
• Organization: Mayo Clinic

vella.adrian@mayo.edu

5072843754

Study Officials

• Adrian Vella

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 10, 2020
• Study Start: April 15, 2021
• Primary Completion: December 15, 2022
• Study Completion: December 31, 2022
• Last Updated: December 26, 2023
• Results First Posted: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)