The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People With Type 1 and Type 2 Diabetes

NCT ID: NCT06976619

Last Updated: 2025-10-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-03

Study Completion Date

2029-03-31

Brief Summary

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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. There is evidence that α-cell proglucagon processing is subject to paracrine regulation by the β-cell3. It is unclear if the effects of GLP1R agonism on islet GLP-1 differ in Type 1 diabetes (T1DM) compared to T2DM. This experiment will examine the effect of glycemic control ± a GLP1R agonist on islet GLP-1 in people with (T2DM) and without (T1DM) β-cells.

Detailed Description

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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. This supports other evidence (rodents and humans) that through the (inducible) expression of a prohormone convertase (PC-1/3), the α-cell can process proglucagon to intact GLP-15,6. 'Islet' or 'pancreatic' GLP-1 acts in a paracrine fashion to regulate insulin (basal and 1st phase) and glucagon secretion. 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.

There is evidence that α-cell proglucagon processing is subject to paracrine regulation by the β-cell. β-cell secretion of the signaling peptide 14-3-3-Zeta is decreased by GLP1R agonism (Fig.1), stimulating α-cell production of GLP-1. This is a testable hypothesis in humans; people with type 1 diabetes (T1DM) have dysregulated glucagon secretion and evidence of islet GLP-1. It is unclear if the effects of GLP1R agonism on islet GLP-1 differ compared to T2DM. This experiment will examine the effect of glycemic control ± a GLP1R agonist on islet GLP-1 in people with (T2DM) and without (T1DM) β-cells.

Conditions

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Type 1 Diabetes Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

SINGLE

Participants
Intervention will be assigned in single-blind fashion (Placebo pens for liraglutide are unavailable). A placebo syringe created by Research Pharmacy in addition to 'masked' liraglutide pens will be used over 4-weeks

Study Groups

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Type 1 diabetes - Placebo arm

Subjects will receive syringes loaded with saline to self-administer daily during the intervention phase

Group Type PLACEBO_COMPARATOR

Saline Injections

Intervention Type OTHER

Saline in syringes to serve as placebo for single blind study

Type 1 diabetes - Liraglutide arm

Subjects will receive 0.6mg Liraglutide syringes to self-administer daily during the intervention phase

Group Type ACTIVE_COMPARATOR

Liraglutide Pen Injector

Intervention Type DRUG

Liraglutide 0.6mg

Type 2 diabetes - Placebo arm

Subjects will receive syringes loaded with saline to self-administer daily during the intervention phase

Group Type PLACEBO_COMPARATOR

Saline Injections

Intervention Type OTHER

Saline in syringes to serve as placebo for single blind study

Type 2 diabetes - Liraglutide arm

Subjects will receive 0.6mg Liraglutide syringes to self-administer daily during the intervention phase

Group Type ACTIVE_COMPARATOR

Liraglutide Pen Injector

Intervention Type DRUG

Liraglutide 0.6mg

Interventions

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Liraglutide Pen Injector

Liraglutide 0.6mg

Intervention Type DRUG

Saline Injections

Saline in syringes to serve as placebo for single blind study

Intervention Type OTHER

Other Intervention Names

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Liraglutide Placebo

Eligibility Criteria

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Inclusion Criteria

* Type 1 or type 2 diabetes treated with insulin

Exclusion Criteria

1. Age \< 25 or \> 70 years.
2. HbA1c \> 10.0%
3. For female subjects: positive pregnancy test at the time of enrollment or study
4. History of prior upper abdominal surgery such as adjustable gastric banding, pyloroplasty and vagotomy.
5. Prior use of GLP-1 receptor agonists in the previous year.
6. Active systemic illness or malignancy.
7. Symptomatic macrovascular or microvascular disease.
Minimum Eligible Age

25 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mayo Clinic

OTHER

Sponsor Role lead

Responsible Party

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Adrian Vella

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Adrian Vella, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

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Mayo Clinic in Rochester

Rochester, Minnesota, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Adrian Vella, MD

Role: CONTACT

507-255-6515

Facility Contacts

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Amy O'Byrne

Role: primary

507-255-8547

Other Identifiers

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24-007682

Identifier Type: -

Identifier Source: org_study_id

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