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

NCT06976619 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-007682
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Type 1 Diabetes; Type 2 Diabetes

Keywords

Islet Function; Glucose Toxicity

Outcome Measures

Primary Outcomes (2)

• Effect of exendin 9-39 on fasting glucagon secretion rate before and after liraglutide treatment

  Glucagon secretion rate will be estimated by deconvolution from glucagon concentrations during fasting (-30 to 0 min) of each study day.

  The change in fasting glucagon secretion rate (saline vs. exendin 9-39) in the baseline study will be compared with the change in fasting glucagon secretion rate (saline vs. exendin 9-39) after 30 days of treatment with liraglutide (post-liraglutide)

• Effect of exendin 9-39 on glucagon secretion rate during hyperglycemia before and after liraglutide

  Glucagon secretion rate will be estimated by deconvolution from glucagon concentrations during hyperglycemia (150 to 180 min) of each study day.

  The change in glucagon secretion rate during hyperglycemia (saline vs. exendin 9-39) in the baseline study will be compared with the change (saline vs. exendin 9-39) after 30 days of treatment with liraglutide (post-liraglutide)

Secondary Outcomes (2)

• Effect of exendin 9-39 on fasting glucagon secretion rate in people with type 1 diabetes vs type 2 diabetes

  The change in fasting glucagon secretion (saline vs. exendin 9-39) in the baseline studies will be compared in people with type 1 diabetes vs type 2 diabetes

• Effect of exendin 9-39 on glucagon secretion rate during hyperglycemia in people with type 1 diabetes vs type 2 diabetes

  The change in glucagon secretion during hyperglycemia (saline vs. exendin 9-39) in the baseline studies will be compared in people with type 1 diabetes vs type 2 diabetes

Study Arms (4)

Type 1 diabetes - Placebo arm

PLACEBO COMPARATOR

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

Other: Saline Injections

Type 1 diabetes - Liraglutide arm

ACTIVE COMPARATOR

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

Drug: Liraglutide Pen Injector

Type 2 diabetes - Placebo arm

PLACEBO COMPARATOR

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

Other: Saline Injections

Type 2 diabetes - Liraglutide arm

ACTIVE COMPARATOR

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

Drug: Liraglutide Pen Injector

Interventions

Liraglutide Pen Injector DRUG

Liraglutide 0.6mg

Also known as: Liraglutide

Type 1 diabetes - Liraglutide arm; Type 2 diabetes - Liraglutide arm

Saline Injections OTHER

Saline in syringes to serve as placebo for single blind study

Also known as: Placebo

Type 1 diabetes - Placebo arm; Type 2 diabetes - Placebo arm

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 1 or type 2 diabetes treated with insulin

You may not qualify if:

• Age \< 25 or \> 70 years.
• HbA1c \> 10.0%
• 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.
• Prior use of GLP-1 receptor agonists in the previous year.
• 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

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2

Interventions

Liraglutide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

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: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 16, 2025
• Study Start: October 3, 2025
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)