NCT06976619

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

The Effect of Glycemic Control and of GLP-1 Receptor Agonism on Islet GLP-1 in People

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 25 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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

• Type 1 Diabetes
• Type 2 Diabetes

Interventions

Type	Name	Description
DRUG	Liraglutide Pen Injector	Liraglutide 0.6mg
OTHER	Saline Injections	Saline in syringes to serve as placebo for single blind study

Timeline

• Start date: 2025-10-03
• Primary completion: 2028-10-30
• Completion: 2029-03-31
• First posted: 2025-05-16
• Last updated: 2025-10-14

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study