GLP-1 Receptor Blockade for Diabetes

Overseen By Adrian Vella, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Glucose-lowering agents

Disqualifiers: Age < 25 or > 70, Pregnancy, Upper abdominal surgery, Systemic illness, Macrovascular disease, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 1 week

80 Participants Needed

Trial Summary

What is the purpose of this trial?

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. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.

Research Team

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for individuals with a specific genetic risk (T-allele at rs7903146) that increases the chance of developing type 2 diabetes. It's focused on understanding how their bodies produce a hormone called GLP-1 in the pancreas.

Inclusion Criteria

My genetic test shows I have the TT or CC genotype.

Exclusion Criteria

I have the CT genotype for rs7903146.

HbA1c > 6.5%

I am not pregnant at the time of joining the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Exendin 9-39 or saline infusion during fasting and hyperglycemic clamp

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exendin 9-39

Trial Overview The study tests how blocking the GLP-1 receptor with Exendin 9-39 affects pancreatic function compared to a saline solution, especially in those at high genetic risk for type 2 diabetes.

Participant Groups

Group I: Exendin 9-39 Active Control 1 Intervention

Exendin 9-39 will be infused during fasting and during a hyperglycemic clamp

Group II: Saline Placebo Group 1 Intervention

Saline will be infused during fasting and during a hyperglycemic clamp

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+