Glucagon for Prediabetes

Overseen By Jeanette Laugen

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Glucose-lowering agents

Disqualifiers: Pregnancy, Abdominal surgery, Active illness, others

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Fasting hyperglycemia contributes disproportionately to nonenzymatic glycosylation and the microvascular complications of type 2 diabetes. However, little is known about the regulation of glucose concentrations in the fasting state relative to what is known about the postprandial state. The proposed experiment is part of a series of experiments designed to establish how glucagon and insulin interact with their receptors to control fasting glucose in health and in prediabetes.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any glucose-lowering medications, such as metformin or sulfonylureas, to participate in this trial.

How is glucagon used for prediabetes different from other drugs?

Glucagon is unique because it is primarily known for its role in increasing blood sugar levels, unlike other treatments for prediabetes that focus on lowering blood sugar. This makes it distinct from GLP-1 analogues, which are used to enhance insulin secretion and reduce blood sugar levels in type 2 diabetes. ^{1 2 3 4 5}

Research Team

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for individuals who do not have type 2 diabetes but may be at risk (prediabetes). Participants should be interested in understanding how their body controls blood sugar levels when they haven't eaten (fasting state).

Inclusion Criteria

Individuals with normal or impaired fasting glucose and normal or impaired glucose tolerance

Exclusion Criteria

HbA1c less than 6.5%

I am taking medication to lower my blood sugar.

Positive pregnancy test for female subjects at the time of enrollment or study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glucagon or glucose infusion to study their effects on fasting insulin secretion and glucose metabolism

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Glucagon

Trial Overview The study is looking into the effects of glucagon, a hormone that raises blood sugar, on insulin secretion and glucose metabolism during fasting. It aims to better understand how these hormones interact in people without diabetes.

Participant Groups

Group I: Glucagon Infusion Active Control 1 Intervention

A glucagon infusion (0.2 ng/kg/min) will start at 0900 (0 min), increasing to 0.4 (1000), 0.6 (1100) and 0.8 ng/kg/min (1200) at 60-minute intervals - ending at 1300 (240 min).

Group II: Glucose Infusion Placebo Group 1 Intervention

At 0900 (0 min) a glucose infusion will commence, and the infusion rate varied to replicate (± 5mg/dL) that individual's glucose concentrations observed during the Glucagon Infusion Day. The experiment will end at 1300 (240 min) when infusions are stopped.

Glucagon is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as GlucaGen for:

• Hypoglycemia
• Diagnostic aid

Approved in United States as Glucagon for:

• Severe hypoglycemia
• Diagnostic aid

Approved in Canada as Glucagon Novo Nordisk for:

• Hypoglycemia
• Diagnostic aid

Approved in Japan as Glucagon Lilly for:

• Hypoglycemia
• Diagnostic aid

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Findings from Research

Proglucagon-derived peptides (PGDPs) like GLP-1 and glucagon play crucial roles in managing energy balance and blood glucose levels, with GLP-1 being particularly effective in treating type 2 diabetes by enhancing insulin secretion and reducing glucagon levels.

GLP-1 receptor agonists, such as exendin 4, have been approved for diabetes treatment, while dipeptidyl-peptidase-IV inhibitors are in phase III trials, showing promise in stabilizing GLP-1 levels and improving blood glucose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biologic actions and therapeutic potential of the proglucagon-derived peptides. Drucker, DJ.[2018]

GLP-1 analogues, such as exenatide and liraglutide, significantly improve glycemic control in type 2 diabetes patients, reducing HbA1c levels by about 1% compared to placebo, based on a review of 17 trials with 6899 participants.

These medications also promote weight loss and improve beta-cell function, although gastrointestinal side effects like nausea are common, particularly at the start of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus. Shyangdan, DS., Royle, P., Clar, C., et al.[2023]

GLP-1 is a hormone that enhances insulin secretion and has protective effects on pancreatic beta cells, making it a promising target for managing type-2 diabetes, especially since it only acts when blood sugar levels are high, reducing the risk of hypoglycemia.

While natural GLP-1 has a short half-life, various analogues have been developed for longer-lasting effects, although they require injections; research is ongoing for orally active small-molecule agonists that could provide a more convenient treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The class B G-protein-coupled GLP-1 receptor: an important target for the treatment of type-2 diabetes mellitus. Miller, LJ., Sexton, PM., Dong, M., et al.[2020]

The study synthesized various forms of glucagon-like peptide-I (GLP-I) to investigate how they bind to pancreatic beta cells, revealing that both the amino and carboxyl terminal domains are important for this binding.

Competitive binding experiments indicated that glucagon, while related, is a weak agonist for GLP-I binding, highlighting the specific role of GLP-I in stimulating insulin secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural requirements for biological activity of glucagon-like peptide-I. Mojsov, S.[2019]

GLP-1 analogues effectively lower HbA1c levels by about 1% in patients with type 2 diabetes who are not achieving satisfactory control with oral medications, based on a systematic review of 28 randomized controlled trials.

These medications also promote significant weight loss (between 2.3 to 5.5 kg) compared to other treatments, with a low incidence of hypoglycemia, making them a safe and effective option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis. Shyangdan, DS., Royle, PL., Clar, C., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Biologic actions and therapeutic potential of the proglucagon-derived peptides. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus. [2023]

3. England pubmed.ncbi.nlm.nih.gov

The class B G-protein-coupled GLP-1 receptor: an important target for the treatment of type-2 diabetes mellitus. [2020]

4. Denmark pubmed.ncbi.nlm.nih.gov

Structural requirements for biological activity of glucagon-like peptide-I. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide analogues for type 2 diabetes mellitus: systematic review and meta-analysis. [2022]