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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how glucagon, a hormone, affects blood sugar levels during fasting, particularly in individuals with prediabetes. Researchers aim to understand how glucagon and insulin, another hormone, work together to regulate fasting blood sugar. Participants will receive either a glucagon infusion or a glucose infusion that mimics their usual blood sugar levels. Suitable candidates have normal or slightly elevated fasting blood sugar and are not on medication for it. As an unphased trial, this study provides a unique opportunity to contribute to the scientific understanding of blood sugar regulation.

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.

Is there any evidence suggesting that glucagon is likely to be safe for humans?

Studies have shown that glucagon is generally safe for people. For example, small doses of glucagon have been safely used in children and adults with type 1 diabetes to prevent low blood sugar during exercise. In these cases, researchers reported no major safety issues, suggesting it is safe for humans.

Additionally, a new type of glucagon called dasiglucagon quickly and effectively treated low blood sugar in adults, with safety similar to other glucagon treatments. This suggests that glucagon is a safe option, even in different forms.

Overall, research indicates that glucagon treatments are usually safe with manageable side effects. However, as with any treatment, individual experiences can vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for prediabetes focus on lifestyle changes and medications like metformin to improve insulin sensitivity and lower blood sugar levels. However, this treatment stands out because it uses glucagon, a hormone typically involved in raising blood sugar, in a novel way. Researchers are excited because the glucagon infusion is administered at varying rates over a short period, potentially offering a new mechanism to regulate blood sugar levels differently than traditional therapies. This approach could pave the way for innovative management of prediabetes, offering new hope for patients who do not respond well to current treatments.

What evidence suggests that glucagon might be an effective treatment for prediabetes?

Research has shown that glucagon effectively raises blood sugar levels. In some studies, glucagon treatment increased blood sugar by at least 20 mg/dL from a low point. Another study found that glucagon helped patients quickly recover their blood sugar levels, often within 15 minutes. In this trial, participants will receive either a glucagon infusion or a glucose infusion as a placebo comparator. These findings suggest that glucagon could be useful for managing blood sugar levels, which is important in addressing prediabetes. Although glucagon is mainly known for treating low blood sugar, its ability to control glucose makes it worth studying further for managing prediabetes. ^{1 3 5 6 7}

Who Is on the Research Team?

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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, 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12368384/

Low-Dose Glucagon to Prevent and Treat Exercise ... The meta-analysis showed significant reductions in hypoglycemia risk (risk ratio 0.54; 95% CI 0.35, 0.84) and TBR (−3.91 percentage points; 95% ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7666610/

Glucagon Therapy: A Comparison of Current and Novel ... Treatment success was defined as an increase in plasma glucose levels to ≥70 mg/dL or an increase of ≥20 mg/dL in plasma glucose from the nadir within 30 ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2840793

Prescribing Trends of GLP-1 Receptor Agonists for Type 2 ... Research has highlighted the benefits of glucagon-like peptide 1 receptor agonists (GLP-1RAs) in managing blood glucose and reducing weight ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01994746

NCT01994746 | Efficacy and Safety of Nasal Glucagon for ... Study Details | NCT01994746 | Efficacy and Safety of Nasal Glucagon for Treatment of Hypoglycemia in Adults | ClinicalTrials.gov.

5. diabetesjournals.org diabetesjournals.org/care/article/44/6/1361/138706/Dasiglucagon-A-Next-Generation-Glucagon-Analog-for

Dasiglucagon—A Next-Generation Glucagon Analog for ... In the dasiglucagon group, plasma glucose recovery was achieved within 15 min in all but one participant (99%), superior to placebo (2%; P < ...

6. diabetesjournals.org diabetesjournals.org/care/article/48/5/846/158048/Cardiovascular-and-Kidney-Outcomes-and-Mortality

Cardiovascular and Kidney Outcomes and Mortality With Long ... Safety outcomes included total serious adverse events, discontinuation due to adverse events, severe hypoglycemia, retinopathy, pancreatitis, ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10913376/

Nasal Glucagon Reverses Insulin-induced Hypoglycemia ... The results indicate that NG has a lower risk of rebound hyperglycemia compared with that of IG. The proportion of patients who had a blood glucose level in the ...