Glucagon for Obesity

(GIO Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

Must not be taking: Weight loss, antipsychotics

Disqualifiers: Diabetes, liver disease, cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

To further understand the tolerability of glucagon.

Do I need to stop my current medications to join the trial?

The trial requires that you have not taken any medication known to significantly impact body weight, like weight loss drugs or certain antipsychotics, within 3 months before screening. However, stable hormone replacement therapy is allowed. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

What evidence supports the effectiveness of the drug Glucagon for obesity?

Research on GLP-1, a hormone related to glucagon, shows it can help reduce body weight by promoting feelings of fullness and reducing appetite. While GLP-1 is used for type 2 diabetes, its weight loss effects suggest potential benefits for obesity treatment. ^{1 2 3 4 5}

Is glucagon safe for human use?

Glucagon is generally considered safe for human use, as it plays a natural role in regulating blood sugar levels. It has been used in various treatments, and while specific safety data for obesity is limited, its use in other conditions suggests it is well-tolerated. ^{6 7 8 9 10}

How does the drug glucagon differ from other obesity treatments?

Glucagon, used in this trial for obesity, is unique because it is a hormone that regulates energy balance and glucose levels, unlike other obesity treatments that may focus solely on appetite suppression or fat absorption. It works by interacting with specific receptors to control glucose production and reduce food intake, offering a novel approach compared to traditional weight loss drugs. ^{2 3 4 10 11}

Research Team

Steven R Smith, MD

Principal Investigator

Prinicipal Investigator

Eligibility Criteria

Adults aged 18-55 with a BMI between 27 and 40, non-diabetic, in good health without significant medical conditions. Participants must not have had weight fluctuations or surgery recently, avoid alcohol, caffeine, strenuous activity before visits, and if female and able to bear children, use birth control.

Inclusion Criteria

Subject is willing to avoid strenuous physical activity for 72 hours prior to the inpatient study visit

I am using or willing to use birth control during the study.

Stable body weight for 3 months (self-reported loss/gain <5%)

Exclusion Criteria

I have a serious heart condition.

I have anemia.

I have a metabolic, endocrine, or other similar disorder.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive glucagon infusion in an escalating manner at 12.5, 25, 37.5, and 50 ng/kg/min, each step for 60 minutes. Nausea intensity is assessed at 30 and 60 minutes of each infusion rate.

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 trial is testing the tolerability of glucagon infusions in obese individuals. It aims to understand how well these participants can tolerate this hormone treatment which could potentially influence body weight regulation.

Participant Groups

Group I: Glucagon Infusion Experimental Treatment 1 Intervention

Glucagon infusion in escalating manner at 12.5, 25, 37.5 and 50 ng/kg/min (each step for 60 min). At 30 and 60 mins of each infusion rate, we will administer a previously established questionnaire to assess overall nausea intensity.

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?

Translational Research Institute for Metabolism and Diabetes, Florida

Lead Sponsor

Trials

41

Recruited

3,600+

AdventHealth Translational Research Institute

Lead Sponsor

Trials

51

Recruited

5,900+

Findings from Research

GLP-1-based therapies for type 2 diabetes, including GLP-1 receptor agonists and DPP-4 inhibitors, effectively lower HbA1c levels by approximately 0.8-1.1% over 12 weeks, demonstrating their efficacy as both monotherapy and in combination with other diabetes medications.

These therapies not only improve glycemic control but also have a low risk of adverse events, including hypoglycemia, making them a safe treatment option, particularly beneficial when combined with metformin for patients not adequately controlled by metformin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 for type 2 diabetes. Ahrén, B.[2015]

GLP-1 is a hormone that helps regulate blood sugar levels by enhancing insulin secretion and inhibiting glucagon, making it a promising treatment for Type 2 diabetes without causing hypoglycemia.

Despite its rapid metabolism and the need for injection, advancements in delivery methods are making GLP-1-based therapies a viable alternative for managing diabetes and potentially obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Type 2 diabetes mellitus based on glucagon-like peptide-1. Holst, JJ.[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]

Glucagon and glucagon-like peptides (GLPs) play crucial roles in regulating blood glucose levels, with glucagon increasing glucose production in the liver and GLP-1 enhancing insulin secretion while inhibiting glucagon release, making them important for glucose homeostasis.

A pilot study on GLP-2 showed promising results in improving energy absorption and bone density in patients with short bowel syndrome, indicating potential therapeutic benefits for various diseases, including diabetes and intestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Glucagon-like peptides--synthesis, biological actions and some clinical implications]. Otto Buczkowska, E., Dworzecki, T.[2006]

References

1. United States pubmed.ncbi.nlm.nih.gov

GLP-1 for type 2 diabetes. [2015]

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

Treatment of Type 2 diabetes mellitus based on glucagon-like peptide-1. [2019]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1: Are its roles as endogenous hormone and therapeutic wizard congruent? [2022]

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

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

6. Poland pubmed.ncbi.nlm.nih.gov

[Glucagon-like peptides--synthesis, biological actions and some clinical implications]. [2006]

7. Denmark pubmed.ncbi.nlm.nih.gov

[A 45-fold liraglutide overdose did not cause hypoglycaemia]. [2017]

8. England pubmed.ncbi.nlm.nih.gov

The role of salt bridge formation in glucagon: an experimental and theoretical study of glucagon analogs and peptide fragments of glucagon. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

New Injectable Agents for the Treatment of Type 2 Diabetes Part 2-Glucagon-Like Peptide-1 (GLP-1) Agonists. [2019]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Glucagon and glucagon-like peptide receptors as drug targets. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Novel approaches to anti-obesity drug discovery with gut hormones over the past 10 years. [2021]