Glucagon for Obesity

(GIO B Trial)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

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

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of this study is to examine the effect of prolonged (72 hour) administration of glucagon compared to placebo on energy expenditure in healthy, non-diabetic, obese subjects.

Will I have to stop taking my current medications?

The trial requires that you stop taking any medication known to significantly impact body weight or energy metabolism within 3 months prior to screening, except for stable hormone replacement therapy. Additionally, you must stop taking selective serotonin reuptake inhibitors or medications for depression one week prior to screening.

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 food intake. This suggests that treatments involving glucagon or its analogues might also be effective for weight management. ^{1 2 3 4 5}

Is glucagon safe for human use?

Glucagon is a hormone that helps regulate blood sugar levels and is generally considered safe for human use. It has been studied for its role in managing glucose levels in both animals and humans, and no major safety concerns have been reported in the available research. ^{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 5 10 11}

Research Team

Steven Smith, MD

Principal Investigator

Study Principal Investigator

Eligibility Criteria

This trial is for healthy, non-diabetic obese adults aged 18-55 with a BMI of 27 to 45 kg/m2 and stable weight. Participants must not have significant health issues, take certain medications affecting weight or energy metabolism, or have had bariatric surgery. They should not be pregnant, breastfeeding, or unwilling to use birth control if applicable.

Inclusion Criteria

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

I can avoid drinking alcohol for 2 days before my study visit.

Willing to avoid strenuous physical activity for 72 hours prior to the inpatient study visit

Exclusion Criteria

I haven't taken weight or metabolism affecting drugs in the last 3 months, except for stable hormone therapy.

Blood donation within 4 weeks prior to screening

You have used illegal drugs or nicotine products in the past three months before screening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a continuous IV infusion of glucagon or placebo for 72 hours

72 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Glucagon
• Placebo

Trial Overview The study tests the effects of glucagon versus placebo on energy expenditure over a period of 72 hours in obese individuals. It aims to understand how prolonged glucagon administration can influence calorie burning in the body without any dietary changes.

Participant Groups

Group I: Glucagon High Dose Active Control 1 Intervention

Group II: Glucagon Low Dose Active Control 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

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 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]

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-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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

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

GLP-1 for type 2 diabetes. [2015]

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

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

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]