Glucagon for Obesity

(GIO B 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, Antidepressants, Apomorphine

Disqualifiers: Diabetes, Cardiovascular disease, Liver disease, Renal disease, Sleep apnea, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 72 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how glucagon, a hormone, affects energy use in healthy, non-diabetic, obese individuals. Participants are divided into groups receiving either a high dose, a low dose of glucagon, or a placebo (a substance with no active treatment). The goal is to determine if glucagon can aid in weight management by increasing energy expenditure. The trial seeks participants who have been obese with a stable weight for at least three months and do not have diabetes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that glucagon has been safely used in other medical situations. For instance, a review of studies on low-dose glucagon for people with Type 1 diabetes found it helped manage low blood sugar without major side effects. This suggests that glucagon is generally safe at low doses.

This trial tests both high and low doses of glucagon for weight loss. As an early-stage trial, the main goal is to determine the safety of these doses for participants. While specific safety data for glucagon in weight loss is not yet available, its safe use in other conditions offers some reassurance. The trial aims to confirm that glucagon is safe and well-tolerated for this new application. Participants should discuss any potential risks and benefits with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for obesity, which often focus on appetite suppression or calorie absorption reduction, glucagon offers a novel approach by potentially increasing energy expenditure. Researchers are excited about glucagon because it targets the body's metabolism, encouraging it to burn more calories. This treatment could provide a new avenue for weight management by stimulating metabolic processes rather than just limiting intake. Furthermore, the study is exploring different doses of glucagon, which might help tailor treatment to individual needs, offering a more personalized approach to managing obesity.

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

Research has shown that glucagon, a hormone naturally produced by the body, can increase energy expenditure by raising blood sugar levels. This trial will test different doses of glucagon to evaluate its potential in weight management. Studies have found that treatments similar to glucagon can help control body weight by influencing energy use and appetite. While glucagon is primarily known for managing blood sugar, it might also aid in weight management by boosting metabolism and reducing appetite. These effects make glucagon a promising option for treating obesity. ^{1 2 6 7 8}

Who Is on the Research Team?

Steven Smith, MD

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

Citations

1. 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 in ...

2. nature.com nature.com/articles/d41573-025-00155-2

The evolution of the obesity drug market These agents mimic gut hormones that regulate appetite and energy metabolism, offering more targeted effects and improved cardiovascular and ...

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

Low-Dose Glucagon to Prevent and Treat Exercise ... An injectable dose of 100–300 μg of glucagon is effective by increasing blood glucose levels by ∼1.5–2 mmol/L within 15 min (12). It has also ...

4. delveinsight.com delveinsight.com/blog/novo-vs-eli-lilly-in-anti-obesity-drug-market

Novo Nordisk vs Eli Lilly: Who's Winning the Obesity Drug ... In June 2023, Lilly reported that Orforglipron led to an average weight loss of up to 14.7% over 36 weeks in adults with obesity or overweight ...

5. science.org science.org/doi/10.1126/science.adq6452

Winning researchers unlocked GLP-1 drugs for obesity In 2014, it was approved as Saxenda for weight loss, averaging a reduction of about 8% of overall body mass—slightly more than what other drugs ...

6. diabetesjournals.org diabetesjournals.org/care/article/48/9/1637/163215/Low-Dose-Glucagon-to-Prevent-and-Treat-Exercise

Low-Dose Glucagon to Prevent and Treat Exercise ... This systematic review aims to determine whether using low-dose glucagon in individuals with T1D reduces the risk of hypoglycemic events and/or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10381974/

Role of Glucagon‐Like Peptide‐1 Receptor Agonists in ... Obesity‐related benefits resulting from GLP‐1 RA actions in the brain include reduction in body weight, appetite, food cravings, and energy ...

8. biopharmadive.com biopharmadive.com/news/lilly-third-quarter-2025-earnings-zepbound-mounjaro-obesity-sales/804232/

Lilly hikes revenue forecasts on booming obesity drug sales Meanwhile, Novo is in a battle to acquire the obesity drug developer Metsera, offering as much as $9 billion to counter a competing bid from ...