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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how the body tolerates glucagon, a hormone that can affect weight. Participants will receive glucagon through an infusion to determine if it causes any side effects, such as nausea. The trial seeks individuals who have been obese (BMI between 27 and 40) but do not have diabetes or other serious health issues. Participants must not have used any medications that affect weight and should have maintained a stable weight for the past three months.

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 new treatment.

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.

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

Research has shown that glucagon has been studied for various uses, with some results providing insights into its safety. A study that combined results from several trials found that glucagon significantly lowered the risk of hypoglycemia (low blood sugar), indicating good safety. This suggests glucagon is generally well-tolerated in certain situations.

However, this trial is in the early stages of testing glucagon for obesity. Early trials primarily focus on safety, so researchers are closely observing how participants respond to the treatment. In this study, glucagon is administered at different rates to assess how well participants tolerate these doses.

Prospective participants should understand that safety details are still being determined, and experiences may vary. Participants will be closely monitored for any side effects, such as nausea, which is specifically being checked during the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for obesity, which often focus on lifestyle changes or appetite suppression, Glucagon infusion works by elevating energy expenditure and promoting fat breakdown. Researchers are excited about this approach because it targets a different metabolic pathway, offering a novel method to manage obesity. Additionally, the precise and escalating infusion of Glucagon allows for careful control of dosage, potentially minimizing side effects like nausea and improving patient tolerance. This unique mechanism could provide an alternative for individuals who have not found success with existing therapies.

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

Studies have shown that certain medications, called GLP-1 receptor agonists, can aid in weight loss. These medications mimic natural hormones in the gut that regulate hunger and energy use. Research indicates that these drugs effectively manage blood sugar levels and assist with weight loss. In one study, a treatment related to glucagon resulted in an average weight loss of up to 14.7% in adults with obesity over 36 weeks. Although direct evidence on using glucagon alone for weight loss is limited, its role in controlling metabolism and reducing weight appears promising. This trial will specifically investigate the effects of glucagon infusion on weight loss, suggesting its potential benefits. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven R Smith, MD

Principal Investigator

Prinicipal Investigator

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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, 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]

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/PMC10980663/

Real-World Effectiveness of Once-Weekly Glucagon-Like ... The study reinforces that OW GLP-1RAs are more effective in glycemic control and weight reduction compared with DPP-4is in people with T2DM in the real-world ...

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. 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 ... Low-dose glucagon reduces exercise-induced hypoglycemia and TBR in T1D individuals. Future research should optimize glucagon dosage and timing ...

6. 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% ...

7. ahajournals.org ahajournals.org/doi/10.1161/JAHA.122.029282

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. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/abs/10.1111/dom.14640

Efficacy and safety of high‐dose glucagon‐like peptide‐1 ... A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high-dose GLP-1 RAs or tirzepatide, respectively. The glucose- ...

9. nature.com nature.com/articles/s41366-024-01473-y

What is the pipeline for future medications for obesity? In this review, we present the efficacy and safety data for the pipeline of obesity pharmacotherapies with a focus on entero-pancreatic hormone-based ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S2212877825000365

A once-daily GLP-1/GIP/glucagon receptor tri-agonist ... NN1706 lowers body weight & improves glycemic control in obese rodents and monkeys. NN1706 treatment led to 8.2% weight loss from baseline after 10 weeks.