Exendin-9,39 for High Blood Sugar in Healthy Subjects

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Adrian Vella

Disqualifiers: Diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The GLP-1 receptor (GLP1R) gene is found on the beta cells of the pancreas. Its role is in the control of blood sugar level by enhancing insulin secretion from the pancreas after eating a meal. The purpose of this research study to find out how genetic variations in GLP1R alter insulin secretion, in the fasting state and when blood sugars levels are elevated.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Exendin-9,39 for high blood sugar in healthy subjects?

Research on exenatide, a component of Exendin-9,39, shows it effectively lowers blood sugar levels and reduces body weight in people with type 2 diabetes. It is generally well-tolerated and offers the convenience of once-weekly dosing. ^{1 2 3 4 5}

Is Exendin-9,39 (Exenatide) safe for humans?

Exenatide, used for diabetes, is generally safe but can cause nausea and, in rare cases, allergic reactions like skin rashes and breathing difficulties. It does not typically cause low blood sugar or require frequent blood sugar checks. ^{1 2 5 6 7}

How is the drug Exendin-9,39 different from other treatments for high blood sugar?

Exendin-9,39 (also known as exenatide) is unique because it is a long-acting drug that can be administered once weekly, unlike other treatments that require more frequent dosing. It works by enhancing insulin secretion when blood sugar is high, suppressing excess glucagon (a hormone that raises blood sugar), and slowing down stomach emptying, which helps control blood sugar levels without causing low blood sugar episodes. ^{1 2 8 9 10}

Research Team

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for nondiabetic individuals aged 25-65. It's specifically looking at how genetic differences in a gene called GLP1R affect insulin secretion when fasting and during high blood sugar levels. Participants will be split into two groups based on their genetics: one with the AA genotype and another with the GG genotype at rs3765467.

Inclusion Criteria

I am between 25 and 65 years old.

My genetic test shows I have either the AA or GG genotype at rs3765467.

I am not diabetic.

Exclusion Criteria

I am either younger than 25 or older than 65.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Saline (Placebo) or Exendin-9,39 (Active Comparator) to evaluate the effect on beta-cell function during fasting and hyperglycemia

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exendin-9,39
• Saline

Trial Overview The study tests the effects of saline (a placebo) and Exendin-9,39 (which affects insulin secretion) on beta-cell function in healthy subjects. The goal is to understand how variations in the GLP1R gene influence this process under different blood sugar conditions.

Participant Groups

Group I: Exendin-9,39 Active Control 1 Intervention

Exendin-9,39 will be infused during the study

Group II: Saline Placebo Group 1 Intervention

Saline will be infused during the study

Exendin-9,39 is already approved in United States, European Union for the following indications:

Approved in United States as Exenatide for:

• Type 2 diabetes

Approved in European Union as Exenatide for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Adrian Vella

Lead Sponsor

Trials

9

Recruited

210+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

In a study of 150 patients with type 2 diabetes, adding once-weekly exenatide to basal insulin therapy resulted in a significant reduction in HbA1c levels by 0.7% after one year, comparable to the 0.8% reduction seen with once-daily liraglutide.

Patients on exenatide were more likely to achieve an HbA1c of less than 7% compared to those on liraglutide, with no increase in hypoglycemia incidents, indicating that exenatide is a safe and effective addition to insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A real-world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672). Stryker, MD., Kane, MP., Busch, RS.[2023]

Bydureon, a long-acting formulation of exenatide, allows for once-weekly injections, significantly reducing glycated hemoglobin (HbA1c) levels while maintaining similar weight loss and better digestive tolerance compared to the original twice-daily formulation.

In clinical comparisons, Bydureon has shown greater efficacy than other glucose-lowering medications like sitagliptin and pioglitazone, without causing hypoglycemia, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)]. Scheen, AJ.[2022]

In a study of 30,097 patients with type 2 diabetes, adherence to therapy was significantly higher for exenatide once weekly (88%) compared to liraglutide once daily (77%) over a 6-month period.

Patients taking exenatide had 1.78 times higher odds of maintaining good adherence (PDC ≥ 0.80) compared to those on liraglutide, suggesting that the once-weekly dosing may improve treatment compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in Germany. Qiao, Q., Ouwens, MJ., Grandy, S., et al.[2020]

Exenatide extended-release (ER) significantly improves blood sugar control and reduces body weight in patients with type 2 diabetes over 24-30 weeks, with effects maintained for up to 6 years.

It is generally well tolerated with a low risk of hypoglycemia, though common side effects include mild gastrointestinal issues and headaches, making it a convenient once-weekly treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. Syed, YY., McCormack, PL.[2018]

In a study of 179 Japanese patients with type 2 diabetes who were not adequately controlled on oral medications, exenatide significantly improved glycemic control, with HbA1c reductions of -1.34% for 5 μg and -1.62% for 10 μg compared to placebo (-0.28%).

Exenatide at 10 μg also led to a significant reduction in body weight (-1.54 kg) compared to placebo, although it was associated with a higher incidence of mild to moderate nausea and hypoglycemia, particularly at the higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks. Kadowaki, T., Namba, M., Imaoka, T., et al.[2022]

Exenatide is an effective treatment for type 2 diabetes that helps lower blood sugar levels and HbA1c without causing hypoglycemia or requiring regular blood glucose monitoring, making it a convenient option for patients.

It not only stimulates insulin secretion and inhibits glucagon but also promotes weight loss and slows gastric emptying, which can be particularly beneficial for overweight or obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. Scheen, AJ., Van Gaal, LF.[2018]

A 52-year-old male experienced systemic hypersensitivity reactions to the GLP-1 receptor agonist exenatide after multiple injections, indicating a potential safety risk associated with this medication class.

Positive skin tests confirmed the hypersensitivity to exenatide, while liraglutide was tolerated without issues, highlighting the need for careful monitoring of patients using GLP-1 receptor agonists for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. Steveling, EH., Winzeler, B., Bircher, AJ.[2021]

Exenatide is an effective treatment for type 2 diabetes, but its short plasma half-life of 2.4 hours limits its use, leading to the development of products like Byetta™ and Bydureon™.

Recent research has focused on creating long-acting formulations of exenatide through various methods, including sustained-release dosage forms and structural modifications, to enhance its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting preparations of exenatide. Cai, Y., Wei, L., Ma, L., et al.[2021]

In a study of 109 patients with type 2 diabetes, subcutaneous injections of AC2993 significantly reduced HbA(1c) levels by 0.7 to 1.1% compared to placebo, indicating improved blood sugar control.

AC2993 also enhanced beta-cell function, with a 50-100% increase in the beta-cell index, while the most common side effect reported was mild-to-moderate nausea, suggesting it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Fineman, MS., Bicsak, TA., Shen, LZ., et al.[2022]

Subcutaneous injection of exendin 9-39 (Ex-9) significantly prevented hyperinsulinaemic hypoglycaemia in patients with post-bariatric hypoglycaemia, improving glucose levels and reducing insulin peaks and related symptoms.

The treatment was well tolerated with no adverse events reported, suggesting that Ex-9 is a safe and effective option for managing PBH, warranting further studies on its long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and pharmacokinetics of subcutaneous exendin (9-39) in patients with post-bariatric hypoglycaemia. Craig, CM., Liu, LF., Nguyen, T., et al.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

A real-world, observational study of weekly exenatide added to basal insulin in patients with type 2 diabetes mellitus (NCT02895672). [2023]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)]. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Adherence to GLP-1 receptor agonist therapy administered by once-daily or once-weekly injection in patients with type 2 diabetes in Germany. [2020]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

Improved glycemic control and reduced bodyweight with exenatide: A double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks. [2022]

6. Belgium pubmed.ncbi.nlm.nih.gov

[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. [2018]

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

Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Long-acting preparations of exenatide. [2021]

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

Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Efficacy and pharmacokinetics of subcutaneous exendin (9-39) in patients with post-bariatric hypoglycaemia. [2018]