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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how certain genetic differences affect insulin release and blood sugar control. It tests a treatment called Exendin-9,39, which may help manage high blood sugar by targeting a specific gene involved in insulin production. Participants will receive either Exendin-9,39 or a placebo (a harmless substitute) to compare effects. The trial seeks non-diabetic individuals who know their genetic makeup related to the GLP1R gene. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for blood sugar management.

Will I have to stop taking my current medications?

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

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

Research has shown that Exendin-9,39 has been tested for safety and tolerability. Some studies suggest it can help control blood sugar by influencing insulin release. Importantly, Exendin-9,39 is usually well-tolerated.

While using Exendin-9,39, some people have experienced mild side effects, such as nausea. In rare cases, allergic reactions like skin rashes or trouble breathing may occur. These reactions are uncommon but important to be aware of.

Research on similar treatments, such as exenatide used for diabetes, has shown they are safe over long periods. This provides some confidence in the safety of Exendin-9,39. However, always discuss any potential risks with the study team before joining. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for high blood sugar focus on regulating insulin or enhancing the body's response to it. However, Exendin-9,39 works differently by blocking the action of certain hormones in the gut that affect blood sugar levels. This innovative approach could offer a new way to manage blood sugar without directly altering insulin levels. Researchers are excited because this could lead to more options for controlling blood sugar with potentially fewer side effects related to insulin management.

What evidence suggests that Exendin-9,39 might be an effective treatment for high blood sugar?

Research has shown that Exendin-9,39, one of the treatments in this trial, can help manage blood sugar by influencing insulin release. In a study with mice, Exendin-9,39 corrected low blood sugar by reducing insulin production, indicating it might help control blood sugar levels. Additionally, studies on exenatide, a related substance, have shown it effectively lowers blood sugar in people with type 2 diabetes. This suggests that Exendin-9,39, which participants in this trial may receive, could also effectively manage high blood sugar in humans. ^{1 2 3 5 6}

Who Is on the Research Team?

Adrian Vella, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03373435

NCT03373435 | Safety and Efficacy of Exendin 9-39 in ... This clinical study will evaluate whether taking an investigational drug called exendin 9-39 is safe, well-tolerated, and helps to prevent low blood sugar in ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3447900/

GLP-1 Receptor Antagonist Exendin-(9-39) Elevates ... We showed that the GLP-1 receptor antagonist exendin-(9-39) suppresses insulin secretion and corrects fasting hypoglycemia in SUR-1 −/− mice.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0025619615000518

Five-Year Efficacy and Safety Data of Exenatide Once ... Significant improvements in fasting plasma glucose level (–28.8 mg/dL; 95% CI, −36.2 to −21.5 mg/dL), weight (–3.0 kg; 95% CI, –4.6 to –1.3 kg), lipids, and ...

4. withpower.com withpower.com/trial/exendin-939-for-high-blood-sugar-in-healthy-subjects-83daa

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 ...

5. diabetesjournals.org diabetesjournals.org/care/article/27/11/2628/23838/Effects-of-Exenatide-Exendin-4-on-Glycemic-Control

Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 ... CONCLUSIONS—Exenatide significantly reduced HbA1c in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally ...

6. mayoclinicproceedings.org mayoclinicproceedings.org/article/S0025-6196(15)00051-8/abstract

Five-Year Efficacy and Safety Data of Exenatide Once ... Long-term safety data included adverse events, liver and renal function, and heart rate. Results. Of 258 extension-phase patients, 153 (59.3%) completed 5 years ...