Exenatide for Gestational Diabetes

Overseen By Maisa Feghali, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Maisa N. Feghali, MD

Must not be taking: Hypoglycemic agents

Disqualifiers: First trimester, Gastrointestinal disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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: 2

Duration: 1 week

13 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who have been treated with any hypoglycemic agents (medications that lower blood sugar).

What data supports the effectiveness of the drug exenatide for gestational diabetes?

Exenatide, used for type 2 diabetes, has been shown to improve blood sugar control and help with weight loss, which might be beneficial for managing gestational diabetes. It works by enhancing insulin secretion and reducing appetite, with studies showing it effectively lowers blood sugar levels and body weight in type 2 diabetes patients. ^{1 2 3 4 5}

Is exenatide safe for use in humans?

Exenatide has been associated with some safety concerns, including nausea, systemic allergic reactions, and in rare cases, acute pancreatitis (inflammation of the pancreas). While it is generally used for diabetes management, these potential side effects should be considered. ^{1 2 6 7 8}

How is the drug exenatide unique for treating gestational diabetes?

Exenatide is unique because it is a once-weekly injection that slowly releases the medication over time, which can be more convenient compared to other treatments that require daily dosing. It is a GLP-1 receptor agonist, which means it helps the body release insulin in response to meals, potentially offering better blood sugar control without causing low blood sugar (hypoglycemia) like some other diabetes medications. ^{1 2 6 7 9}

What is the purpose of this trial?

This study is being done to study how exenatide, an FDA-approved drug that lowers blood sugar in non-pregnant patients with type II diabetes, works in pregnant women. To do this, the investigators will study the drug's pharmacokinetics (what the body does to the drug; specifically, how quickly your body breaks down and excretes exenatide) and pharmacodynamics (what the drug does to the body; specifically, how effectively exenatide helps the participants' pancreas secrete insulin and how well it controls blood sugar after a meal). There are only two main drug therapies (insulin injections and glyburide pills) currently used for gestational diabetes and not all women achieve good enough blood sugar control without side effects. Therefore, the investigators hope to find out if exenatide might also be helpful in gestational diabetes.

Research Team

Maisa Feghali, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

This trial is for pregnant women aged 18-50 with gestational diabetes that doesn't yet require medical therapy. Participants must be able to consent and not in their first trimester. Women with low blood counts, gastrointestinal issues, high triglycerides, gallbladder or pancreatic disease, past hypoglycemic treatments, or kidney problems cannot join.

Inclusion Criteria

Pregnant women (singleton)

Able to give written informed consent

You have gestational diabetes that does not need treatment with medication.

Exclusion Criteria

I have taken medication to lower my blood sugar.

I am a woman with stomach issues like nausea or pain that need treatment.

Your hematocrit level is lower than 30%.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive an injection of 10 micrograms of Exenatide sub-cutaneously, followed by a mixed meal test and blood sample collection for laboratory testing

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Exenatide

Trial Overview The study tests how exenatide affects blood sugar control in pregnant women with gestational diabetes by examining how the body processes the drug and its effectiveness at controlling blood sugar after meals.

Participant Groups

Group I: Exenatide Experimental Treatment 1 Intervention

Participant receives injection of 10 micrograms of Exenatide sub-cutaneously the given mixed meal test and blood samples will be drawn for laboratory testing.

Exenatide is already approved in United States, European Union for the following indications:

Approved in United States as Byetta for:

• Type 2 diabetes mellitus

Approved in United States as Bydureon for:

• Type 2 diabetes mellitus

Approved in United States as Bydureon BCise for:

• Type 2 diabetes mellitus

Approved in European Union as Byetta for:

• Type 2 diabetes mellitus

Approved in European Union as Bydureon for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Maisa N. Feghali, MD

Lead Sponsor

Trials

3

Recruited

130+

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]

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]

Exenatide, a GLP-1 receptor agonist, has been shown to effectively lower HbA1c levels by 0.8% to 1.9% in type 2 diabetes patients over various clinical trials, while also promoting weight loss of up to 8 kg, making it a beneficial treatment option.

The treatment is generally well-tolerated, with mild gastrointestinal side effects being the most common, and a low incidence of hypoglycemia, highlighting its safety profile compared to other diabetes therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of exenatide as a diabetes therapeutic. Bhavsar, S., Mudaliar, S., Cherrington, A.[2022]

Exenatide, a GLP-1 receptor agonist approved for type 2 diabetes, significantly reduces glycosylated hemoglobin (HbA1c) by about 1% and promotes weight loss of approximately 5.3 kg over 82 weeks, without causing hypoglycemia.

The treatment is generally safe, with a low risk of acute pancreatitis and manageable side effects like mild nausea, which led to a 6% dropout rate in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus. Gallwitz, B.[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]

Bydureon® (Bdn) is a long-acting injectable treatment for type 2 diabetes that releases exenatide slowly over two months, minimizing initial release to reduce side effects.

The study identified that peptide acylation is a significant degradation product during the release of exenatide, which may contribute to immunogenicity, highlighting the need for further investigation into the stability and safety of the formulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of attributes and in vitro performance of exenatide-loaded PLGA long-acting release microspheres. Li, T., Chandrashekar, A., Beig, A., et al.[2021]

Exenatide (Byetta) was prescribed to a female type 2 diabetic patient for glycemic control, but she experienced gastrointestinal disturbances from the first day of treatment.

After eight days of using Exenatide, the patient developed acute pancreatitis, which was confirmed by CT scan; the medication was discontinued, and her symptoms improved with treatment for pancreatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide and acute pancreatitis. Tripathy, NR., Basha, S., Jain, R., et al.[2018]

In a study of 188 patients with type 2 diabetes who were treated with insulin and exenatide for up to 27 months, exenatide significantly reduced HbA1c levels, indicating improved glycemic control, with a mean reduction of -0.66% in the first 6 months.

Patients also experienced significant weight loss over time, averaging -6.2 kg by 18 months, and a decrease in prandial insulin requirements, suggesting that exenatide can enhance insulin therapy effectiveness while promoting weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. Yoon, NM., Cavaghan, MK., Brunelle, RL., et al.[2022]

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

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

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Evolution of exenatide as a diabetes therapeutic. [2022]

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

Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus. [2022]

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

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

7. Netherlands pubmed.ncbi.nlm.nih.gov

Characterization of attributes and in vitro performance of exenatide-loaded PLGA long-acting release microspheres. [2021]

8. India pubmed.ncbi.nlm.nih.gov

Exenatide and acute pancreatitis. [2018]

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

Exenatide added to insulin therapy: a retrospective review of clinical practice over two years in an academic endocrinology outpatient setting. [2022]