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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how exenatide, a drug typically used for type II diabetes, might help control blood sugar in pregnant women with gestational diabetes. Researchers aim to understand how the body processes the drug and its effectiveness in aiding the pancreas to produce insulin after meals. This is crucial because current treatments, like insulin injections and glyburide pills, may not work well and can cause side effects. Pregnant women with one baby who have gestational diabetes and are not on medication might be suitable for this study. As a Phase 4 trial, this research seeks to understand how an already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for exenatide?

Research shows that exenatide is generally safe and effective for lowering blood sugar in people with type II diabetes who are not pregnant. Clinical trials have found it works well alone or with other diabetes medications. However, exenatide is not yet approved for use during pregnancy.

Some animal studies have shown possible risks. For example, in mice, using exenatide during pregnancy led to more deaths in newborns at high doses, which were much higher than those used in humans.

Researchers are currently studying exenatide in pregnant women to determine if it can safely help control blood sugar. The trial's later stage suggests some existing evidence of safety, but more research is needed to confirm its safety specifically for gestational diabetes. Participants in this trial will provide valuable information on how exenatide affects pregnant women. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Exenatide for gestational diabetes because it offers a unique approach compared to standard treatments like insulin or metformin. Unlike these options, Exenatide is a GLP-1 receptor agonist, which enhances insulin secretion in response to meals and can also promote weight loss. This dual action not only helps manage blood sugar levels but may also address weight concerns, which is beneficial for pregnant individuals. Additionally, Exenatide is administered via a subcutaneous injection, providing a different delivery method that could offer more consistent glucose control.

What is the effectiveness track record for exenatide in treating gestational diabetes?

Research has shown that exenatide, a medication used to lower blood sugar, works well for non-pregnant people with type II diabetes. Studies have found that exenatide helps lower HbA1c levels, a measure of long-term blood sugar control. It also promotes weight loss and reduces the risk of low blood sugar episodes. Exenatide enhances the pancreas's ability to release insulin, stabilizing blood sugar levels after meals. In this trial, participants will receive exenatide to evaluate its potential benefits for gestational diabetes, building on its success in other types of diabetes. ^{1 6 7 8 9}

Who Is on the Research Team?

Maisa Feghali, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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 (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]

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]

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® (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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02974244

Study Details | NCT02974244 | Comparison of the ... Outcomes and Analysis: To measure the effectiveness of Bydureon relative to basal insulin are changes in HbA1c and body weight, as well as changes in HbA1c ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12499737/

New developments in GLP-1 agonist therapy for ... Some GLP-1, such as liraglutide and exenatide, have shown potential outcomes in non-pregnant populations for improving blood glucose levels and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5688980/

Tolerability and Effectiveness of Exenatide Once Weekly ... Treatment with EQW, relative to BI, was associated with larger reductions in HbA1c and weight and reduced risk of hypoglycemia.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03970044

Effectiveness of Exenatide Plus Dapagliflozin on 24 Hour ... This is a Phase IV, single site, randomized, open-label, parallel study comparing BYDUREON-BCise plus FARXIGA to BYDUREON-BCise alone and FARXIGA alone

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002937824008640

Glucagon-like peptide-1 receptor agonist use in pregnancy GLP-1RA use, presumably through its effect on weight loss, leads to improved fertility, providing an opportunity to evaluate maternal, fetal, and neonatal risks ...

6. drugs.com drugs.com/pregnancy/exenatide.html

Exenatide Use During Pregnancy In mice, exposure during gestation and lactation caused increased neonatal deaths at exposures 3 times the maximum recommended human dose. There ...

7. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK518981/

Exenatide - StatPearls - NCBI Bookshelf - NIH However, clinical trials have shown Exenatide to be both safe and effective when used as monotherapy or in combination with other diabetic ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05482789

Exenatide Pharmacokinetics and Pharmacodynamics in ... Women in the first trimester of pregnancy · Hematocrit less than 30% · Current or past treatment with any hypoglycemic agent · Women with gastrointestinal disease ...

9. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16437

Glucagon‐like peptide 1 (GLP‐1) receptor agonists' use ... Preterm birth rate was lower in the GLP1-RA cohort (8.0%) compared to cohorts with diabetes (15.1%) and obesity (14.5%). However, there were ...