Insulin Therapy for Gestational Diabetes

(GAP Trial)

Overseen By Zaira Peterson, RN, MSN

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Medical College of Wisconsin

Disqualifiers: Pre-gestational diabetes, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Duration of pregnancy until delivery

416 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal time to start insulin treatment for pregnant women with gestational diabetes, a type of diabetes that develops during pregnancy. Researchers are comparing two groups: one begins insulin when 20% of blood sugar readings are high, and the other starts when 40% are high. They believe that starting earlier might reduce pregnancy complications. This trial suits pregnant women diagnosed with gestational diabetes who are not yet on any medication for it. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, and it seeks to understand how it benefits more patients.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, if you have already started medication for gestational diabetes before joining the study, you cannot participate.

What is the safety track record for these insulin treatments?

Research has shown that insulin is a trusted treatment for managing gestational diabetes (GDM) during pregnancy. Studies have found that insulin poses low risk for pregnant women and is the first-choice medication for treating GDM in the United States.

The FDA reviewed extensive information on insulin use during pregnancy and found it safe. Many pregnant women have used insulin successfully, and studies have not linked it to serious problems.

Overall, insulin reliably manages blood sugar levels in pregnant women with GDM. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard of care for gestational diabetes, which typically involves lifestyle changes and sometimes oral medications, this insulin therapy is unique because it tailors the initiation of insulin treatment to specific cutoff points of abnormal glucose values. Researchers are excited about this approach because it allows for more personalized treatment plans, potentially leading to better blood sugar control by intervening precisely when needed. Additionally, by allowing physicians to adjust dosages based on individual patient needs, this method offers flexibility, which could improve outcomes and overall patient satisfaction.

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

This trial will compare two approaches to starting insulin therapy for managing gestational diabetes. Research has shown that insulin effectively manages gestational diabetes. Studies indicate that women using insulin face a lower risk of complications such as early birth, small babies, and very large babies. Insulin use is also associated with better maternal health, with fewer instances of low blood sugar compared to other treatments. Overall, insulin helps maintain healthy blood sugar levels, benefiting both mother and baby. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for pregnant women over 18 with gestational diabetes who can communicate in English and check their blood sugar at least twice a day. It's not for those with pre-gestational diabetes, fasting blood sugar >=126 mg/dL, post-meal levels >=200 mg/dL, or already on pharmacotherapy.

Inclusion Criteria

You have been diagnosed with gestational diabetes.

Able to communicate in English

You are pregnant with only one baby.

Exclusion Criteria

You have already started taking medication before being referred to the study.

You have diabetes before getting pregnant.

You do not regularly check your blood sugar levels at least two times a day, even after getting proper advice.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Pregnant women with GDM are randomized to start pharmacotherapy at either 20% or 40% of elevated CBG values

Duration of pregnancy until delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neonatal outcomes

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview The GAP study is testing when to start insulin treatment for gestational diabetes by comparing two groups: one starts treatment if at least 20% of their blood glucose readings are high, the other waits until at least 40% are high.

How Is the Trial Designed?

Group I: 20% cutoff group Active Control 1 Intervention

Treatment intervention will be initiated with insulin if 20% cutoff of abnormal values is reached. Medication dosages will depend on the physician's discretion.

Group II: 40% cutoff group Active Control 1 Intervention

Treatment intervention will be initiated with insulin if 40% cutoff of abnormal values is reached. Medication dosages will depend on the physician's discretion.

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

Approved in European Union as Insulin for:

• Diabetes mellitus

Approved in United States as Insulin for:

• Diabetes mellitus

Approved in Canada as Insulin for:

• Diabetes mellitus

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborator

Trials

2,103

Recruited

2,760,000+

Published Research Related to This Trial

A 32-year-old obese woman with gestational diabetes experienced allergic reactions to Humulin U insulin, leading to its discontinuation after 17 days, but her glycemic levels were well-controlled with Humalog insulin thereafter.

Switching to Humalog, an ultra-short insulin, allowed for effective glycemic control throughout the remainder of her pregnancy, suggesting that this approach may be beneficial for managing gestational diabetes, especially when long-acting insulin needs to be stopped.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Insulin Lispro as an alternative for insulin Humulin U in the treatment of an obese gestational diabetic woman with allergy to Humulin U. Case report]. Sokup, A., Swiatkowski, M., Tyloch, M., et al.[2011]

Insulin pump therapy is safe and effective for women with gestational diabetes mellitus (GDM) or type 2 diabetes during pregnancy, showing improved glycemic control in 79% of users within 1-4 weeks.

Women using insulin pumps required higher insulin doses and experienced greater weight gain, but their babies did not show significant differences in weight or hypoglycemia compared to those not using pumps.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of insulin pumps in pregnancies complicated by type 2 diabetes and gestational diabetes in a multiethnic community. Simmons, D., Thompson, CF., Conroy, C., et al.[2021]

Insulin analogs like aspart and lispro are safe for use during pregnancy, showing no adverse effects on mothers or fetuses, while improving blood sugar control and reducing hypoglycemic episodes.

Insulin glargine is not recommended during pregnancy, but studies indicate it has a similar risk of congenital malformations as human insulin, based on data from 335 pregnancies with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin analogs and pregnancy: an update. Torlone, E., Di Cianni, G., Mannino, D., et al.[2015]

A review is being conducted on the safety and efficacy of basal insulin analogues, specifically insulin detemir, in pregnant women with type 1 diabetes, involving 470 participants across multiple centers.

The ongoing trial aims to compare insulin detemir with neutral protamine hagedorn insulin, focusing on maternal hypoglycemia, fetal outcomes, and key metrics like HbA1c and maternal weight gain, with results expected soon.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basal insulin analogues in diabetic pregnancy: a literature review and baseline results of a randomised, controlled trial in type 1 diabetes. Mathiesen, ER., Damm, P., Jovanovic, L., et al.[2022]

Insulin analogs, such as lispro, aspart, glargine, and detemir, are safer and more effective for managing diabetes during pregnancy compared to traditional insulins, as they do not cross the placenta and have favorable pharmacokinetic profiles that reduce blood glucose variability.

Metformin is also considered safe for use in pregnancy and may be an effective first-line treatment for milder cases of gestational diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The care of pregestational and gestational diabetes and drug metabolism considerations. Hedrington, MS., Davis, SN.[2017]

In a study of 437 women with gestational diabetes mellitus (GDM), it was found that Hispanic women and those without insurance were less likely to receive insulin as the first-line treatment, suggesting potential health disparities in treatment access.

Management of GDM by endocrinologists significantly increased the likelihood of insulin prescription compared to care by obstetricians, indicating that the type of healthcare provider may influence treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlates of Insulin Selection as a First-Line Pharmacological Treatment for Gestational Diabetes. Palatnik, A., Harrison, RK., Thakkar, MY., et al.[2023]

A 28-year-old woman with gestational diabetes required high doses of insulin (128 U/day) for treatment, but experienced allergic reactions at the injection site, leading to the discontinuation of insulin.

After stopping insulin, the patient achieved good metabolic control through diet modification and exercise, suggesting that nonpharmacologic treatments can be effective, especially in cases with high insulin resistance and a family history of type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Outcome of non-pharmacologic treatment in a gestational diabetic woman with high insulin resistance HOMA-IR index and allergy to human insulin. Case report]. Sokup, A., Swiatkowski, M., Tyloch, M., et al.[2017]

In a study of 113 women with type 1 diabetes, both long-acting insulin analogues, detemir and glargine, provided comparable glycaemic control throughout pregnancy, with similar HbA1c levels and rates of severe hypoglycaemia.

The study found that while pregnancy outcomes were generally similar, women using glargine had a lower prevalence of large for gestational age infants compared to those using detemir, suggesting a potential advantage of glargine in this aspect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes: comparison of glycaemic control and pregnancy outcome. Callesen, NF., Damm, J., Mathiesen, JM., et al.[2015]

In a review of 24 studies involving 3734 pregnant women with diabetes, insulin analogs aspart, glargine, and detemir were found to be safe, showing no increase in complications for mothers or fetuses.

Lispro was associated with higher birth weights and an increased incidence of large for gestational age (LGA) births compared to regular insulin, indicating a need for careful monitoring when using this treatment during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin analogs during pregnancy: a meta-analysis. Lv, S., Wang, J., Xu, Y.[2022]

Insulin detemir (IDet) is shown to be noninferior to insulin neutral protamine Hagedorn (NPH) for managing gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnant women, based on a study involving 87 participants.

The study found no significant differences in blood glucose control, maternal weight gain, or perinatal outcomes between the two insulin types, but the NPH group experienced more hypoglycemic events, suggesting IDet may be a safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Herrera, KM., Rosenn, BM., Foroutan, J., et al.[2016]

In a study of 25 women with gestational diabetes mellitus (GDM) who started metformin therapy, 64% achieved good blood sugar control, while 36% required insulin due to inadequate control or intolerance.

Fasting glucose levels during an oral glucose tolerance test were key predictors of metformin response; women with fasting glucose ≤5.2 mmol/L had a 93% chance of responding well to metformin, highlighting the importance of monitoring glucose levels in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting blood glucose predicts response to extended-release metformin in gestational diabetes mellitus. Corbould, A., Swinton, F., Radford, A., et al.[2014]

In a meta-analysis of 22 randomized controlled trials involving 9691 patients with type 2 diabetes, basal analog (BA) insulin regimens showed similar efficacy to premix (PM) insulin regimens in reducing HbA1c and postprandial glucose levels, but with a significant reduction in fasting glucose levels.

BA regimens were associated with lower rates of total hypoglycemia and less weight gain compared to PM regimens, indicating a better safety profile for BA insulin in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials. Hong, T., Lu, J., Zhang, P., et al.[2020]

In a 32-week study involving 686 patients with Type 2 diabetes, insulin detemir (IDet) therapy was found to be safe, with no serious adverse drug reactions reported and a significant reduction in total hypoglycemic events from 435 to 204.

Patients experienced improved glycemic control, as indicated by a decrease in glycated hemoglobin A1c from 9.9% to 7.7% and fasting plasma glucose from 11.9 mmol/L to 7.4 mmol/L, alongside a slight reduction in body weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical safety of insulin detemir in patients with Type 2 diabetes in the Gulf countries: The multicenter, noninterventional, open-label LevSafe study. El Shiekh, AR., Farrag, HA., Ashour, T., et al.[2020]

In a study comparing 25 women treated with insulin lispro (Humalog) and 46 treated with regular human insulin, pregnancy outcomes were similar, indicating that both treatments are effective for managing diabetes during pregnancy.

There were no significant differences in key outcomes such as HbA1c levels, pregnancy duration, neonatal birth weight, or rates of complications like preterm labor and cesarean sections, suggesting that Humalog is a safe alternative to regular insulin for pregnant women with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy complications and perinatal outcome in diabetic women treated with Humalog (insulin lispro) or regular human insulin during pregnancy. Cypryk, K., Sobczak, M., Pertyńska-Marczewska, M., et al.[2022]

In a non-inferiority trial involving 225 pregnant women with type 1 diabetes, insulin degludec was shown to be as effective as insulin detemir in controlling blood sugar levels, with similar HbA1c measurements before delivery.

Both insulins were found to have comparable safety profiles, indicating that degludec does not present additional safety concerns compared to detemir during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open‑label, multinational, randomised, controlled, non-inferiority trial. Mathiesen, ER., Alibegovic, AC., Corcoy, R., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3362948/

Meta-Analysis of Maternal and Neonatal Outcomes ... Overall, there was no difference in maternal age, body weight, or body mass index between the women using insulin glargine and those using NPH insulin, while ...

2. diabetesjournals.org diabetesjournals.org/care/article/48/Supplement_1/S306/157565/15-Management-of-Diabetes-in-Pregnancy-Standards

15. Management of Diabetes in Pregnancy: Standards of Care ... At around 16 weeks, insulin resistance begins to increase, and total daily insulin doses increase linearly by ∼5% per week through week 36. This ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402124002066

Gestational diabetes mellitus - Neonatal and maternal ... Women receiving insulin had a low risk of preterm, low birth weight, and macrosomia. •. Neonatal hypoglycemia was more common in the insulin-treated group.

4. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/s13098-022-00925-7

Maternal and neonatal outcomes with the use of long acting ... Findings suggest no significant differences in the maternal, perinatal and neonatal outcomes between intermediate and long-acting insulin analogues.

5. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2828808

Oral Glucose-Lowering Agents vs Insulin for Gestational ... Maternal hypoglycemia was reported in 20.9% with oral glucose-lowering agents and 10.9% with insulin (absolute risk difference, 10.0%; 95% CI, ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK545196/

Gestational Diabetes - StatPearls - NCBI Bookshelf This course explores the complexities of GDM, covering its risk factors, diagnostic criteria, and evolving approaches to management. Emphasis is ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4865394/

Insulin Use in Pregnancy: An Update - PMC - PubMed Central For these insulins, the FDA has received sufficient human data allowing these to be considered low risk in pregnancy.

8. diabetesjournals.org diabetesjournals.org/books/book/46/chapter/5050284/Medications-for-Diabetes-in-Pregnancy

Chapter 4: Medications for Diabetes in Pregnancy Insulin is the first-line medication for management of preexisting diabetes and GDM during pregnancy. Premixed insulins are usually avoided in pregnancy.

9. pharmacytech.therapeuticresearch.com pharmacytech.therapeuticresearch.com/api/sitecore/FileGuard/GetFile?id=e6563cb7-3d0a-4e7f-9501-1d607255c6e5

Chart-Comparison of Insulins (United States) This chart compares insulins in regard to onset, duration, and cost. It also provides information on route of administration, stability of in-use products ...