Insulin Therapy for Gestational Diabetes

(START2 Trial)

Recruiting at 1 trial location

Overseen By Rodney McLaren Jr, MD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Thomas Jefferson University

Must not be taking: Insulin, Corticosteroids

Disqualifiers: Pre-existing diabetes, Multi-fetal gestation, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: From initiation of insulin to delivery

430 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests insulin treatments for gestational diabetes, a type of diabetes that develops during pregnancy. Researchers aim to determine how different blood sugar level targets affect both the baby and the mother. Participants will join one of two groups: one with stricter blood sugar targets and another with more relaxed targets. The trial seeks pregnant women diagnosed with gestational diabetes after 24 weeks who do not have any other serious conditions. As an unphased trial, this study offers an opportunity to contribute to important research that could improve care for future mothers and babies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your healthcare provider.

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

Research has shown that insulin is generally safe to use during pregnancy, including for gestational diabetes (GDM). It is the preferred medication for managing diabetes in pregnant women due to its long history of use and well-understood effects.

Studies indicate that when used correctly, insulin usually does not harm the mother or baby. It helps control blood sugar levels, which is crucial for the health of both mother and baby. Different types of insulin may work faster or last longer, but all are generally well-tolerated.

While insulin is safe, it can have side effects like any medication. Some people might experience low blood sugar (hypoglycemia), which can cause shakiness or dizziness. However, with proper monitoring and adjustments, insulin therapy can be managed effectively.

In summary, insulin has a strong safety record when used during pregnancy, making it a reliable option for treating gestational diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores two different insulin therapy approaches for managing gestational diabetes. Unlike the standard treatment, which often involves a single target blood sugar range, this trial investigates both a strict target range of 65-120 mg/dL and a more permissive range of 65-140 mg/dL. The goal is to understand which approach better maintains blood sugar levels within the desired range while possibly offering more flexibility and ease for patients. This could lead to more personalized care options for pregnant individuals managing gestational diabetes.

What evidence suggests that this trial's treatments could be effective for gestational diabetes?

Research has shown that insulin is vital for managing gestational diabetes (GDM). It controls blood sugar levels, crucial for the health of both mother and baby. Studies have found that insulin use during pregnancy leads to better health outcomes for both newborns and mothers. Specifically, several large studies have linked insulin use to improved health around the time of birth. Insulin lowers blood sugar, helping prevent issues caused by high blood sugar during pregnancy. However, careful monitoring is essential, as insulin can increase the risk of low blood sugar in newborns. In this trial, participants will be assigned to either a strict or permissive insulin therapy arm, each with specific blood sugar target ranges, to evaluate the effectiveness and safety of different management strategies. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals diagnosed with gestational diabetes. Participants should be those who are being considered for pharmacotherapy to manage their blood sugar levels. Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and not have conditions that could interfere with the study.

Inclusion Criteria

Live, non-anomalous fetus

Literacy in English, Spanish, Mandarin, or Arabic

Patients are also required to provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.

Exclusion Criteria

I will be younger than 18 years old at my expected due date.

I cannot undergo an oral glucose tolerance test due to health reasons.

Pre-existing diabetes or diagnosis of GDM prior to 24 weeks

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are assigned to either a strict or permissive threshold for pharmacotherapy initiation and titration for gestational diabetes, monitored using continuous glucose monitoring

From initiation of insulin to delivery

Follow-up

Participants are monitored for maternal and neonatal outcomes, including neonatal composite outcomes and maternal hypoglycemia

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview The START 2 trial is testing two different blood sugar level targets for managing gestational diabetes with insulin therapy. One group will follow a 'Strict' target range of 65-120 mg/dL, while the other group will have a 'Permissive' range of 65-140 mg/dL. Both aim for a time in range goal of 70%.

How Is the Trial Designed?

Group I: Strict Arm Active Control 1 Intervention

The Strict study arm target range will be 65-120 mg/dL, with time in range goal of 70%.

Group II: Permissive Active Control 1 Intervention

The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

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?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. 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 ...

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

Insulin Use in Pregnancy: An Update - PMC - PubMed Central Outcomes were similar to those of regular insulin (24,25). ... Regular insulin, insulin aspart, insulin lispro, and NPH have the most human pregnancy data.

3. 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.

4. 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 ... Treatment of GDM with lifestyle and insulin has been demonstrated to improve perinatal outcomes in two large RCTs, as summarized in a U.S. ...

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

Gestational diabetes mellitus - Neonatal and maternal ... The insulin-treated group exhibited a 4.43 times higher risk of neonatal hypoglycemia than the diet group. Insulin-treated individuals, stratified by PS, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6464609/

Different insulin types and regimens for pregnant women with ... Long‐term outcomes of offspring born to diabetic mothers include an increased risk of obesity, impaired cognitive ability, and type 2 diabetes. Management of DM ...

7. iehp.org iehp.org/content/dam/iehp-org/en/documents/members/helpful-information-and-resources/medical_services_comparison-of-insulins_2019.pdf

Comparison of Insulins (Information specific to U.S. products). This chart compares insulins in regard to duration, usual frequency, and cost. It also provides information on ...

8. medicaid.nv.gov medicaid.nv.gov/Downloads/provider/Insulins_2017-03.pdf

Therapeutic Class Overview - Insulins *HUMULIN R U-500 is useful for the treatment of insulin-resistant patients with diabetes requiring daily doses of more than 200 units. HUMULIN R U-. 100 may ...