Insulin Thresholds for Gestational Diabetes

(START 1 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: Throughout pregnancy until delivery

430 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for gestational diabetes (GDM). Our goal is to compare a strict and permissive threshold. The strict threshold is defined as two abnormal values or more over a one-week period (two fasting values elevated, two of the same post prandial values elevated, or 1 fasting and 1 post prandial value elevated), whereas the permissive threshold is defined as 50% of values elevated over 1 week (50% of overall fasting values, 50% of postprandial values, or 50% of overall values).

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 doctor.

Is insulin safe for use in humans, including during pregnancy?

Research shows that insulin, including various analogs like lispro, aspart, glargine, and detemir, is generally safe for humans, including during pregnancy. Studies indicate no significant differences in adverse events compared to regular human insulin, and these analogs do not cross the placenta, reducing risks for both mother and baby. ^{1 2 3 4 5}

How does insulin differ from other drugs for gestational diabetes?

Insulin is often used when diet and exercise alone do not control gestational diabetes, and it can be tailored in terms of dosage and timing to meet individual needs. Unlike oral medications like metformin, insulin can be adjusted more precisely to manage blood sugar levels, and newer formulations offer options for those with allergies or specific timing needs. ^{6 7 8 9 10}

What data supports the effectiveness of the drug Insulin for Gestational Diabetes?

Research shows that insulin, including types like Humalog, can effectively control blood sugar levels in pregnant women with gestational diabetes, ensuring good glycemic control until delivery. Additionally, insulin glargine has been studied for safety during pregnancy in women with type 1 diabetes, suggesting its potential use in gestational diabetes as well. ^{6 11 12 13 14}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals with gestational diabetes diagnosed after 24 weeks, carrying a single fetus without anomalies. Participants must be literate in English, Spanish, Mandarin, or Arabic and give informed consent. It excludes those under 18 at expected delivery date (EDD), with pre-existing diabetes or multiple fetuses.

Inclusion Criteria

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.

Live, non-anomalous fetus

Exclusion Criteria

Known allergy to insulin

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

I am under 18 years old.

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 initiation and titration of pharmacotherapy for gestational diabetes

Throughout pregnancy until delivery

Follow-up

Participants are monitored for maternal and neonatal outcomes, including delivery outcomes and postpartum conditions

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Insulin

Trial Overview The study compares maternal and neonatal outcomes using strict versus permissive thresholds for starting insulin treatment in gestational diabetes. Strict threshold means two abnormal blood sugar readings in a week; permissive allows up to half the weekly readings to be high before starting insulin.

How Is the Trial Designed?

Group I: Strict Arm Active Control 1 Intervention

The strict threshold is defined as two abnormal values or more over a one-week period (two fasting values elevated, two of the same post prandial values elevated, or 1 fasting and 1 post prandial value elevated)

Group II: Permissive Active Control 1 Intervention

The permissive threshold is defined as 50% of values elevated over 1 week (50% of overall fasting values, 50% of postprandial values, or 50% of overall values).

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

In a study of 50 women with gestational diabetes, approximately 44% developed insulin autoantibodies (IAs) after starting human insulin therapy, indicating that this treatment can trigger an immune response in some patients.

Despite the presence of IAs, there was no significant difference in adverse fetal outcomes between mothers with and without IAs, suggesting that the immunogenic response to insulin may not negatively impact pregnancy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes. Balsells, M., Corcoy, R., Mauricio, D., et al.[2019]

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]

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 of 69 women with Gestational Diabetes Mellitus (GDM), those who received exogenous insulin (Group B) showed significantly higher placental weight, cord width, and baby weight compared to those on diet control alone (Group A), indicating improved fetal growth.

The use of insulin also influenced delivery methods, with a higher number of cesarean sections in the insulin group, suggesting that insulin treatment may impact maternal outcomes as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of insulin on placental, fetal and maternal outcomes in gestational diabetes mellitus. Arshad, R., Karim, N., Ara Hasan, J.[2021]

In a study of 102 women with type 1 diabetes mellitus (T1DM) using insulin glargine during pregnancy, the average HbA1c levels were well-controlled at 6.7% in the first trimester and 6.2% in the third trimester, indicating effective blood sugar management.

The use of insulin glargine was associated with a low rate of severe congenital malformations (2%) and a single stillbirth (1%), suggesting that it is a safe option for managing diabetes in pregnant women without increasing the risk of major birth defects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of insulin glargine throughout pregnancy in 102 women with type 1 diabetes. Lepercq, J., Jacqueminet, S., Hieronimus, S., et al.[2015]

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]

A comprehensive review of 50 studies over the past 20 years revealed significant differences in bioactivity between human insulin and various insulin analogues, affecting metabolism, cell growth, and other cellular functions.

The clinical implications of these differences in bioactivity are still unclear and require further investigation to understand their impact on different patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. Werner, H., Chantelau, EA.[2021]

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]

A comparison of insulin lispro and regular human insulin (Humulin R) in 3634 patients with type 1 and type 2 diabetes showed no significant differences in treatment-emergent adverse events, indicating similar safety profiles for both insulins.

Both insulin therapies did not differ in their effects on the progression of chronic diabetes complications, such as retinopathy, neuropathy, cardiovascular disease, or kidney disease, suggesting that insulin lispro is as safe as Humulin R.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. Glazer, NB., Zalani, S., Anderson, JH., et al.[2019]

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]

In a study of 217 patients with gestational diabetes mellitus (GDM), metformin was found to be as effective as insulin in managing birth weight and other neonatal and maternal outcomes.

About 20.9% of patients on metformin required additional insulin, with higher baseline serum fructosamine levels indicating a greater risk for needing extra insulin, suggesting that serum fructosamine could be a useful predictor for treatment adequacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. Tertti, K., Ekblad, U., Koskinen, P., et al.[2013]

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]

Stricter glycaemic control during pregnancy is still debated, with ongoing trials expected to clarify its impact on perinatal outcomes, suggesting that achieving tighter glucose targets may improve results for mothers and babies.

New insulin formulations, like insulin degludec and glargine (U 300), show promise for better flexibility and control, but current data on their use in pregnancy is limited to case reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucose Targets and Insulin Choice in Pregnancy: What Has Changed in the Last Decade? Bacon, S., Feig, DS.[2019]

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]

Citations

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

Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes. [2019]

2. England 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. [2022]

3. Poland 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]. [2011]

4. Pakistan pubmed.ncbi.nlm.nih.gov

Effects of insulin on placental, fetal and maternal outcomes in gestational diabetes mellitus. [2021]

5. France pubmed.ncbi.nlm.nih.gov

Use of insulin glargine throughout pregnancy in 102 women with type 1 diabetes. [2015]

6. India 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. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years. [2021]

8. England pubmed.ncbi.nlm.nih.gov

The care of pregestational and gestational diabetes and drug metabolism considerations. [2017]

9. England pubmed.ncbi.nlm.nih.gov

Safety of insulin lispro: pooled data from clinical trials. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

Safety of insulin analogs during pregnancy: a meta-analysis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin. [2013]

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

Correlates of Insulin Selection as a First-Line Pharmacological Treatment for Gestational Diabetes. [2023]

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

Glucose Targets and Insulin Choice in Pregnancy: What Has Changed in the Last Decade? [2019]

14. Poland 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]. [2017]