Insulin Therapy for Gestational Diabetes

(START2 Trial)

Recruiting in Rochester (>99 mi)

+1 other 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

Trial Summary

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.

What data supports the effectiveness of insulin therapy for gestational diabetes?

Research shows that insulin analogs like Humalog and insulin detemir are effective in managing blood sugar levels during pregnancy, which is crucial for reducing complications in diabetic women. Studies indicate that these insulins help achieve good metabolic control without adverse effects on mothers or babies. ^{1 2 3 4 5}

Is insulin therapy safe for use during pregnancy and in general?

Research shows that insulin analogs like lispro, aspart, glargine, and detemir are safe during pregnancy, as they do not cross the placenta or cause harm to the mother or baby. These insulins have favorable properties that help maintain stable blood sugar levels, reducing the risk of low blood sugar episodes. ^{6 7 8 9 10}

How does insulin therapy differ from other treatments for gestational diabetes?

Insulin therapy for gestational diabetes is unique because it involves direct administration of insulin to manage blood sugar levels, which can be more effective for those who do not respond well to diet and exercise alone. Unlike metformin, which is an oral medication, insulin can be adjusted more precisely to meet individual needs, especially in cases of high insulin resistance or allergies to specific insulin types. ^{11 12 13 14 15}

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 study arm target range will be 65-120 mg/dL, with time in range goal of 70%. The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

Eligibility Criteria

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

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

Treatment Details

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%.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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 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 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 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]

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]

References

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

Pregnancy complications and perinatal outcome in diabetic women treated with Humalog (insulin lispro) or regular human insulin during pregnancy. [2022]

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

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. [2016]

3. England 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. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Insulin analogs and pregnancy: an update. [2015]

5. 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]

6. United States 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. [2020]

7. 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]

8. England 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. [2015]

9. Germany pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

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

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

Use of insulin pumps in pregnancies complicated by type 2 diabetes and gestational diabetes in a multiethnic community. [2021]

12. 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]

13. 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]

14. Australia pubmed.ncbi.nlm.nih.gov

Fasting blood glucose predicts response to extended-release metformin in gestational diabetes mellitus. [2014]

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

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