Insulin Glargine vs NPH for Diabetes in Pregnancy

Overseen By Joana Lopes Perdigao, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Loyola University

Must be taking: Insulin

Must not be taking: Oral antihyperglycemics

Disqualifiers: Type 1 diabetes, Insulin pump, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Throughout pregnancy

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of insulin, Glargine (also known as Insulin glargine or Lantus) and NPH (Neutral protamine Hagedorn insulin), to determine which manages diabetes more effectively during pregnancy. The goal is to assess whether Glargine, less studied in pregnant women, is as effective and safe as NPH. Women diagnosed with gestational diabetes or Type 2 diabetes during pregnancy who require insulin treatment might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to important research on diabetes management during pregnancy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it focuses on comparing two types of insulin for diabetes in pregnancy. If you are using insulin, you may need to switch to one of the study insulins (Glargine or NPH).

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

Research has shown that insulin glargine is safe for use during pregnancy, with studies finding no safety issues for pregnant women using it to control blood sugar. This makes it a viable option for managing diabetes while pregnant.

Insulin NPH is also considered safe during pregnancy. The FDA currently regards it as low risk. However, reports suggest that up to 45% of pregnant women using NPH might experience severe low blood sugar episodes.

Both insulin glargine and NPH show no major differences in safety or outcomes when used during pregnancy, indicating that both treatments are generally well-tolerated and safe for expectant mothers managing diabetes. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because insulin glargine and insulin NPH offer different ways to manage diabetes in pregnancy. Insulin glargine is a long-acting insulin that provides a steady release, which could mean fewer blood sugar spikes and more stable blood glucose levels throughout the day. Meanwhile, insulin NPH is an intermediate-acting insulin that has been a standard choice for managing diabetes during pregnancy. By comparing these two, researchers hope to determine which one offers the best balance of safety and effectiveness for both the mother and baby.

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

This trial will compare Insulin Glargine and Insulin NPH for managing diabetes during pregnancy. Research has shown that both Insulin Glargine and Insulin NPH effectively manage diabetes during pregnancy. Studies have found no major differences in health outcomes for mothers and babies between these two types of insulin. Insulin Glargine is safe for pregnant women needing blood sugar control. Similarly, Insulin NPH effectively maintains healthy blood sugar levels, preventing problems for both mother and baby. Overall, insulin remains the main treatment for diabetes during pregnancy, helping to maintain stable blood sugar levels and ensuring the health of both mother and child. ^{1 4 6 7 8}

Who Is on the Research Team?

Joana Lopes Perdigao, MD

Principal Investigator

Loyola University

Are You a Good Fit for This Trial?

This study is for pregnant individuals with Type 2 Diabetes or Gestational Diabetes needing insulin. Participants should be those who haven't had adequate studies on the use of Glargine during pregnancy, as current practices vary and NPH insulin is commonly used despite its drawbacks.

Inclusion Criteria

Insulin started prior to 34 weeks gestation

Established prenatal care by 14 weeks gestation

I need to start insulin for diabetes during my pregnancy.

Exclusion Criteria

I use an insulin pump for my diabetes management.

I am under 18 years old.

I am allergic to insulin.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either Insulin Glargine or Insulin NPH dosed 1-2 times daily throughout pregnancy for management of diabetes mellitus.

Throughout pregnancy

Routine prenatal care visits with maternal fetal medicine/high risk obstetric clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for hypoglycemia and fetal growth.

Until delivery

Routine ultrasound with serial growth ultrasounds and antenatal fetal surveillance

What Are the Treatments Tested in This Trial?

Interventions

• Insulin glargine
• Insulin NPH

Trial Overview The trial aims to compare two types of insulin: Glargine and NPH. It's designed to see which one is better for managing diabetes in pregnancy, considering that outside of pregnancy, Glargine tends to cause fewer low blood sugar episodes than NPH.

How Is the Trial Designed?

Group I: Insulin Glargine Active Control 1 Intervention

Insulin Glargine dosed 1-2 times daily throughout pregnancy for management of diabetes mellitus.

Group II: Insulin NPH Active Control 1 Intervention

Insulin NPH dosed 1-2 times daily throughout pregnancy for management of diabetes mellitus.

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

Approved in European Union as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in United States as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in Canada as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in Japan as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in China as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Approved in Switzerland as Lantus for:

• Type 1 diabetes mellitus
• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Loyola University

Lead Sponsor

Trials

161

Recruited

31,400+

Published Research Related to This Trial

In a case study of a 52-year-old man with type 2 diabetes and severe insulin resistance, switching from insulin glargine to NPH insulin resulted in a significant reduction in hemoglobin A1c from 9.5% to 6.1% over 3 months, indicating better glucose control.

The improvement in glucose levels was sustained for a year without major hypoglycemic events, suggesting that NPH insulin may be more effective than insulin glargine for patients with severe insulin resistance, although further randomized studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin glargine or neutral protamine Hagedorn in patients with severe insulin resistance: Is there a benefit? Bota, VM., Hirsch, IB.[2022]

In a study of 52 diabetic pregnant patients, both insulin glargine and NPH insulin provided similar glycemic control, as indicated by hemoglobin A1C levels and blood sugar values.

Maternal and neonatal outcomes, including delivery mode, birth weight, and neonatal health, were comparable between the two insulin treatments, suggesting that insulin glargine is a safe and effective option for managing diabetes in pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin glargine versus neutral protamine Hagedorn insulin for treatment of diabetes in pregnancy. Smith, JG., Manuck, TA., White, J., et al.[2022]

Switching from insulin glargine (IG) to neutral protamine Hagedorn (NPH) insulin resulted in more than double the rate of severe hypoglycemia, indicating a safety concern with NPH insulin.

Patients using IG experienced better blood glucose control, with a significant decrease in glycated hemoglobin (A1C) levels compared to those on NPH, and reported higher treatment satisfaction according to the Diabetes Treatment Satisfaction Questionnaire.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Replacing Insulin Glargine with Neutral Protamine Hagedorn (NPH) Insulin in a Subpopulation of Study Subjects in the Action to Control Cardiovascular Risk in Diabetes (ACCORD): Effects on Blood Glucose Levels, Hypoglycemia and Patient Satisfaction. Berard, L., Cameron, B., Woo, V., et al.[2015]

In a 24-week study involving 162 Chinese children with type 1 diabetes, insulin glargine was found to be effective in reducing HbA1c levels, with a mean change of -0.25% compared to -0.54% for NPH insulin.

Insulin glargine was associated with a lower rate of symptomatic hypoglycemia compared to NPH insulin, indicating it may be a safer option for managing diabetes in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised, open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus. Liu, M., Zhou, Z., Yan, J., et al.[2022]

Patients with Type 1 diabetes reported significantly higher treatment satisfaction with insulin glargine compared to Neutral Protamine Hagedorn (NPH) over the course of the study, with a notable improvement in satisfaction scores (+1.27 for glargine vs. -0.56 for NPH).

Insulin glargine was associated with a lower perceived frequency of hyperglycaemia without increasing the perceived frequency of hypoglycaemia, indicating a safer profile in terms of blood sugar management compared to NPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment satisfaction and psychological well-being with insulin glargine compared with NPH in patients with Type 1 diabetes. Witthaus, E., Stewart, J., Bradley, C.[2022]

In a study of 1,011 patients with type 2 diabetes, switching from NPH insulin to insulin glargine resulted in a significant reduction in HbA1c levels over 4-8 months, indicating improved glycaemic control.

The increase in insulin glargine dosage did not lead to a rise in hypoglycaemic episodes or weight gain, suggesting that glargine is a safe and effective alternative to NPH insulin in everyday clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of switching from NPH insulin to insulin glargine in patients with type 2 diabetes: the retrospective, observational LAUREL study in Italy. Bellia, A., Babini, AC., Marchetto, PE., et al.[2022]

NPH insulin is an intermediate-acting insulin, while insulin glargine is a long-lasting insulin, showing distinct time-action profiles in normal dogs.

Co-administration of NPH insulin and insulin glargine improved glycemic control in insulin-dependent diabetic dogs compared to NPH alone, but it also led to hypoglycemia at the tested dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of time-action profiles of insulin glargine and NPH insulin in normal and diabetic dogs. Mori, A., Sako, T., Lee, P., et al.[2021]

A meta-analysis of 8 studies involving 702 pregnant women (331 using insulin glargine and 371 using NPH insulin) found no significant differences in safety and efficacy outcomes between insulin glargine and NPH insulin for managing diabetes during pregnancy.

Both insulin glargine and NPH insulin showed similar maternal and neonatal outcomes, indicating that glargine is a safe alternative for insulin therapy in pregnant women with gestational or pregestational diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy. Lepercq, J., Lin, J., Hall, GC., et al.[2021]

In a pooled analysis of five randomized controlled trials involving 2,695 participants, adding insulin glargine to oral antidiabetic drugs resulted in greater reductions in HbA1c and fasting blood glucose for adults aged 65 and older compared to NPH insulin.

Both insulin glargine and NPH insulin had similar rates of daytime hypoglycemia, but insulin glargine was associated with lower rates of nocturnal symptomatic and severe hypoglycemia, indicating it may be a safer option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of safety and efficacy of insulin glargine and neutral protamine hagedorn insulin in older adults with type 2 diabetes mellitus: results from a pooled analysis. Lee, P., Chang, A., Blaum, C., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11965006/

Insulin glargine 300 U/mL safety data in pregnancy - PMC The results of our recent analysis of global PV data suggest that Gla‐300 could be used for glycaemic control in pregnant women with diabetes.

2. 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.

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

Meta-Analysis of Maternal and Neonatal Outcomes ... No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during 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 ... A meta-analysis of 11 RCTs demonstrated that metformin treatment in pregnancy does not reduce the risk of GDM in high-risk individuals with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S187140212100014X

Use of insulin glargine during pregnancy: A review Insulin glargine can be continued safely during pregnancy in women who are already taking it prior to pregnancy and have achieved good glycemic control with it.

6. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/am-pdf/10.1111/dom.16295

Insulin glargine 300 U/mL safety data in pregnancy The results of our recent analysis of global PV data suggest that. Gla-300 could be used for glycaemic control in pregnant women with diabetes.

7. diabetesjournals.org diabetesjournals.org/diabetes/article/71/Supplement_1/1056-P/146119/1056-P-Reported-Pregnancy-Outcomes-with-Insulin

1056-P: Reported Pregnancy Outcomes with Insulin Glargine ... The results indicate no safety issues with insulin glargine use during pregnancy. J. Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2797979/

Insulin Glargine Safety in Pregnancy Although there have been few reports on the safety of insulin glargine in pregnancy, several case series and small case-control studies have been reported (17– ...