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

Trial Summary

What is the purpose of this trial?

We are asking you to take part in this research study because you are diagnosed with pregestational Type 2 Diabetes Mellitus or Gestational Diabetes Mellitus requiring insulin therapy in pregnancy. Currently, many hospitals differ among use of insulin for management of DM in pregnancy, with NPH, glargine and detemir being the most commonly used forms of basal insulin. Outside of pregnancy, NPH is rarely used with glargine and determir being the more common forms of insulin used due to their fewer episodes of hypoglycemia in these patients. Detemir has been well studied in pregnancy and found to be noninferior to NPH. Unfortunately, glargine has not been as well studied in pregnancy. Thus, with this study we want to compare glargine and NPH. The purpose of this study is to compare two different forms of insulin (Glargine and NPH) that we regularly use to manage diabetes mellitus in 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).

What data supports the effectiveness of the drug Insulin Glargine for diabetes in pregnancy?

Research comparing insulin glargine and NPH insulin in diabetic pregnancies showed that both drugs are used to manage blood sugar levels effectively. Additionally, studies in patients with type 2 diabetes suggest that insulin glargine may offer better blood sugar control and fewer episodes of low blood sugar compared to NPH insulin. ^{1 2 3 4 5}

Is insulin glargine safe to use during pregnancy compared to NPH insulin?

Research shows that there are no significant differences in safety between insulin glargine and NPH insulin when used during pregnancy. Both types of insulin are considered safe for managing diabetes in pregnant women. ^{1 2 6 7 8}

How does the drug insulin glargine differ from NPH insulin for diabetes in pregnancy?

Insulin glargine is a long-acting insulin that provides a constant, peakless release, which can lead to fewer episodes of low blood sugar compared to NPH insulin, an intermediate-acting insulin. Both are used to manage blood sugar levels in pregnancy, but studies show no significant differences in safety and efficacy between them during pregnancy. ^{2 3 6 7 9}

Research Team

Joana Lopes Perdigao, MD

Principal Investigator

Loyola University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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 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]

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]

References

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

Insulin glargine versus neutral protamine Hagedorn insulin for treatment of diabetes in pregnancy. [2022]

2. Canada 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. [2015]

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

Insulin glargine or neutral protamine Hagedorn in patients with severe insulin resistance: Is there a benefit? [2022]

4. Germany 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. [2022]

5. United States 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. [2022]

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

Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy. [2021]

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

Treatment satisfaction and psychological well-being with insulin glargine compared with NPH in patients with Type 1 diabetes. [2022]

8. England 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. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of time-action profiles of insulin glargine and NPH insulin in normal and diabetic dogs. [2021]