Insulin Management Strategies for Diabetes during Pregnancy

Recruiting at 3 trial locations

Overseen By Ashley Battarbee, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must be taking: Insulin, Metformin

Disqualifiers: Major fetal anomaly, Triplet, others

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

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications. However, it involves testing different insulin strategies, so you may need to adjust your insulin treatment.

What data supports the effectiveness of insulin therapy for managing diabetes during pregnancy?

Research shows that flexible, intensive insulin management improves blood sugar control and treatment satisfaction in type 1 diabetes, which suggests that similar strategies could be beneficial for managing diabetes during pregnancy. ^{1 2 3 4 5}

Is insulin management during pregnancy safe for women with diabetes?

Research shows that while antenatal corticosteroids like betamethasone can help reduce complications in newborns, they may cause high blood sugar levels in pregnant women with diabetes. This suggests that careful monitoring and management of insulin are important to ensure safety during pregnancy. ^{6 7 8 9 10}

How does the drug antenatal corticosteroids differ from other treatments for diabetes during pregnancy?

Antenatal corticosteroids like betamethasone are unique because they are used to reduce complications in preterm births, but they can cause high blood sugar levels, requiring careful insulin management in pregnant women with diabetes. ^{6 10 11 12 13}

What is the purpose of this trial?

There is a fundamental gap in understanding the maternal and neonatal effects of antenatal corticosteroid (ACS) administration in women with threatened preterm birth (PTB) who have diabetes. Since the initial discovery of ACS for neonatal benefit in 1972, more than 40 randomized controlled trials have been performed evaluating its efficacy. However, none of these trials have included women with T2DM, and there is limited data among women with gestational diabetes. While ACS have been shown to reduce neonatal morbidity associated with PTB in non-diabetic women, the side effects of ACS (maternal hyperglycemia and fetal hyperinsulinemia) may mitigate the neonatal benefit of ACS in women with diabetes. Before neonatal benefit of ACS can be evaluated in this population, the first step is to optimize maternal glycemic control after ACS. Previous studies evaluating maternal hyperglycemia after ACS have been limited by small sample size, retrospective study design, or insufficient glucose data. Use of continuous glucose monitoring (CGM) in a randomized clinical trial provides a unique opportunity to overcome these challenges. Our long-term goal is to improve maternal and child health among women with diabetes as an independently funded clinical researcher. The research objectives of this proposal are to test the efficacy of three treatment strategies at achieving maternal glycemic control after ACS and evaluate the association between maternal glycemic control and neonatal outcomes. Our central hypothesis is that treatment with a continuous insulin infusion will improve maternal glycemic control, which is key to improving neonatal outcomes, but at the cost of less patient satisfaction and more health resource utilization. This hypothesis will be tested by pursuing the following specific aims: 1) Test the efficacy of three treatment strategies (addition of sliding scale insulin, up-titration of home insulin, and continuous insulin infusion) at achieving maternal glycemic control after ACS and 2) Quantify the association between maternal glycemic control after ACS and neonatal morbidity. Completion of these aims will determine the optimal strategy to achieve maternal glycemic control after ACS and inform a larger, multicenter trial to improve neonatal outcomes among women with diabetes and threatened PTB.

Research Team

Ashley Battarbee, MD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for pregnant women aged 18-50 with gestational or pregestational type 2 diabetes, treated with insulin injections or medications like metformin. They must be hospitalized for corticosteroid administration due to the risk of premature birth between weeks 23 and almost 37 of pregnancy.

Inclusion Criteria

I am a woman aged between 18 and 50.

You are between 23 weeks and 36 weeks pregnant.

Hospitalized for antenatal corticosteroid administration in anticipation of preterm birth

Exclusion Criteria

You are planning to give birth within 72 hours after receiving the first dose of antenatal corticosteroids.

Triplet or higher order multiple gestation

The participant has a major abnormality in the unborn baby.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of three insulin treatment strategies for glycemic control after antenatal corticosteroids

5 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including completion of the Diabetes Treatment Satisfaction Questionnaire

1 week

Delivery and Neonatal Monitoring

Umbilical cord blood is collected at delivery, and neonates are monitored for glucose levels and respiratory morbidity

Birth to hospital discharge, assessed up to 28 days

Treatment Details

Interventions

• Antenatal Corticosteroids
• Continuous Insulin Infusion
• Sliding Scale Insulin
• Up-Titration of Home Insulin

Trial Overview The study tests three strategies to control blood sugar after receiving corticosteroids: adding sliding scale insulin, increasing usual home insulin doses, and giving continuous insulin infusions. It also uses a Dexcom G6 monitor to track glucose levels.

Participant Groups

Group I: Up-Titration of Home Insulin Experimental Treatment 2 Interventions

Increase in home insulin regimen based on standardized algorithm for maximum of 5 days after antenatal corticosteroids

Group II: Sliding Scale Insulin Experimental Treatment 2 Interventions

Addition of supplemental sliding scale insulin to home insulin regimen for maximum of 5 days after antenatal corticosteroids

Group III: Continuous Insulin Infusion Experimental Treatment 2 Interventions

Discontinuation of home insulin regimen and receipt of continuous insulin infusion for maximum of 5 days after antenatal corticosteroids

Antenatal Corticosteroids is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Betamethasone for:

• Antenatal corticosteroid therapy for fetal maturation
• Inflammatory conditions
• Allergic states
• Dermatologic disorders
• Gastrointestinal diseases
• Hematological disorders

Approved in United States as Betamethasone for:

• Antenatal corticosteroid therapy for fetal maturation
• Inflammatory conditions
• Allergic states
• Dermatologic disorders
• Gastrointestinal diseases
• Hematological disorders

Approved in Canada as Betamethasone for:

• Antenatal corticosteroid therapy for fetal maturation
• Inflammatory conditions
• Allergic states
• Dermatologic disorders
• Gastrointestinal diseases
• Hematological disorders

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

Primary care physicians are now primarily responsible for managing diabetes and insulin therapy, highlighting the need for clear, evidence-based guidelines to assist in treatment.

For patients with type 2 diabetes who have not achieved target blood glucose levels after using two oral medications, initiating insulin therapy with a basal insulin analog is recommended, along with simplified regimens for insulin titration and follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. LaSalle, JR., Berria, R.[2022]

Flexible, intensive insulin management using new insulin analogues significantly improves glycemic control and allows for greater dietary freedom in individuals with type 1 diabetes, particularly benefiting children and adolescents.

Effective implementation of this management approach relies on individualized patient education and collaboration between patients and clinicians, which is crucial for addressing the specific needs and preferences of adolescents with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fairy tale of modern insulin therapy in type 1 diabetes. Papanas, N., Demetriou, M., Maltezos, E.[2021]

Approximately six million people with diabetes rely on insulin for their treatment, but many face significant barriers that lead to poor adherence to their insulin regimens.

There is a lack of effective interventions to improve insulin adherence, highlighting the need for patient involvement in shared decision-making until better insulin options are developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to Insulin Therapy. Sarbacker, GB., Urteaga, EM.[2022]

A pharmacist-led diabetes medication management program (MMP) significantly reduced A1c levels in type 2 diabetic patients over 2 years, with a mean reduction of -1.24 compared to -0.59 in standard care patients (P = 0.009).

The MMP patients had a lower A1c level after 2 years (8.06) compared to control patients (8.67), demonstrating the program's effectiveness in managing diabetes when combined with a copay waiver for medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Glycemic Control of a Pharmacist-Led Medication Management Program in Patients with Type 2 Diabetes. Ko, JJ., Lu, J., Rascati, K., et al.[2023]

The direct medical costs associated with diabetes mellitus have increased over five times from $44 billion to $176 billion annually between 1997 and 2012, primarily due to rising prevalence and care costs.

Despite stable treatment rates for diabetes, there has been a shift towards increased use of oral medications and a stagnation in insulin usage, highlighting challenges in medication management and the need for better patient engagement in diabetes care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Economic implications of type 2 diabetes management. McAdam Marx, C.[2013]

In a study of 59 pregnant women with diabetes receiving betamethasone for anticipated preterm delivery, the protocol for subcutaneous insulin showed preliminary safety, with no serious hypoglycemic incidents reported.

Most hyperglycemic episodes occurred within 48 hours post-betamethasone administration, particularly after meals, highlighting the need for enhanced monitoring of blood glucose levels for 72 hours following treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration. Paulsen, C., Hall, DR., Mason, D., et al.[2021]

The pilot study involving 13 women and 9 clinicians found that both groups found participation acceptable, largely due to the perceived low risk of harm from corticosteroids and the high level of clinical support provided.

Women are more likely to participate in clinical trials when they feel well-informed and supported, while clinicians are more likely to support such trials if they believe it will benefit clinical practice and ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnant women with diabetes and their clinician's experience of participating in a pilot randomised controlled trial of corticosteroid administration in late pregnancy: A qualitative study. Sweet, L., Vasilevski, V., Lynch, LA., et al.[2023]

In a study involving 98 newborn infants whose mothers received either Celestona or Celeston during pregnancy, there was no significant difference in occipitofrontal circumference compared to a control group of 1012 untreated infants, suggesting that these treatments do not adversely affect brain development in terms of head size.

The findings indicate that administering betamethasone to pregnant women to prevent respiratory distress syndrome does not lead to negative outcomes in newborn head circumference, particularly when given more than 7 days before delivery and without placental dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occipitofrontal circumference in newborns of betamethasone treated mothers. Verder, H., Kjer, JJ., Hess, J., et al.[2019]

Antenatal corticosteroid therapy (ACS) has been widely used to promote fetal lung maturation, but current dosing practices may expose fetuses to higher levels of corticosteroids than necessary, which could pose risks.

Research using sheep and monkey models suggests that much lower doses of corticosteroids (around 1 ng/ml) are sufficient for fetal lung maturation, indicating a need for new clinical trials to explore safer dosing strategies, potentially including oral administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antenatal corticosteroids: a reappraisal of the drug formulation and dose. Jobe, AH., Kemp, M., Schmidt, A., et al.[2021]

Antenatal betamethasone treatment in pregnant women with severe diabetes can lead to severe acute complications for both the mother and fetus, raising concerns about its safety in this high-risk group.

While corticosteroids are typically used to prevent complications from prematurity, this study questions their overall benefit in diabetic pregnancies due to potential disturbances in metabolic and blood pressure balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good?]. Barondiot, C., Morel, O., Vieux, R., et al.[2013]

Antenatal corticosteroids (ACS) are effective in reducing risks for mothers at risk of preterm delivery before 34 weeks, but they can cause hyperglycemia, which is a significant side effect.

The review discusses management strategies for glycemic control in pregnant women, including those with pre-existing diabetes, gestational diabetes, and those with normal glucose levels after receiving ACS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic management after antenatal corticosteroid therapy. Kalra, S., Kalra, B., Gupta, Y.[2021]

In a study of 647 women with diabetes who received antenatal corticosteroids, 92% experienced elevated blood glucose levels after treatment, with hyperglycaemia lasting about 72 hours.

Maternal hyperglycaemia within 24 hours of delivery significantly increased the risk of neonatal hypoglycaemia, indicating the need for careful monitoring of blood sugar levels in pregnant women receiving corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maternal and neonatal glycaemic control after antenatal corticosteroid administration in women with diabetes in pregnancy: A retrospective cohort study. Tuohy, JF., Bloomfield, FH., Crowther, CA., et al.[2021]

In a study of 347 women with diabetes in pregnancy, an intravenous insulin protocol effectively maintained maternal glucose levels within the target range after administration of betamethasone, with a high time-in-range of 83%.

Factors such as type of diabetes and late-pregnancy complications were linked to increased insulin requirements, suggesting that personalized glycaemic control strategies could improve outcomes for mothers and their infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors associated with maternal hyperglycaemia and neonatal hypoglycaemia after antenatal betamethasone administration in women with diabetes in pregnancy. Rowe, CW., Rosee, P., Sathiakumar, A., et al.[2023]

References

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

Insulin therapy in type 2 diabetes mellitus: a practical approach for primary care physicians and other health care professionals. [2022]

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

A fairy tale of modern insulin therapy in type 1 diabetes. [2021]

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

Adherence to Insulin Therapy. [2022]

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

Analysis of Glycemic Control of a Pharmacist-Led Medication Management Program in Patients with Type 2 Diabetes. [2023]

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

Economic implications of type 2 diabetes management. [2013]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Observations on Glucose Excursions With the Use of a Simple Protocol for Insulin, Following Antenatal Betamethasone Administration. [2021]

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

Pregnant women with diabetes and their clinician's experience of participating in a pilot randomised controlled trial of corticosteroid administration in late pregnancy: A qualitative study. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Occipitofrontal circumference in newborns of betamethasone treated mothers. [2019]

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

Antenatal corticosteroids: a reappraisal of the drug formulation and dose. [2021]

10. France pubmed.ncbi.nlm.nih.gov

[Antenatal betamethasone during pregnancy with severe diabetes: is better worse than good?]. [2013]

11. India pubmed.ncbi.nlm.nih.gov

Glycemic management after antenatal corticosteroid therapy. [2021]

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

Maternal and neonatal glycaemic control after antenatal corticosteroid administration in women with diabetes in pregnancy: A retrospective cohort study. [2021]

13. England pubmed.ncbi.nlm.nih.gov

Factors associated with maternal hyperglycaemia and neonatal hypoglycaemia after antenatal betamethasone administration in women with diabetes in pregnancy. [2023]