Patient vs Provider-led Insulin Titration for Gestational Diabetes

Overseen By Xiao-Yu Wang, MD

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Ohio State University

Must be taking: Basal insulin

Disqualifiers: Type 1 or 2 diabetes, 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

Compensation: Varies

Number of Visits: Unknown

Duration: From randomization to delivery, approximately 8-12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two methods for adjusting insulin in pregnant individuals with gestational diabetes. One group will manage their insulin doses (Patient-led Insulin), while the other will follow a doctor's guidance (Provider-led Insulin). The study aims to determine which method better controls blood sugar. Suitable participants have been diagnosed with gestational diabetes, need to start or have just started basal insulin, and are receiving prenatal care at OSU or an affiliated clinic. As a Phase 4 trial, this research explores how an already FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, there is a subgroup analysis for patients using metformin, so you might be able to continue it. Please consult with the trial coordinators for more details.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that patients with gestational diabetes will be starting or have recently started basal insulin, and there is a subgroup analysis for those using metformin.

What is the safety track record for these treatments?

Research has shown that when patients manage their own insulin levels during gestational diabetes, it is both safe and effective. Studies have found that this approach helps maintain blood sugar control and results in babies with healthier birthweights. Although there is a small increase in the risk of low blood sugar, with a relative risk of 1.12, it is not a major concern.

Overall, patients generally manage their insulin well. This method helps achieve lower blood sugar goals quickly, which is crucial for managing gestational diabetes. No major safety issues have been reported, making it a promising option for pregnant individuals managing their blood sugar. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores a new way for patients with gestational diabetes to manage their insulin levels. Unlike the standard approach, where healthcare providers adjust the insulin dosage, this method empowers patients to self-titrate their insulin based on their daily blood glucose readings. This patient-led approach could potentially offer more personalized and timely adjustments to insulin therapy, improving blood sugar control and potentially enhancing overall pregnancy outcomes. By giving patients more control, this method might also increase engagement and adherence to their treatment plan.

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

This trial will compare patient-led insulin titration with provider-led insulin management for gestational diabetes. Research has shown that when pregnant women with gestational diabetes adjust their own insulin doses, it can be effective. Studies have found that these women often use higher insulin doses and achieve better blood sugar control. Specifically, their fasting blood sugar levels improved, dropping to about 4.6 mmol/L compared to 5.1 mmol/L with standard care. This method also correlates with lower birth weights, benefiting both mother and baby. Overall, patient-managed insulin helps maintain more stable blood sugar levels during pregnancy. ^{1 2 4 5 6}

Who Is on the Research Team?

Xiao-Yu Wang, MD

Principal Investigator

Ohio State University

Kartik Venkatesh, MD, PhD

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for pregnant individuals diagnosed with Gestational Diabetes Mellitus (GDM) between 20 to 32 weeks of gestation, needing basal insulin. Participants must be over 18, speak English or Spanish, and receive care at OSU or affiliated clinics. Those with pre-existing Type 1 or Type 2 diabetes, insulin allergies, or non-English/Spanish speakers are excluded.

Inclusion Criteria

You have been diagnosed with gestational diabetes (GDM) during pregnancy based on high blood sugar levels from specific tests.

I am not using insulin or have started it within the last 7 days.

Receiving prenatal care at OSU or an affiliated clinic where Electronic Health Records (EHR) can be accessed

Exclusion Criteria

You are allergic to insulin.

I have type 1 or type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to either patient-led or provider-led titration of basal insulin for glycemic control in gestational diabetes

From randomization to delivery, approximately 8-12 weeks

Routine clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of pregnancy outcomes and satisfaction surveys

From 36 weeks until delivery

What Are the Treatments Tested in This Trial?

Interventions

• Patient-led Insulin
• Provider-led Insulin

Trial Overview The EMPOWER study is testing whether patients can effectively manage their own insulin levels compared to the standard provider-led approach in controlling blood sugar during pregnancy. It's a randomized control trial involving routine clinic visits and subgroup analysis for those also taking metformin.

How Is the Trial Designed?

Group I: Patient-led self-titration of insulin Experimental Treatment 1 Intervention

Individuals randomized to this arm will initiate night-time insulin of 10 units. The type of basal insulin will be left to the discretion of the provider with levemir or glargine preferred over NPH. On day 0 of initiation of insulin, the patient will initiate night-time (or prior to sleep if alternate sleep schedule) insulin of 10 units (glargine, detemir, or NPH). Patient will check their fasting blood glucose in the morning and record their values. If the value is below 70 they will decrease their insulin dosage that night by 2 units; if the value is above 95 they will increase their insulin dosage that night by 2 units; and if the value is between 70 and 95, they will maintain the same insulin dosage that night. The patients will continue this algorithm for the remainder of the pregnancy. If the patient does not have a fasting blood glucose, the patient will maintain the dose of basal insulin at the prior dose.

Group II: Standard of care Active Control 1 Intervention

Individuals randomized to this arm will receive standard care and titration of insulin will be determined by the individual providers.

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

Approved in European Union as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Approved in United States as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Approved in Canada as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Approved in Japan as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Approved in China as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Approved in Switzerland as Insulin for:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes
• Diabetic Ketoacidosis

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

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 six studies involving 12,409 patients with uncontrolled type 2 diabetes, patient-led titration of basal insulin resulted in a higher insulin dose and improved glycemic control (HbA1c decreased by 0.1% and fasting plasma glucose decreased by 5 mg/dL) compared to physician-led titration.

While patient-led titration was effective, it was associated with a slightly increased risk of hypoglycemia and a small weight gain (+0.2 kg), suggesting that while patients can manage their insulin doses effectively, they should be educated about potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of patient-led versus physician-led titration of basal insulin in patients with uncontrolled type 2 diabetes: a meta-analysis of randomized controlled trials. Castellana, M., Procino, F., Sardone, R., et al.[2021]

Insulin analogues like lispro, aspart, and detemir have been found to be effective and safe for treating hyperglycemia in pregnant women, leading to their reclassification by the FDA from category C to category B, indicating a lower risk during pregnancy.

While insulin analogues generally reduce the risk of hypoglycemia compared to human insulin, more research is needed, especially for their use in gestational diabetes and type 2 diabetes, as well as for other analogues like glargine, glulisine, and degludec which lack extensive controlled trial data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for hyperglycemia in pregnancy - The new insulins. Toledano, Y., Hadar, E., Hod, M.[2019]

For patients with type 2 diabetes who are not meeting their blood sugar goals, long-acting or pre-mixed insulin is generally recommended, but there are specific cases where a basal bolus insulin regimen is more appropriate.

The '5S' criteria—Severe hyperglycaemia, Symptomatic diabetes, Sick diabetes, Special situations (like pregnancy), and Secondary diabetes—highlight when to consider starting a basal bolus insulin approach for better management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initiation of basal bolus insulin therapy. Priya, G., Kalra, S., Bahendeka, S., et al.[2022]

In a 24-week study involving 355 insulin-naïve adults with uncontrolled type 2 diabetes, patient-managed (nurse-assisted) titration of insulin glargine 300 U/mL (Gla-300) was found to be as effective as physician-managed titration in reducing HbA1c levels.

Both management approaches had a similarly low incidence of hypoglycemia, indicating that patient-managed titration is a safe and effective option for improving glycemic control in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable efficacy with similarly low risk of hypoglycaemia in patient- vs physician-managed basal insulin initiation and titration in insulin-naïve type 2 diabetic subjects: The Italian Titration Approach Study. Bonadonna, RC., Giaccari, A., Buzzetti, R., et al.[2022]

Pregnancy can induce a diabetogenic effect in women, leading to gestational diabetes in 2% to 14% of cases, which necessitates careful management of blood sugar levels to prevent complications for both mother and fetus.

For women with preexisting diabetes, transitioning to insulin therapy is crucial for maintaining optimal glycemic control during pregnancy, and this review aims to guide healthcare providers in selecting the safest and most effective insulin treatments, including both short- and long-acting analogues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin analogues in the treatment of diabetes in pregnancy. Negrato, CA., Montenegro Junior, RM., Von Kostrisch, LM., et al.[2019]

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]

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]

The review highlights the importance of patient-centered care in managing type 2 diabetes, suggesting alternatives to adding prandial insulin when basal insulin alone is insufficient for glycemic control.

It emphasizes the need for flexible and easy-to-teach treatment regimens, allowing patients and providers to collaboratively choose between options like rapid-acting insulin or short-acting GLP-1 analogs, balancing efficacy, safety, and adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A short-acting GLP-1 analog or prandial insulin to supplement basal insulin?--Moving toward personalized management of type 2 diabetes mellitus. Hirsch, IB., Schneider, D., King, A., et al.[2022]

In a study of 89 pregnant women with type 2 and gestational diabetes, insulin lispro protamine suspension showed similar maternal and neonatal outcomes compared to human NPH insulin, indicating its effectiveness as a treatment option.

Women using insulin lispro required less insulin overall than those on NPH, suggesting it may be a more efficient choice for managing diabetes during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes. Colatrella, A., Visalli, N., Abbruzzese, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9544985/

Patient‐led rapid titration of basal insulin in gestational ... Patient‐led daily insulin titration in gestational diabetes leads to higher insulin dose use lower fasting glucose and is associated with lower birthweight

2. wchh.onlinelibrary.wiley.com wchh.onlinelibrary.wiley.com/doi/10.1002/pdi.2407

In gestational diabetes, patient‐led insulin titration is ... At delivery, patient-led titration achieved higher final insulin doses (53 vs 36 units/day; p=0.027), improved fasting glucose (4.6 vs 5.1mmol/L ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35900879/

Patient-led rapid titration of basal insulin in gestational ... Patient-led daily insulin titration in gestational diabetes leads to higher insulin dose use lower fasting glucose and is associated with lower birthweight ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1871402123000425

Studies are needed to support optimal insulin dose titration ... In this study, patient-led daily basal insulin titration was associated with higher insulin doses, tighter glycaemic control, and lower birthweight.

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/pdi.2407

In gestational diabetes, patient‐led insulin titration is ... At delivery, patient-led titration achieved higher final insulin doses (53 vs 36 units/day; p=0.027), improved fasting glucose (4.6 vs 5.1mmol/L ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/8915315

Rapid, patient-led titration of basal insulin can be used to ... Patient-led insulin titration was associated with a negligible increase in the risk of hypoglycaemia (relative risk (RR)=1.12; 95% CI 1.02 to 1.23) however the ...