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

56 Participants Needed

Trial Summary

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 data supports the idea that Patient vs Provider-led Insulin Titration for Gestational Diabetes is an effective treatment?

The available research shows that patient-led insulin titration can be as effective as provider-led titration for managing diabetes, particularly type 2 diabetes. Studies indicate that when patients manage their own insulin adjustments, they achieve similar levels of blood sugar control compared to when healthcare providers make these adjustments. This approach can also reduce delays in starting and adjusting insulin doses, which is important for effective diabetes management. While the studies focus on type 2 diabetes, the principles of patient involvement and timely insulin adjustments could also apply to gestational diabetes, suggesting that patient-led titration might be an effective treatment option. ^{1 2 3 4 5}

What data supports the effectiveness of the drug used in the trial 'Patient vs Provider-led Insulin Titration for Gestational Diabetes'?

Research shows that both patient-led and provider-led insulin management can be effective for controlling blood sugar levels in people with type 2 diabetes, suggesting that similar approaches might be beneficial for gestational diabetes as well. ^{1 2 3 4 5}

What safety data exists for insulin treatment in gestational diabetes?

Existing safety data for insulin treatment in gestational diabetes indicates that insulin analogues such as lispro, aspart, glargine, and detemir are considered safe and effective. These analogues do not cross the placenta and have favorable pharmacokinetic profiles that reduce blood glucose variability and hypoglycemia risk. The FDA has reclassified some of these insulins to category B for use in pregnant women. However, more research is needed, especially for insulins glulisine and degludec, as no controlled trials have been conducted in pregnancy. Overall, insulin analogues are practical options for managing hyperglycemia in pregnancy, with safety and efficacy comparable to human insulin. ^{1 6 7 8 9}

Is insulin therapy safe for use during pregnancy?

Insulin therapy, including insulin analogues like lispro, aspart, and detemir, is generally considered safe for use during pregnancy. These insulins do not cross the placenta and have not been associated with adverse outcomes for mothers or babies. They are often used to manage blood sugar levels in pregnant women with diabetes, reducing the risk of low blood sugar (hypoglycemia). ^{1 6 7 8 9}

Is Patient-led Insulin, Provider-led Insulin a promising drug for gestational diabetes?

Yes, Patient-led Insulin, Provider-led Insulin is a promising drug for gestational diabetes. It allows patients to manage their insulin doses, which can help them achieve better blood sugar control. This approach has been shown to be effective and safe, similar to when doctors manage the insulin doses. It can also help reduce delays in starting insulin treatment, which is important for managing gestational diabetes. ^{1 2 3 8 10}

How does patient-led insulin titration differ from other treatments for gestational diabetes?

Patient-led insulin titration allows individuals to adjust their insulin doses themselves, potentially leading to more timely adjustments and better control of blood sugar levels compared to traditional provider-led methods. This approach can empower patients and may reduce delays in achieving optimal glucose control, which is crucial during pregnancy. ^{1 2 3 8 10}

What is the purpose of this trial?

We propose a pragmatic, unblinded, randomized controlled, single center trial of 56 pregnant individuals with Gestational diabetes mellitus (GDM). Our study proposes a pragmatic randomized control trial of patient led rapid titration of basal insulin compared to standard therapy. There is a planned subgroup analysis of patients with and without concomitant metformin usage. Patients will continue routine clinic visits. Patients who are initiated on basal insulin or started on night-time basal insulin within 7 days will be approached about the study. Patients who agree to be enrolled will sign informed consent.

Research Team

Kartik Venkatesh, MD, PhD

Principal Investigator

Ohio State University

Xiao-Yu Wang, MD

Principal Investigator

Ohio State University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. England 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. [2022]

3. 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]

4. Egypt 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. [2021]

5. England 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. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for hyperglycemia in pregnancy - The new insulins. [2019]

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

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

8. Brazil pubmed.ncbi.nlm.nih.gov

Insulin analogues in the treatment of diabetes in pregnancy. [2019]

9. 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]

10. Pakistan pubmed.ncbi.nlm.nih.gov

Initiation of basal bolus insulin therapy. [2022]