Metformin vs Insulin for Gestational Diabetes

(DECIDE Trial)

Recruiting at 20 trial locations

Overseen By Anna Bartholomew, MPH, BS, RN

Age: 18+

Sex: Female

Trial Phase: Phase 4

Sponsor: Ohio State University

Must be taking: Glucose control medications

Disqualifiers: Renal disease, Major fetal malformation, 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: 6

Duration: Duration of pregnancy

1572 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin. This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.

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, since the study involves comparing metformin and insulin for gestational diabetes, you may need to switch to one of these medications if you are currently on a different treatment for glucose control.

Is it safe to use Metformin and Insulin for gestational diabetes?

Insulin analogs like aspart, lispro, glargine, and detemir are considered safe during pregnancy and do not cross the placenta, reducing the risk of adverse effects on the mother and baby. Metformin is also considered safe for milder gestational diabetes, but it does cross the placenta, and long-term safety data is limited. ^{1 2 3 4 5}

How does the drug Metformin compare to Insulin for treating gestational diabetes?

Metformin is unique because it can be taken orally, unlike insulin which requires injections, and it does not increase the risk of low blood sugar (hypoglycemia) as much as insulin does. Studies show that Metformin is as effective as insulin in controlling blood sugar levels in gestational diabetes without significant differences in pregnancy outcomes. ^{6 7 8 9 10}

What data supports the effectiveness of the drug for gestational diabetes?

Research shows that metformin is effective for treating gestational diabetes, with results favoring metformin over insulin in terms of maternal and neonatal outcomes. Additionally, studies indicate that insulin detemir is comparable to other insulin types for managing diabetes during pregnancy. ^{2 11 12 13 14}

Who Is on the Research Team?

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 who require medication. They will be part of a study to compare the effectiveness and safety of metformin, an oral drug, versus insulin injections. Participants will be monitored from pregnancy through two years after birth.

Inclusion Criteria

I can attend follow-up visits for 2 years.

Gestational age at randomization between 20 0/7 - 31 6/7 weeks based on project gestational age

I need medication to control my blood sugar, which has been high recently.

Exclusion Criteria

Major structural malformation of the fetus

My pregnancy test showed a chromosome abnormality in the fetus.

Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included

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 oral metformin or injectable insulin for the treatment of gestational diabetes mellitus (GDM) during pregnancy.

Duration of pregnancy

Regular prenatal visits as per standard care

Postpartum Follow-up

Participants and their children are monitored for safety and effectiveness, including maternal and child health outcomes, up to 2 years postpartum.

2 years

Follow-up visits at 6 weeks postpartum and periodically up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Insulin
• Metformin

Trial Overview The DECIDE trial is testing whether metformin is as effective as insulin in reducing adverse outcomes during pregnancy caused by gestational diabetes. It's a randomized controlled trial where participants are assigned to either the metformin or insulin group randomly.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Metformin as either immediate- or extended-release formulations can be utilized, and titrated to a maximum daily dose of 2,500 mg. Participants receiving metformin will have insulin added only if they have not achieved euglycemia for at least 30% of glucose values after generally receiving the maximum daily dose of metformin of 2,500 mg, or in select situations in the setting of participant intolerance due to mild gastrointestinal symptoms. Participants will be asked to continue taking metformin after treatment supplementation with insulin.

Group II: Insulin Experimental Treatment 1 Intervention

Insulin will be initiated utilizing clinical standards using trimester-specific weight-based dosing criteria, including both basal and prandial insulins for up to a total of 4 daily injections. Consistent with clinical practice, some people may be managed with a single dose of intermediate- or long-acting insulin at night to treat isolated fasting hyperglycemia, while others may require additional treatment of postprandial hyperglycemia with shorter-acting insulin. The sites' insulin formularies include rapid- (Novolog and Humalog), intermediate- (Humulin N, Novolin N, and NPH), and long-acting insulins (Detemir and Lantus).

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

Approved in European Union as Insulin for:

• Diabetes mellitus

Approved in United States as Insulin for:

• Diabetes mellitus

Approved in Canada as Insulin for:

• Diabetes mellitus

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

The George Washington University Biostatistics Center

Collaborator

Trials

27

Recruited

111,000+

Published Research Related to This Trial

In a study of 113 women with type 1 diabetes, both long-acting insulin analogues, detemir and glargine, provided comparable glycaemic control throughout pregnancy, with similar HbA1c levels and rates of severe hypoglycaemia.

The study found that while pregnancy outcomes were generally similar, women using glargine had a lower prevalence of large for gestational age infants compared to those using detemir, suggesting a potential advantage of glargine in this aspect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes: comparison of glycaemic control and pregnancy outcome. Callesen, NF., Damm, J., Mathiesen, JM., et al.[2015]

A case-control study involving 200 women (100 treated with metformin and 100 with insulin) found that metformin treatment for gestational diabetes resulted in more favorable maternal and neonatal outcomes compared to insulin.

The study highlights the safety and efficacy of metformin during pregnancy, suggesting it could be a preferred treatment option, especially considering the financial burden of insulin therapy in developing countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brick by brick: metformin for gestational diabetes mellitus? Ardilouze, JL., Mahdavian, M., Baillargeon, JP.[2019]

Insulin detemir (IDet) is shown to be noninferior to insulin neutral protamine Hagedorn (NPH) for managing gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) in pregnant women, based on a study involving 87 participants.

The study found no significant differences in blood glucose control, maternal weight gain, or perinatal outcomes between the two insulin types, but the NPH group experienced more hypoglycemic events, suggesting IDet may be a safer option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. Herrera, KM., Rosenn, BM., Foroutan, J., et al.[2016]

In a study of 150 women with gestational diabetes, those treated with metformin alone or metformin plus insulin experienced significantly less maternal weight gain and lower rates of preeclampsia compared to those treated with insulin alone.

Metformin treatment also resulted in lower mean birth weights and reduced neonatal morbidity, indicating it is an effective and safe option for managing gestational diabetes, with or without supplemental insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin versus insulin treatment in gestational diabetes in pregnancy in a developing country: a randomized control trial. Ainuddin, J., Karim, N., Hasan, AA., et al.[2018]

In a meta-analysis of 23 trials involving 4533 individuals, metformin was found to be more effective than glyburide in reducing postprandial blood glucose levels in women with gestational diabetes mellitus (GDM).

Metformin also demonstrated a lower prevalence of neonatal hypoglycemia and preeclampsia compared to insulin, along with reduced birth weight and maternal weight gain, making it a promising option for managing GDM and preventing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis. Yu, DQ., Xu, GX., Teng, XY., et al.[2022]

In a review of 24 studies involving 3734 pregnant women with diabetes, insulin analogs aspart, glargine, and detemir were found to be safe, showing no increase in complications for mothers or fetuses.

Lispro was associated with higher birth weights and an increased incidence of large for gestational age (LGA) births compared to regular insulin, indicating a need for careful monitoring when using this treatment during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of insulin analogs during pregnancy: a meta-analysis. Lv, S., Wang, J., Xu, Y.[2022]

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]

Intensive lifestyle modifications are the first step in managing gestational diabetes mellitus (GDM), but when these are insufficient, rapid-acting insulin analogues like aspart and lispro are effective in achieving glycemic control with a lower risk of hypoglycemia compared to regular insulin.

While insulin remains the primary treatment for GDM, oral antihyperglycemic drugs like metformin and glyburide show efficacy but raise safety concerns, particularly regarding their effects on fetal outcomes, highlighting the need for careful consideration in their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Gestational Diabetes Mellitus. Mukerji, G., Feig, DS.[2018]

Insulin analogs like aspart and lispro are safe for use during pregnancy, showing no adverse effects on mothers or fetuses, while improving blood sugar control and reducing hypoglycemic episodes.

Insulin glargine is not recommended during pregnancy, but studies indicate it has a similar risk of congenital malformations as human insulin, based on data from 335 pregnancies with type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin analogs and pregnancy: an update. Torlone, E., Di Cianni, G., Mannino, D., et al.[2015]

In a study of 28 women with preexisting type 2 and early A2 gestational diabetes, metformin was found to be as effective as insulin for glycemic control, with no significant differences in glucose measures between the two groups.

Women treated with metformin experienced significantly fewer episodes of hypoglycemia compared to those on insulin, suggesting that metformin may be a safer option for managing diabetes during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. Hickman, MA., McBride, R., Boggess, KA., et al.[2013]

In a study of 159 South Indian women with gestational diabetes, metformin was associated with significantly better neonatal outcomes compared to glibenclamide, with a primary outcome occurrence of 18.9% in the metformin group versus 35% in the glibenclamide group.

The glibenclamide group experienced a higher rate of neonatal hypoglycaemia (12.5%) compared to none in the metformin group, indicating that metformin may be a safer option for managing gestational diabetes in terms of neonatal health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide--a randomised controlled trial. George, A., Mathews, JE., Sam, D., et al.[2015]

In a study of 25 women with gestational diabetes mellitus (GDM) who started metformin therapy, 64% achieved good blood sugar control, while 36% required insulin due to inadequate control or intolerance.

Fasting glucose levels during an oral glucose tolerance test were key predictors of metformin response; women with fasting glucose ≤5.2 mmol/L had a 93% chance of responding well to metformin, highlighting the importance of monitoring glucose levels in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fasting blood glucose predicts response to extended-release metformin in gestational diabetes mellitus. Corbould, A., Swinton, F., Radford, A., et al.[2014]

In a study of 150 pregnant women with gestational diabetes, metformin was found to be as effective as insulin in controlling blood sugar levels, indicating it is a viable alternative for managing GDM.

Metformin use resulted in fewer instances of maternal hypoglycemia compared to insulin, suggesting it may be a safer option for mothers while still achieving good neonatal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Could Metformin Manage Gestational Diabetes Mellitus instead of Insulin? Saleh, HS., Abdelsalam, WA., Mowafy, HE., et al.[2022]

In a study involving 100 women with gestational diabetes mellitus (GDM), both insulin regimens (Novo-rapid + Levemir and Regular + NPH) effectively controlled blood glucose levels, showing no significant differences in efficacy between the two groups.

However, the Novo-rapid and Levemir insulin regimen was associated with higher patient satisfaction and shorter hospitalization times, making it the preferred treatment option for managing GDM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin in glycemic control in gestational diabetes. Amini, FG., Nia, AF., Sharbafi, MH., et al.[2020]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes: comparison of glycaemic control and pregnancy outcome. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Brick by brick: metformin for gestational diabetes mellitus? [2019]

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

Randomized controlled trial of insulin detemir versus NPH for the treatment of pregnant women with diabetes. [2016]

4. Ireland pubmed.ncbi.nlm.nih.gov

Metformin versus insulin treatment in gestational diabetes in pregnancy in a developing country: a randomized control trial. [2018]

5. England pubmed.ncbi.nlm.nih.gov

Glycemic control and neonatal outcomes in women with gestational diabetes mellitus treated using glyburide, metformin, or insulin: a pairwise and network meta-analysis. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

Safety of insulin analogs during pregnancy: a meta-analysis. [2022]

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

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

8. New Zealand pubmed.ncbi.nlm.nih.gov

Pharmacological Management of Gestational Diabetes Mellitus. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Insulin analogs and pregnancy: an update. [2015]

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

Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. [2013]

11. Australia pubmed.ncbi.nlm.nih.gov

Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide--a randomised controlled trial. [2015]

12. Australia pubmed.ncbi.nlm.nih.gov

Fasting blood glucose predicts response to extended-release metformin in gestational diabetes mellitus. [2014]

13. Egypt pubmed.ncbi.nlm.nih.gov

Could Metformin Manage Gestational Diabetes Mellitus instead of Insulin? [2022]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin in glycemic control in gestational diabetes. [2020]