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 trial aims to determine if the diabetes pill metformin is as effective and safe as insulin shots for treating gestational diabetes, which occurs during pregnancy. Researchers seek to compare these treatments regarding pregnancy outcomes and safety for both the pregnant individual and their child up to two years after birth. The trial will also examine differences in personal experiences and preferences between using metformin and insulin. It is suitable for pregnant individuals diagnosed with gestational diabetes who require medication to control their blood sugar levels. As a Phase 4 trial, this research helps to understand how the already FDA-approved metformin benefits more patients.

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.

What is the safety track record for these treatments?

Research has shown that metformin is generally safe during pregnancy. Studies have found no increased risk of birth defects or long-term issues for children. Although some studies have raised concerns about early births and lower birth weights, these results are not consistent across all research. In women with gestational diabetes (GDM), metformin did not increase the risk of having a baby that is too small for their age or early labor.

For insulin, data indicates it poses a low risk during pregnancy. The U.S. Food and Drug Administration has reviewed studies on humans and considers it safe. Research comparing different types of insulin during pregnancy shows no increased risks for mothers or babies. There are no major differences in outcomes between using intermediate and long-acting insulin types.

Both metformin and insulin have been safely used in pregnant individuals with GDM, with no strong evidence of harm to mothers or babies. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Most treatments for gestational diabetes, like insulin, require injections and precise dosing to manage blood sugar levels. However, metformin offers an exciting alternative because it's taken as an oral tablet, which can be more convenient and less invasive than injections. Additionally, metformin works by improving the body's sensitivity to insulin, potentially reducing the need for additional insulin therapy. Researchers are excited about the possibility of using metformin because it could simplify treatment and improve the quality of life for expectant mothers managing gestational diabetes.

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

This trial will compare Metformin and Insulin for gestational diabetes. Research has shown that Metformin, which participants in this trial may receive, can lower the risk of having a baby with a high birth weight and may reduce the chances of the newborn needing extra hospital care. It also helps pregnant individuals gain less weight and lowers the risk of high blood pressure during pregnancy. Metformin does not appear to increase risks for the baby, such as being born too small or too early.

Insulin, another treatment option in this trial, is known to reduce the risks of babies being born too early or with low birth weight. However, babies born to those using Insulin might sometimes have low blood sugar levels. Both treatments are generally safe and effective, each with different benefits and risks. ^{2 5 6 7 8}

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 was diagnosed with gestational diabetes between 20 and 31 weeks of pregnancy.

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

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]

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 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]

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]

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]

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]

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]

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 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]

Citations

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Effectiveness of Insulin Analogs Compared with Human ... The variable that showed favorable results for the use of insulin analogs was gestational age, with a mean difference of - 0.26 (95 % confidence interval [CI]: ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3362948/

Meta-Analysis of Maternal and Neonatal Outcomes ... No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402124002066

Gestational diabetes mellitus - Neonatal and maternal ... Women receiving insulin had a low risk of preterm, low birth weight, and macrosomia. •. Neonatal hypoglycemia was more common in the insulin-treated group. •. 2 ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2828808

Oral Glucose-Lowering Agents vs Insulin for Gestational ... Comparing participants randomized to oral agents vs insulin, there was more reported maternal hypoglycemia (20.9% vs 10.9%, respectively; ...

5. dmsjournal.biomedcentral.com dmsjournal.biomedcentral.com/articles/10.1186/s13098-022-00925-7

Maternal and neonatal outcomes with the use of long acting ... Findings suggest no significant differences in the maternal, perinatal and neonatal outcomes between intermediate and long-acting insulin analogues.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4865394/

Insulin Use in Pregnancy: An Update - PMC - PubMed Central For these insulins, the FDA has received sufficient human data allowing these to be considered low risk in pregnancy.

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15. Management of Diabetes in Pregnancy: Standards of Care ... A meta-analysis of 11 RCTs demonstrated that metformin treatment in pregnancy does not reduce the risk of GDM in high-risk individuals with ...

8. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16295

Insulin glargine 300 U/mL safety data in pregnancy Efficacy, safety and lack of immunogenicity of insulin aspart compared with regular human insulin for women with gestational diabetes mellitus.