Insulin with or without Metformin for Gestational Diabetes

Overseen By Amanda R Urban, MS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: University of Virginia

Must be taking: Metformin

Disqualifiers: Metformin allergy, Insulin hypersensitivity, Hepatic dysfunction, Kidney disease, 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: Up to 20 weeks

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to manage gestational diabetes, a type of diabetes that occurs during pregnancy. Researchers aim to determine if continuing the medication metformin, along with adding insulin, controls blood sugar better than switching to insulin alone. They believe this approach might reduce the amount of insulin needed and improve health outcomes for both mother and baby. The trial seeks pregnant women with gestational diabetes whose blood sugar isn't controlled by metformin alone and who are willing to try insulin. As a Phase 4 trial, this research involves an FDA-approved treatment and aims to understand its benefits for more patients, offering participants a chance to contribute to improving care for others.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it focuses on whether to continue or stop metformin when starting insulin. It seems you may need to continue metformin if you are already taking it.

What is the safety track record for insulin and metformin?

Research has shown that using metformin with insulin for gestational diabetes is generally safe. Studies have found that this combination effectively manages blood sugar levels without increasing long-term risks for mothers or babies. In fact, using metformin with insulin might lower certain pregnancy-related risks compared to insulin alone. This makes metformin a well-tolerated choice when added to insulin treatment for managing gestational diabetes. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about using metformin alongside insulin for gestational diabetes because it could offer better blood sugar control for pregnant women who don't achieve adequate results with metformin alone. Typically, gestational diabetes is managed with insulin when medications like metformin aren't enough. However, combining metformin with insulin might enhance insulin sensitivity and help maintain stable glucose levels with potentially fewer insulin doses. This combination approach could provide a more effective and convenient management option for expectant mothers struggling to control their blood sugar.

What evidence suggests that continuing metformin with insulin could be effective for gestational diabetes?

Research has shown that using metformin with insulin can effectively treat gestational diabetes. In this trial, one group of participants will receive insulin alone, while another group will receive a combination of metformin and insulin. Studies have found that this combination helps control blood sugar levels and reduces inflammation in the body. Specifically, one study suggested that starting treatment with metformin may lower the risk of negative pregnancy outcomes compared to using only insulin. A review of several studies found that metformin reduces the risk of some problems for mothers and newborns compared to insulin alone. These findings suggest that using metformin with insulin might provide better results for mothers and their babies. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for pregnant individuals diagnosed with gestational diabetes who initially manage their blood sugar levels with metformin but need to start insulin therapy. Specific eligibility details are not provided, so participants should consult the study team for inclusion and exclusion criteria.

Inclusion Criteria

Willing to take blood sugars 4 times per day

Provision of signed and dated informed consent form

I am willing to take insulin if required.

Exclusion Criteria

Pregnancy with major fetal anomalies

Non-viable pregnancy

I have severe liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either continue metformin with insulin or discontinue metformin when insulin is added

Up to 20 weeks

Regular prenatal visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Insulin
• Metformin

Trial Overview The study is testing whether continuing metformin alongside starting insulin therapy offers benefits over stopping metformin when beginning insulin. The goal is to see if this combination can reduce how much insulin is needed and lead to better health outcomes for both mother and baby.

How Is the Trial Designed?

Group I: Insulin Active Control 1 Intervention

Pregnant women with gestational diabetes who have uncontrolled blood sugar on metformin along will be started on insulin and metformin will be discontinued.

Group II: Metformin + Insulin Active Control 1 Intervention

Pregnant women with gestational diabetes who have uncontrolled blood sugar on metformin alone will be started on insulin and will stay on metformin.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

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]

Metformin is a safe and effective treatment for gestational diabetes, but some women may still need additional insulin to control their blood sugar levels.

The study found that starting metformin therapy earlier in pregnancy is linked to a lower likelihood of needing supplemental insulin, suggesting timing may play a crucial role in managing gestational diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes. McGrath, RT., Glastras, SJ., Hocking, S., et al.[2022]

In a study of 71 women with gestational diabetes, metformin treatment resulted in better glycemic control compared to insulin, with significantly lower fasting blood sugar levels and HbA1C at term.

Metformin was associated with improved feto-maternal outcomes, including fewer cesarean sections and lower birth weights, while insulin treatment led to higher rates of complications such as intrauterine deaths and larger newborn sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feto-maternal outcomes and Glycemic control in Metformin versus insulin treated Gestational Diabetics. Arshad, R., Khanam, S., Shaikh, F., et al.[2022]

In a study of 7268 pregnancies, metformin treatment for gestational diabetes mellitus (GDM) was associated with a lower risk of planned elective cesarean sections, large for gestational age infants, and neonatal hypoglycemia compared to insulin treatment.

There were no significant differences in average birthweight between the two treatment groups, suggesting that metformin is an effective alternative to insulin without compromising neonatal weight outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand. Landi, SN., Radke, S., Boggess, K., et al.[2020]

In a study of 63 women with gestational diabetes mellitus (GDM), metformin was found to be an effective alternative to insulin, with no significant differences in glycemic control or neonatal outcomes between the two treatments.

The majority of women treated with metformin (27 out of 32) were successfully managed on a low dosage of 500 mg twice a day, indicating that metformin can be a safe and effective option for controlling GDM without the need for insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. Moore, LE., Briery, CM., Clokey, D., et al.[2022]

In a study of 1269 women with gestational diabetes, those treated with metformin experienced fewer adverse maternal and neonatal outcomes compared to those treated with insulin, including lower rates of Caesarean deliveries and preterm births.

While metformin treatment was associated with better outcomes, it is important to note that women on insulin had higher baseline BMIs and fasting glucose levels, which may have influenced the results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin for gestational diabetes in routine clinical practice. Goh, JE., Sadler, L., Rowan, J.[2022]

In a study involving 200 women with gestational diabetes, metformin provided better postprandial glycemic control compared to insulin, particularly after lunch and dinner, while also resulting in significantly fewer hypoglycemic episodes (17.7% for metformin vs. 55.9% for insulin).

Metformin treatment was associated with less maternal weight gain and lower rates of labor inductions (45.7% vs. 62.5%) and cesarean deliveries (27.6% vs. 52.6%) compared to insulin, with similar obstetrical and perinatal outcomes between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial. Picón-César, MJ., Molina-Vega, M., Suárez-Arana, M., et al.[2022]

A meta-analysis of 21 studies involving 4,545 patients found that metformin significantly reduces maternal weight gain, gestational hypertension, and the risk of maternal hypoglycemia compared to insulin during pregnancy.

While metformin shows benefits for maternal and neonatal outcomes, it also increases the risk of small for gestational age infants, highlighting the need for further long-term studies on the effects of in utero exposure to metformin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of metformin alone or as an add-on therapy to insulin in pregnancy with GDM or T2DM: A systematic review and meta-analysis of 21 randomized controlled trials. He, K., Guo, Q., Ge, J., et al.[2022]

Among 12,631 women with preexisting type 2 diabetes mellitus (T2DM), insulin use during pregnancy remained stable at 55%-60% in the second trimester, while metformin use increased significantly from less than 5% to 20%.

The study indicates a trend towards increased use of insulin-metformin combinations and other noninsulin antidiabetic agents during pregnancy, highlighting the need for further safety studies on these medication regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of glucose-lowering medications for the treatment of type 2 diabetes mellitus during pregnancy in the United States. Wood, ME., Patorno, E., Huybrechts, KF., et al.[2022]

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 324 women with gestational diabetes (GDM) treated with metformin, there was a significant reduction in the rates of macrosomic babies (12.7% vs. 20%) and small for gestational age (SGA) infants (7.7% vs. 14.3%) compared to 175 women treated with diet alone.

Metformin was shown to be effective in improving pregnancy outcomes for women with GDM, even in those with more severe glucose intolerance at the start of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregnancy outcomes after metformin treatment for gestational diabetes: a case-control study. Balani, J., Hyer, S., Johnson, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10642422/

Effects of insulin aspart and metformin on gestational ... Insulin aspart combined with metformin are effective for treatment of GDM, which can reduce blood-glucose-related indexes, Hcy and serum inflammatory cytokines.

2. dom-pubs.onlinelibrary.wiley.com dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.16115

Metformin and risk of adverse pregnancy outcomes among ... Our study suggests that, compared to initiating insulin, initiating metformin is associated with decreased risks of adverse pregnancy outcomes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06445946?aggFilters=phase%3A4+3%2CstudyType%3Aint

A Comparative Effectiveness Trial of Metformin Versus ... To evaluate whether pregnant individuals randomized to metformin have equivalent patient-reported outcomes (PROs), as measured at 6 weeks postpartum and at 2 ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/14767058.2023.2295809

A meta-analysis of metformin and insulin on maternal ... The findings suggest that metformin can reduce the risk of certain maternal and neonatal outcomes compared with insulin therapy for GDM.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa0707193

Metformin versus Insulin for the Treatment of Gestational ... The rates of the primary outcome did not differ between women treated with metformin alone and those treated with supplemental insulin (29.7% ...

6. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2812641

Metformin Plus Insulin for Preexisting Diabetes or ... This randomized clinical trial compares the effect of insulin plus metformin vs insulin and placebo in reducing the odds of adverse neonatal ...

7. drc.bmj.com drc.bmj.com/content/10/1/e002363

Metformin in pregnancy and risk of adverse long-term ... This study found no increased long-term risk associated with pregnancy exposure to metformin (alone or in combination with insulin), compared with insulin.