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

Trial Summary

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 data supports the effectiveness of the drugs insulin and metformin for gestational diabetes?

Research shows that both metformin and insulin are effective in managing blood sugar levels in women with gestational diabetes. Studies comparing the two drugs found that they both help control blood sugar and have similar outcomes for mothers and babies. ^{1 2 3 4 5}

Is it safe to use insulin and metformin for gestational diabetes?

Research shows that metformin, alone or with insulin, is generally safe for treating gestational diabetes, though some women may need extra insulin. Metformin can pass from mother to baby, but its long-term effects are still unclear. ^{1 5 6 7 8}

How does the drug Metformin differ from other treatments for gestational diabetes?

Metformin is an alternative to insulin for treating gestational diabetes and can lead to similar pregnancy outcomes. However, nearly half of the women using metformin may still need additional insulin to achieve their blood sugar goals. ^{5 8 9 10 11}

What is the purpose of this trial?

This will be a randomized trial of patients with gestational diabetes who start hypoglycemic therapy with metformin but eventually require insulin. It will examine whether continuing metformin when adding insulin versus discontinuing metformin when insulin is added is beneficial. The investigators hypothesize that continuing metformin will reduce the needed insulin dosage and improve maternal and neonatal outcomes in these patients.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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]

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]

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]

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 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 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]

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]

References

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

Metformin for gestational diabetes in routine clinical practice. [2022]

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

Comparative effectiveness of metformin versus insulin for gestational diabetes in New Zealand. [2020]

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

Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. [2022]

4. Pakistan pubmed.ncbi.nlm.nih.gov

Feto-maternal outcomes and Glycemic control in Metformin versus insulin treated Gestational Diabetics. [2022]

5. 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]

6. England 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. [2022]

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

Pregnancy outcomes after metformin treatment for gestational diabetes: a case-control study. [2020]

8. Ireland pubmed.ncbi.nlm.nih.gov

Use of metformin earlier in pregnancy predicts supplemental insulin therapy in women with gestational diabetes. [2022]

9. Australia pubmed.ncbi.nlm.nih.gov

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

10. United States 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. [2022]

11. England 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. [2022]