Metformin In Pregnancy: Safety, Dosage, Side Effects And Alternatives

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Metformin or metformin hydrochloride is a prescription drug available as immediate-release or extended-release oral tablets for treating type 2 diabetes mellitus. Consuming metformin while pregnant helps lower blood glucose levels by improving the body’s response to naturally secreted insulin. It decreases the intestinal absorption of sugars from ingested food and controls the synthesis of sugars in the liver (1) (2).

The drug also has proven benefits in treating polycystic ovary syndrome (PCOS) in women of reproductive age and improving pregnancy outcomes (3). Continue reading this post to learn about the safety and efficacy of metformin during pregnancy.

Is Metformin Safe During Pregnancy?

Metformin may be prescribed before or during pregnancy and is usually considered safe. Scientific studies have not suggested an increased incidence of any congenital anomaly with the use of this medication during pregnancy. The US Food and Drug Administration (FDA) ranks metformin in category B (animal reproduction studies have not demonstrated a fetal risk, and inadequate well-controlled studies have been conducted on pregnant women) (4).

How Does Metformin Help With Pregnancy?

Metformin may be prescribed by doctors when the body does not respond appropriately to the insulin hormone secreted by the pancreatic cells. This phenomenon is known as insulin resistance and is seen in type 2 diabetes mellitus and gestational diabetes (high blood glucose during pregnancy). The condition is also encountered in PCOS, a major cause of female infertility (5). Therefore, metformin may be beneficial before conception or during gestation in the following ways:

1. Fertility treatment of women with PCOS

PCOS is a common hormonal disorder (causing higher levels of male hormones) that negatively affects egg release from the ovary. Metformin alone or in combination with other medications can effectively induce ovulation, especially in non-obese women with PCOS. Additionally, metformin is considered useful in reducing the risk of ovarian hyperstimulation syndrome (painful swelling of the ovaries due to overstimulation) in women with PCOS undergoing in vitro fertilization (IVF) (6). Some studies also indicate that co-treatment with metformin may increase clinical pregnancy rates (7).

2. Treatment of gestational diabetes

Uncontrolled high blood glucose levels during pregnancy can negatively impact pregnancy. It may result in macrosomia, or a larger-sized baby, making a C-section necessary. The risk of miscarriage or stillbirths may also increase. Maternal complications may include high blood pressure, preeclampsia, and an increased risk of developing diabetes mellitus in the future (8). Though many doctors consider insulin the first-line treatment for gestational diabetes, current scientific evidence supports the safe use of metformin and dietary changes to control high blood sugar in pregnant women. Compared to insulin, metformin treatment has shown to cause less weight gain in pregnant women, and it is more patient compliant and cost-effective (4).

3. Treatment of pre-existing type 2 diabetes in pregnant women

Earlier, metformin was replaced with insulin when a woman with pre-existing type 2 diabetes got pregnant since doctors were unsure of its safety. However, several current studies show that metformin effectively controls hyperglycemia during pregnancy. Additionally, pregnant women receiving combination therapy of metformin and insulin require less insulin compared to insulin treatment alone (9).

What Is The Metformin Dosage In Pregnancy?

The dosage of metformin during pregnancy is best ascertained by your doctor based on your health requirements. However, metformin therapy for gestational diabetes usually begins with a dose of 500mg, which may be increased up to 2500mg, depending on how your body responds to it in terms of glycemic control and side effects (8).

Are There Side Effects Of Metformin?

The common side effects of metformin include (10) (11):

Some adverse effects that are rare but may have more severe outcomes are:

  • Hypoglycemia or a sudden fall in blood glucose levels.
  • Lactate build-up in the body, causing lactic acidosis. Pre-existing liver or kidney disorders increase its risk. Immediate medical attention is required in case of symptoms such as breathing troubles, shivering, fatigue, and muscle pain.
  • Decreased vitamin B12 levels in the body due to long-term use.

What Are The Alternatives To Metformin In Pregnancy?

The following therapeutic agents may be used in cases where it is inappropriate to use metformin during pregnancy (8).

  • The American Diabetes Association recommends insulin for treating gestational diabetes. It is the standard therapy for the condition when dietary changes and exercise are insufficient to manage elevated blood sugar levels.
  • Among oral antihyperglycemic agents, glyburide may be used in doses of 2.5mg to 20mg.

Frequently Asked Questions

1. Does metformin affect babies?

Metformin can cross the placenta and reach the growing fetus, but it has not been associated with the occurrence of congenital anomalies. Babies born to mothers on metformin may have a normal body weight and less risk of low blood sugar when compared to babies of insulin-treatment pregnancies (12).

2. Can metformin cause twin pregnancy?

Ovarian induction with combination therapy containing metformin as an agent may cause an increased incidence of twin or multiple pregnancies. However, further research is required to establish its prevalence (13).

3. Does metformin prevent miscarriage?

Metformin treatment may help reduce the prevalence of miscarriage in women with PCOS and diabetes (14) (15).

4. Does metformin cause weight loss in pregnancy?

No evidence suggests that metformin causes weight loss during pregnancy, but studies indicate that the medication may prevent weight gain in obese pregnant women (16).

Metformin is FDA-approved only for treating type 2 diabetes mellitus. Its use for PCOS and gestational diabetes are off-label. PCOS causes insulin resistance, resulting in hyperinsulinemia. However, metformin normalizes insulin levels, decreasing the luteinizing hormone and androgen levels to improve the menstrual cycle (10). Consuming metformin while pregnant can help effectively control gestational diabetes, and its benefits outweigh the risks. However, the decision to start metformin therapy should be taken by your doctor.

Key Pointers

  • Metformin is effective in controlling hyperglycemia and is considered safe during pregnancy.
  • It may be used with other drugs for inducing ovulation in women with PCOS.
  • Metformin therapy is not associated with any major congenital anomalies.

References:

MomJunction's articles are written after analyzing the research works of expert authors and institutions. Our references consist of resources established by authorities in their respective fields. You can learn more about the authenticity of the information we present in our editorial policy.
  1. Metformin Information.
    https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/metformin-information
  2. Metformin in pregnancy: study shows no safety concerns.
    https://www.gov.uk/drug-safety-update/metformin-in-pregnancy-study-shows-no-safety-concerns
  3. Nisha Nathan and Shannon D Sullivan; (2014); The utility of metformin therapy in reproductive-aged women with polycystic ovary syndrome (PCOS).
    https://pubmed.ncbi.nlm.nih.gov/24720592/
  4. Robert S. Lindsay and Mary R. Loeken; (2017); Metformin use in pregnancy: promises and uncertainties.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552827/
  5. PCOS (Polycystic Ovary Syndrome) and Diabetes.
    https://www.cdc.gov/diabetes/basics/pcos.html#
  6. Neil P. Johnson; (2014); Metformin use in women with polycystic ovary syndrome.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4200666/
  7. Hatem Abu Hashim; 2015; Twenty years of ovulation induction with metformin for PCOS; what is the best available evidence?
    https://pubmed.ncbi.nlm.nih.gov/26656973/
  8. Bryan S. Quintanilla Rodriguez and Heba Mahdy; (2021); Gestational Diabetes.
    https://www.ncbi.nlm.nih.gov/books/NBK545196/
  9. Thomas M. Polasek et al.; (2018); Metformin treatment of type 2 diabetes mellitus in pregnancy: update on safety and efficacy.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5971402/
  10. Calette Corcoran and Tibb F. Jacobs; (2021); Metformin.
    https://www.ncbi.nlm.nih.gov/books/NBK518983/
  11. Metformin.
    https://www.healthdirect.gov.au/metformin
  12. Taking metformin for gestational diabetes.
    medsafe.govt.nz/consumers/educational-material/MetforminforGestationalDiabetes.pdf
  13. Clare Boothroyd and Anusch Yazdani. Higher-order multiple pregnancy associated with metformin in women with polycystic ovary syndrome: two cases and review of the literature.
    https://pubmed.ncbi.nlm.nih.gov/16412759/
  14. Mawahib A S Al-Biate; (2015); Effect of metformin on early pregnancy loss in women with polycystic ovary syndrome.
    https://pubmed.ncbi.nlm.nih.gov/26166338/
  15. Steve Hyer et al.; (2018); Metformin in Pregnancy: Mechanisms and Clinical Applications.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073429/
  16. Valentina D’Ambrosio et al.; (2019); Metformin reduces maternal weight gain in obese pregnant women: A systematic review and meta-analysis of two randomized controlled trials.
    https://pubmed.ncbi.nlm.nih.gov/30945418/
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Dr. Joyani Das

Dr. Joyani Das is a PhD in Pharmacology with over two years of experience in academics. Previously, she worked as an associate professor, faculty of Pharmacology. With her research background in preclinical studies and a zeal for scientific writing, she joined MomJunction as a health writer. Her research work was published in international journals and publications, such as Elsevier, Current... more

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