» Articles » PMID: 37798604

Efficacy and Safety of Metformin During Pregnancy: an Update

Abstract

During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the offspring. Metformin has been validated for maternal efficacy and safety, achieving comparable glycemic control with insulin. Additionally, it reduces maternal weight gain and possibly the occurrence of hypertensive disorders. During the early neonatal period, metformin administration does not increase the risk of congenital anomalies or other major adverse effects, including lower APGAR score at 5 min, neonatal intensive care unit admissions, and respiratory distress syndrome. Several studies have demonstrated a reduction in neonatal hypoglycemia. Metformin has been associated with an increase in preterm births and lower birth weight, although this effect is controversial and depends on the indication for which it was administered. Evidence indicates possible altered fetal programming and predisposition to childhood obesity and metabolic syndrome during adulthood after use of metformin in pregnancy. With critical questions still requiring a final verdict, ongoing research on the field must be conducted.

Citing Articles

NLRP3 inflammasomes pathway: a key target for Metformin.

Hosseini Y, Niknejad A, Sabbagh Kashani A, Gholami M, Roustaie M, Mohammadi M Inflammopharmacology. 2025; .

PMID: 40042723 DOI: 10.1007/s10787-025-01702-4.


The Role of Placental MFF-Mediated Mitochondrial Fission in Gestational Diabetes Mellitus.

Wei L, Fang C, Jiang Y, Zhang H, Gao P, Zhou X Diabetes Metab Syndr Obes. 2025; 18:541-554.

PMID: 39995822 PMC: 11849531. DOI: 10.2147/DMSO.S484002.


Metformin for Treating Gestational Diabetes: What Have We Learned During the Last Two Decades? A Systematic Review.

Gerede A, Domali E, Chatzakis C, Margioula-Siarkou C, Petousis S, Stavros S Life (Basel). 2025; 15(1).

PMID: 39860070 PMC: 11766790. DOI: 10.3390/life15010130.


Plasma Glycated CD59 and Gestational Diabetes Mellitus: A Systematic Review.

Asadi Z, Safari-Faramani R, Aghaz F, Vaisi-Raygani A, Jalilian S Endocrinol Diabetes Metab. 2024; 7(6):e70013.

PMID: 39548720 PMC: 11568234. DOI: 10.1002/edm2.70013.


Gestational Diabetes: An Update 60 Years After O'Sullivan and Mahan.

McIntyre H, Kampmann U, Clausen T, Laurie J, Ma R J Clin Endocrinol Metab. 2024; 110(1):e19-e31.

PMID: 39389786 PMC: 11651698. DOI: 10.1210/clinem/dgae709.


References
1.
Feig D, Donovan L, Zinman B, Sanchez J, Asztalos E, Ryan E . Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2020; 8(10):834-844. DOI: 10.1016/S2213-8587(20)30310-7. View

2.
Niromanesh S, Alavi A, Sharbaf F, Amjadi N, Moosavi S, Akbari S . Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Diabetes Res Clin Pract. 2012; 98(3):422-9. DOI: 10.1016/j.diabres.2012.09.031. View

3.
Anness A, Baldo A, Webb D, Khalil A, Robinson T, Mousa H . Effect of metformin on biomarkers of placental- mediated disease: A systematic review and meta-analysis. Placenta. 2021; 107:51-58. DOI: 10.1016/j.placenta.2021.02.021. View

4.
Diav-Citrin O, Steinmetz-Shoob S, Shechtman S, Ornoy A . In-utero exposure to metformin for type 2 diabetes or polycystic ovary syndrome: A prospective comparative observational study. Reprod Toxicol. 2018; 80:85-91. DOI: 10.1016/j.reprotox.2018.05.007. View

5.
De Leo V, Musacchio M, Piomboni P, di Sabatino A, Morgante G . The administration of metformin during pregnancy reduces polycystic ovary syndrome related gestational complications. Eur J Obstet Gynecol Reprod Biol. 2011; 157(1):63-6. DOI: 10.1016/j.ejogrb.2011.03.024. View