TERIS
TERIS Agent
Updated: 03/2024

METFORMIN

Metformin is a biguanide antihyperglycemic agent that is used orally to treat non-insulin-dependent diabetes mellitus and polycystic ovary syndrome.
Magnitude of Teratogenic Risk to Child Born After Exposure During Gestation
UNLIKELY
Quality and Quantity of Data on Which Risk Estimate is Based
GOOD
Comments
1) THERAPEUTIC DOSES OF METFORMIN DURING PREGNANCY ARE UNLIKELY TO POSE A SUBSTANTIAL TERATOGENIC RISK, BUT THE DATA ARE INSUFFICIENT TO STATE THAT THERE IS NO RISK.

2) MANY WOMEN WHO TAKE METFORMIN DURING PREGNANCY HAVE DIABETES MELLITUS, WHICH ITSELF CAN ADVERSELY AFFECT EMBRYONIC AND FETAL DEVELOPMENT. INTERPRETATION OF AVAILABLE HUMAN DATA ON METFORMIN IS DIFFICULT BECAUSE OF THIS CONFOUNDING BY MATERNAL DIABETES.

Summary of Available Literature:

CONGENITAL ANOMALIES IN THE CHILDREN OF WOMEN WITH PREGESTATIONAL TYPE 2 DIABETES MELLITUS OR GESTATIONAL DIABETES

Studies of congenital anomalies in the children of diabetic women who took metformin early in pregnancy are confounded by the teratogenic effects of maternal diabetes. The risks of congenital anomalies estimated from such studies may be useful in counseling pregnant women with diabetes who are being treated with metformin but cannot be used to determine the teratogenic potential of metformin treatment in human pregnancy.

Associations were observed with maternal metformin treatment of diabetes during the first trimester of pregnancy among 3570 infants with cardiac septal defects (odds ratio=2.1, 95% confidence interval 1.0-4.4), 748 infants with anorectal defects (odds ratio=3.2, 95% confidence interval 1.1-8.9), 3454 infants with oral clefts (odds ratio=2.3, 95% confidence interval 1.2-4.6), 1134 infants with craniosynostosis (odds ratio=2.4, 95% confidence interval 1.0-6.0), and 882 infants with limb reduction defects (odds ratio=2.9, 95% confidence interval 1.1-7.7) in the National Birth Defects Prevention Study (Dukhovny et al., 2018). With the exception of craniosynostosis, all of these associations were seen more strongly with maternal insulin treatment for diabetes.

A higher overall frequency of major congenital anomalies was observed among 219 infants whose mothers took metformin for diabetes during the first trimester of pregnancy when compared to infants and fetuses whose mothers did not take any hypoglycemic agent (odds ratio=3.95, 95% confidence interval 1.77-9.41) in a European multicenter teratogen information service study (Panchaud et al., 2018). The risk for major congenital anomalies in this study increased with greater severity of maternal diabetes.

The rate of malformations was not significantly different between 2852 infants of women with type 2 diabetes treated with metformin alone in the first trimester of pregnancy and 878 infants born to disease-matched women treated with insulin alone in a Nordic registry-based cohort study (4.4 vs 5.7%) (Kjerpeseth et al., 2023). The adjusted risk of malformations did not appear to be increased for either metformin alone or metformin combined with insulin when compared to insulin alone. Likewise, no increase in risk of congenital anomalies or nonlive birth was found among 1577 women with type 2 diabetes treated with metformin in combination with insulin during the first trimester when compared to 850 diabetic women treated with insulin monotherapy in a United States observational cohort study (Chiu et al., 2024). 

In a retrospective cohort study of pregnancies in women with gestational diabetes, the frequency of congenital anomalies was not significantly increased among 186 infants and fetuses whose mothers were treated with metformin during the first trimester when compared to 151 infants and fetuses whose mothers were treated with insulin any time during pregnancy (Vanlalhruaii et al., 2018). The frequency of major congenital anomalies was similar among 90 infants whose mothers had been treated with metformin and 80 infants whose mothers had been treated with insulin for diabetes during the first trimester of pregnancy in an Israeli teratogen information service study (Diav-Citrin et al., 2018). The rate of major congenital anomalies was similar among the infants of 85 women with type 2 diabetes who had been treated with metformin during the first trimester of pregnancy and among the infants of 121 type 2 diabetic women who received other kinds of treatment or no treatment during the first trimester in another study (Hughes & Rowan, 2006).

In a meta-analysis of randomized controlled trials and cohort studies, first trimester treatment with metformin was not associated with a meaningful increase in the risk of major congenital anomalies among infants of 1122 women with pregestational diabetes (Abolhassani et al., 2023). 

CONGENITAL ANOMALIES IN THE CHILDREN OF WOMEN WITH POLYCYSTIC OVARY SYNDROME OR OBESITY (BUT NOT DIABETES)

Studies of congenital anomalies in the children of women who took metformin early in pregnancy for indications other than diabetes may be confounded by the metabolic correlates of maternal obesity, which is associated with polycystic ovary syndrome and insulin resistance. The risks of congenital anomalies estimated from such studies may be useful in counselling non-diabetic pregnant women who are being treated with metformin but may not reflect the teratogenic potential of metformin treatment in human pregnancy.

In the National Birth Defects Prevention Study, associations were observed with maternal metformin treatment of subfertility during the first trimester of pregnancy among 1692 infants with secundum atrial septal defects (odds ratio=2.0, 95% confidence interval 1.0-3.9) and 882 infants with limb reduction defects (odds ratio=3.3, 95% confidence interval 1.50-7.2) (Dukhovny et al., 2018). Similar associations were seen with maternal metformin or insulin treatment during the first trimester for diabetes in this study.

A meta-analysis of epidemiological studies conducted prior to 2014 concluded that the risk of congenital anomalies does not appear to be increased among the infants of women treated for polycystic ovary syndrome with metformin during the first trimester of pregnancy (Cassina et al., 2014). No recurrent pattern of congenital anomalies was apparent among the affected children. Similarly, in an updated meta-analysis of randomized controlled trials and cohort studies, first trimester treatment with metformin was not associated with a meaningful increase in the risk of major congenital anomalies among infants of 529 women with polycystic ovary syndrome (Abolhassani et al., 2023).

The frequencies of major congenital anomalies and of cardiac defects were no greater than expected among 173 infants or fetuses whose mothers took metformin during the first trimester of pregnancy for indications other than pregestational diabetes in a European multicenter teratogen information service study (Panchaud et al., 2018). In another teratogen information service study, the frequency of major congenital anomalies did not appear to be substantially increased among 45 infants whose mothers had been treated with metformin for polycystic ovary syndrome (Diav-Citrin et al., 2018).

The frequency of congenital anomalies was not increased among 209 and 202 infants, respectively, in two randomized controlled trials of metformin treatment of obese, non-diabetic women during the second and third trimesters of pregnancy (Chiswick et al., 2015; Syngelaki et al., 2016).

CONGENITAL ANOMALIES IN THE CHILDREN OF WOMEN EXPOSED TO METFORMIN DURING PREGNANCY FOR VARIOUS INDICATIONS

The risk of congenital anomalies was not increased among 315 infants whose mothers were treated with metformin for polycystic ovary syndrome, diabetes or insulin resistance during the first trimester of pregnancy in a German teratogen information service study (Scherneck et al., 2018). The malformations differed in each infant in the metformin-exposed group. In a Finnish registry study, the overall frequency of major congenital anomalies was not increased among 3697 infants born to women prescribed metformin during pregnancy for any indication when compared to infants of mothers treated with insulin (Brand et al., 2022).

A signal suggesting a possible association with maternal metformin treatment during the first trimester of pregnancy was reported among infants with pulmonary valve atresia in an intergroup analysis of 50,167 infants with various congenital anomalies who had been reported to one of 11 European congenital anomaly registries (Given et al., 2018). No comparison to infants without congenital anomalies was available in this study, and the signal could have arisen by chance.

NEURODEVELOPMENTAL OUTCOMES

None of 126 infants born to women who had been treated with metformin for polycystic ovary disease during at least the first trimester of pregnancy was noted to have developmental delay by 18 months of age (Glueck et al., 2004). No differences in neurodevelopmental test scores at 18 months or two years of age were observed between children born to mothers who were treated with metformin and those born to mothers who were treated with insulin for gestational diabetes (Ijas et al., 2015; Tertti et al., 2015; Wouldes et al., 2016).

Cognitive and neuropsychological outcomes at nine years of age were similar between 82 children of women treated with metformin during pregnancy and children born to women treated with insulin for gestational diabetes in a prospective Finnish study (Paavilainen et al., 2023). Similarly, long-term cognitive functioning was no different between 52 children whose mothers were treated with metformin during pregnancy and those who received placebo in a follow-up study of two randomized controlled trials (Greger et al., 2020). In a meta-analysis of controlled studies, no association was found between maternal treatment with metformin at any time during pregnancy and adverse neurodevelopmental outcomes in 7641 adolescents (Gordon et al., 2024).

ADVERSE PREGNANCY, NEONATAL AND OTHER CHILDHOOD OUTCOMES

The frequencies of neonatal hypoglycemia, macrosomia, perinatal mortality, prematurity, respiratory distress, hyperbilirubinemia, and neonatal intensive care unit admission in infants of diabetic mothers who are treated with metformin during pregnancy have usually been found to be lower or similar to those of infants whose diabetic mothers were treated with insulin (Balani et al., 2009; Ruholamin et al., 2014; Refuerzo et al., 2015; Diav-Citrin et al., 2018; Panchaud et al., 2018; Simeonova-Krstevska et al., 2018; Vanlalhruaii et al., 2018; Picon-Cesar et al., 2021; Sheng et al., 2023; Wu et al., 2024). Metformin treatment during early pregnancy may reduce the risk of spontaneous abortion, fetal growth restriction, and preterm delivery in women with polycystic ovary syndrome or other non-diabetic indications (Lautatzis et al., 2013; Al-Biate, 2015; Zeng et al., 2016; Elmaraezy et al., 2017; Hyer et al., 2018; Panchaud et al., 2018).

The frequency of small-for-gestational age birth was higher among infants whose mothers were treated with metformin during pregnancy, as compared to insulin, in a registry-based cohort study and a prospective, randomized controlled trial (Feig et al., 2020; Brand et al., 2022). Among women with polycystic ovary syndrome, metformin use during pregnancy has been associated with larger newborn head circumference but such increases were within the normal range (Cao et al., 2021; Nilsen et al., 2024).

Nine-year-old children whose mothers were treated with metformin during pregnancy in a randomized controlled trial of women with gestational diabetes had greater weights, arm and waist circumferences, waist-to-height ratios, triceps skinfold thickness, fat mass, lean mass, and abdominal fat volumes than the children of insulin-treated mothers (Rowan et al., 2018). Similar effects have also been seen in some follow-up studies, but not in others (Carlsen et al., 2012; Ro et al., 2012; Ijas et al., 2015; Tertti et al., 2016; Hanem et al., 2018; van Weelden et al., 2018). No differences in anthropometric measurements, including weight, height, and skinfold thicknesses, were found between two-year-old children of women with diabetes treated with metformin during pregnancy as compared to placebo-treated diabetic women in a follow-up study of a randomized controlled trial (Feig et al., 2023).

Cardiovascular risk was not increased among the children of 19 obese women treated with metformin during pregnancy when compared to children of obese, placebo-treated women in a follow-up study of a randomized controlled trial (Yang et al., 2022). Moreover, improved cardiovascular outcomes (lower central hemodynamic and cardiac diastolic indices) were observed in 77 children born to obese women treated with metformin during pregnancy when compared to children of obese, placebo-treated women in a randomized controlled trial (Panagiotopoulou et al., 2020). No difference in systolic or diastolic blood pressure was found between two-year-old children whose mothers were treated with metformin for gestational diabetes in the second or third trimester of pregnancy and children whose mothers were treated with insulin in a randomized clinical trial (Battin et al., 2015).

In a meta-analysis of randomized controlled trials and prospective randomized controlled studies that focused on longitudinal growth, infants of women treated with metformin for gestational diabetes had lower average birth weights when compared to infants of insulin-treated mothers but showed accelerations in postnatal growth such that children were heavier and had higher body mass index by mid-childhood (Tarry-Adkins et al., 2019).

ANIMAL TERATOLOGY STUDIES

Increased fetal death but no significant increase in malformations was observed when pregnant rats were treated with 10-20 times the maximum human therapeutic dose of metformin (Tuchmann-Duplessis & Mercier-Parot, 1961). Oral administration of metformin to pregnant rats at a dose that was 6 times the maximum therapeutic dose in humans did not alter the weight of the offspring at birth or in adulthood (Vidigal et al., 2018).

No adverse effects of maternal metformin exposure during pregnancy on offspring growth, cardiovascular, or metabolic outcomes were identified in a meta-analysis of controlled animal studies (van Hoorn et al., 2024).

References:

(Each paper is classified as a review [R], human case report [C], human epidemiological study [E], human clinical series [S], animal study [A], or other [O].)
Abolhassani N, Winterfeld U, Kaplan YC, Jaques C, Minder Wyssmann B, Del Giovane C, Panchaud A: Major malformations risk following early pregnancy exposure to metformin: a systematic review and meta-analysis. BMJ Open Diabetes Res Care 11(1):e002919, 2023. [R]
 
Al-Biate MAS: Effect of metformin on early pregnancy loss in women with polycystic ovary syndrome. Taiwan J Obstet Gynecol 54(3):266-269, 2015. [E]
 
Balani J, Hyer SL, Rodin DA, Shehata H: Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: a case-control study. Diabet Med 26(8):798-802, 2009. [E]
 
Battin MR, Obolonkin V, Rush E, Hague W, Coat S, Rowan J: Blood pressure measurement at two years in offspring of women randomized to a trial of metformin for GDM: follow up data from the MiG trial. BMC Pediatr 15:54, 2015. [E]
 
Brand KMG, Saarelainen L, Sonajalg J, Boutmy E, Foch C, Vaarasmaki M, Morin-Papunen L, Schlachter J; CLUE Study Group; Hakkarainen KM, Korhonen P: Metformin in pregnancy and risk of adverse long-term outcomes: a register-based cohort study. BMJ Open Diabetes Res Care 10(1):e002363, 2022. [E]
 
Cao Q, Hu Y, Fu J, Huang X, Wu L, Zhang J, Huang W: Gestational metformin administration in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized control studies. J Obstet Gynaecol Res 47(12):4148-4157, 2021. [R]
 
Carlsen SM, Martinussen MP, Vanky E: Metformin's effect on first-year weight gain: a follow-up study. Pediatrics 130(5):e1222-e1226, 2012. [E]
 
Cassina M, Dona M, Di Gianantonio E, Litta P, Clementi M: First-trimester exposure to metformin and risk of birth defects: a systematic review and meta-analysis. Hum Reprod Update 20(5):656-669, 2014. [R]
 
Chiswick C, Reynolds RM, Denison F, Drake AJ, Forbes S, Newby DE, Walker BR, Quenby S, Wray S, Weeks A, Lashen H, Rodriguez A, Murray G, Whyte S, Norman JE: Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 3(10):778-786, 2015. [E]

Chiu Y-H, Huybrechts KF, Patorno E, Yland JJ, Cesta CE, Bateman BT, Seely EW, Hernan MA, Hernandez-Diaz S: Metformin use in the first trimester of pregnancy and risk for nonlive birth and congenital malformations: emulating a target trial using real-world data. Ann Intern Med 177(7):862-870, 2024. [E]
 
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 80:85-91, 2018. [E]
 
Dukhovny S, Van Bennekom CM, Gagnon DR, Hernandez Diaz S, Parker SE, Anderka M, Werler MM, Mitchell AA: Metformin in the first trimester and risks for specific birth defects in the National Birth Defects Prevention Study. Birth Defects Res 110(7):579-586, 2018. [E]
 
Elmaraezy A, Abushouk AI, Emara A, Elshahat O, Ahmed H, Mostafa MI: Effect of metformin on maternal and neonatal outcomes in pregnant obese non-diabetic women: a meta-analysis. Int J Reprod Biomed (Yazd) 15(8):461-470, 2017. [R]
 
Feig DS, Donovan LE, Zinman B, Sanchez JJ, Asztalos E, Ryan EA, Fantus IG, Hutton E, Armson AB, Lipscombe LL, Simmons D, Barrett JFR, Karanicolas PJ, Tobin S, McIntyre HD, Tian SY, Tomlinson G, Murphy KE: Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 8(10):834-844, 2020. [E]
 
Feig DS, Sanchez JJ, Murphy KE, Asztalos E, Zinman B, Simmons D, Haqq AM, Fantus IG, Lipscombe L, Armson A, Barrett J, Donovan L, Karanicolas P, Tobin S, Mangoff K, Klein G, Jiang Y, Tomlinson G, Hamilton J: Outcomes in children of women with type 2 diabetes exposed to metformin versus placebo during pregnancy (MiTy Kids): a 24-month follow-up of the MiTy randomised controlled trial. Lancet Diabetes Endocrinol 11(3):191-120, 2023. [E]
 
Given JE, Loane M, Garne E, Addor M-C, Bakker M, Bertaut-Nativel B, Gatt M, Klungsoyr K, Lelong N, Morgan M, Neville AJ, Pierini A, Rissmann A, Dolk H: Metformin exposure in first trimester of pregnancy and risk of all or specific congenital anomalies: exploratory case-control study. BMJ 361:k2477, 2018. [E]
 
Glueck CJ, Goldenberg N, Pranikoff J, Loftspring M, Sieve L, Wang P: Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. Hum Reprod 19(6):1323-1330, 2004. [E]
 
Gordon HG, Atkinson JA, Tong S, Mehdipour P, Cluver C, Walker SP, Lindquist AC, Hastie RM: Metformin in pregnancy and childhood neurodevelopmental outcomes: a systematic review and meta-analysis. Am J Obstet Gynecol 2024 Mar 7 (published online ahead of print). [R]
 
Greger HK, Hanem LGE, Ostgard HF, Vanky E: Cognitive function in metformin exposed children, born to mothers with PCOS--follow-up of an RCT. BMC Pediatr 20(1):60, 2020. [E]
 
Hanem LGE, Stridsklev S, Juliusson PB, Salvesen O, Roelants M, Carlsen SM, Odegsrd R, Vanky E: Metformin use in PCOS pregnancies increases the risk of offspring overweight at 4 years of age: Follow-up of two RCTs [published response appears in J Clin Endocrinol Metab 103(9):3521, 2018]. J Clin Endocrinol Metab 103(4):1612-1621, 2018. [E]
 
Hughes RCE, Rowan JA: Pregnancy in women with Type 2 diabetes: who takes metformin and what is the outcome? Diabet Med 23(3):318-322, 2006. [E]
 
Hyer S, Balani J, Shehata H: Metformin in pregnancy: mechanisms and clinical applications. Int J Mol Sci 19(7):E1954, 2018. [R]
 
Ijas H, Vaarasmaki M, Saarela T, Keravuo R, Raudaskoski T: A follow-up of a randomised study of metformin and insulin in gestational diabetes mellitus: growth and development of the children at the age of 18 months. BJOG 122(7):994-1000, 2015. [E]
 
Kjerpeseth LJ, Cesta CE, Furu K, Engeland A, Gissler M, Gulseth HL, Karlstad O, Leinonen MK, Pazzagli L, Zoega H, Cohen JM: Metformin versus insulin and risk of major congenital malformations in pregnancies with type 2 diabetes: a Nordic register-based cohort study. Diabetes Care 46(8):1556-1564, 2023. [E]
 
Lautatzis ME, Goulis DG, Vrontakis M: Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: a systematic review. Metabolism 62(11):1522-1534, 2013. [R]
 
Nilsen GO, Simpson MR, Hanem LGE, Lovvik TS, Odegard R, Stokkeland LMT, Andersen MS, Juliusson PB, Vanky E: Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero. Acta Obstet Gynecol Scand 103(1):176-187, 2024. [E]
 
Paavilainen E, Nyman A, Niinikoski H, Nikkinen H, Veijola R, Vaarasmaki M, Tossavainen P, Ronnemaa T, Tertti K: Metformin versus insulin for gestational diabetes: cognitive and neuropsychological profiles of children aged 9 years. J Dev Behav Pediatr 44(9):e642-e650, 2023. [E]
 
Panagiotopoulou O, Syngelaki A, Georgiopoulos G, Simpson J, Akolekar R, Shehata H, Nicolaides K, Charakida M: Metformin use in obese mothers is associated with improved cardiovascular profile in the offspring. Am J Obstet Gynecol 223(2):246.e1-246.e10, 2020. [E]
 
Panchaud A, Rousson V, Vial T, Bernard N, Baud D, Amar E, De Santis M, Pistelli A, Dautriche A, Beau-Salinas F, Cassina M, Dunstan H, Passier A, Kaplan YC, Duman MK, Manakova E, Eleftheriou G, Klinger G, Winterfeld U, Rothuizen LE, Buclin T, Csajka C, Hernandez-Diaz S: Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services. Br J Clin Pharmacol 84(3):568-578, 2018. [E]
 
Picon-Cesar MJ, Molina-Vega M, Suarez-Arana M, Gonzalez-Mesa E, Sola-Moyano AP, Roldan-Lapez R, Romero-Narbona F, Olveira G, Tinahones FJ, Gonzalez-Romero S: Metformin for gestational diabetes study: metformin vs insulin in gestational diabetes: glycemic control and obstetrical and perinatal outcomes: randomized prospective trial. Am J Obstet Gynecol 225(5):517.e1-517.e17, 2021. [E]
 
Refuerzo JS, Gowen R, Pedroza C, Hutchinson M, Blackwell SC, Ramin S: A pilot randomized, controlled trial of metformin versus insulin in women with type 2 diabetes mellitus during pregnancy. Am J Perinatol 30(2):163-170, 2015. [E]
 
Ro TB, Ludvigsen HV, Carlsen SM, Vanky E: Growth, body composition and metabolic profile of 8-year-old children exposed to metformin in utero. Scand J Clin Lab Invest 72(7):570-575, 2012. [E]
 
Rowan JA, Rush EC, Plank LD, Lu J, Obolonkin V, Coat S, Hague WM: Metformin in gestational diabetes: the offspring follow-up (MiG TOFU): body composition and metabolic outcomes at 7-9 years of age. BMJ Open Diabetes Res Care 6(1):e000456, 2018. [E]
 
Ruholamin S, Eshaghian S, Allame Z: Neonatal outcomes in women with gestational diabetes mellitus treated with metformin in compare with insulin: a randomized clinical trial. J Res Med Sci 19(10):970-975, 2014. [E]
 
Scherneck S, Schlinke N, Beck E, Grupe K, Weber-Schoendorfer C, Schaefer C: Pregnancy outcome after first-trimester exposure to metformin: a prospective cohort study. Reprod Toxicol 81:79-83, 2018. [E]
 
Sheng B, Ni J, Lv B, Jiang G, Lin X, Li H: Short-term neonatal outcomes in women with gestational diabetes treated using metformin versus insulin: a systematic review and meta-analysis of randomized controlled trials. Acta Diabetol 60(5):595-608, 2023. [R]
 
Simeonova-Krstevska S, Bogoev M, Bogoeva K, Zisovska E, Samardziski I, Velkoska-Nakova V, Livrinova V, Todorovska I, Sima A, Blazevska-Siljanoska V: Maternal and neonatal outcomes in pregnant women with gestational diabetes mellitus treated with diet, metformin or insulin. Open Access Maced J Med Sci 6(5):803-807, 2018. [E]
 
Syngelaki A, Nicolaides KH, Balani J, Hyer S, Akolekar R, Kotecha R, Pastides A, Shehata H: Metformin versus placebo in obese pregnant women without diabetes mellitus. N Engl J Med 374(5):434-443, 2016. [E]
 
Tarry-Adkins JL, Aiken CE, Ozanne SE: Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis. PLoS Med 16(8):e1002848, 2019. [R]
 
Tertti K, Eskola E, Ronnemaa T, Haataja L: Neurodevelopment of two-year-old children exposed to metformin and insulin in gestational diabetes mellitus. J Dev Behav Pediatr 36(9):752-757, 2015. [E]
 
Tertti K, Toppari J, Virtanen HE, Sadov S, Ronnemaa T: Metformin treatment does not affect testicular size in offspring born to mothers with gestational diabetes. Rev Diabet Stud 13(1):59-65, 2016. [E]
 
Tuchmann-Duplessis H, Mercier-Parot I: [Repercussions of a hypoglycemic drug, N-N-dimethylbiguanide HCl, on gestation and fetal development in rats.] C R Hebd Seances Acad Sci 253:321-323, 1961. [A]
 
van Hoorn EGM, Rademaker D, van der Wel AWT, DeVries JH, Franx A, van Rijn BB, Kooy A, Siegelaar SE, Roseboom TJ, Ozanne SE, Hooijmans CR, Painter RC: Fetal and post-natal outcomes in offspring after intrauterine metformin exposure: A systematic review and meta-analysis of animal experiments. Diabet Med 41(2):e15243, 2024. [R] & [A]
 
van Weelden W, Wekker V, de Wit L, Limpens J, Ijas H, van Wassenaer-Leemhuis AG, Roseboom TJ, van Rijn BB, DeVries JH, Painter RC: Long-term effects of oral antidiabetic drugs during pregnancy on offspring: a systematic review and meta-analysis of follow-up studies of RCTs. Diabetes Ther 9(5):1811-1829, 2018. [R]
 
Vanlalhruaii, Dasgupta R, Ramachandran R, Mathews JE, Regi A, Thomas N, Gupta V, Visalakshi P, Asha HS, Paul T, Thomas N: How safe is metformin when initiated in early pregnancy? A retrospective 5-year study of pregnant women with gestational diabetes mellitus from India. Diabetes Res Clin Pract 137:47-55, 2018. [E]
 
Vidigal CB, Novi DRBS, Moura KF, Picinin R, Montagnini BG, da Silva RdeNO, da Silva MDV, de Andrade FG, Akamine EH, Gerardin DCC, Ceravolo GS: Intrauterine exposure to metformin: Evaluation of endothelial and perivascular adipose tissue function in abdominal aorta of adult offspring. Life Sci 207:72-79, 2018. [A]
 
Wouldes TA, Battin M, Coat S, Rush EC, Hague WM, Rowan JA: Neurodevelopmental outcome at 2 years in offspring of women randomised to metformin or insulin treatment for gestational diabetes. Arch Dis Child Fetal Neonatal Ed 101(6):F488-F493, 2016. [E]
 
Wu R, Zhang Q, Li Z: A meta-analysis of metformin and insulin on maternal outcome and neonatal outcome in patients with gestational diabetes mellitus. J Matern Fetal Neonatal Med 37(1):2295809, 2024. [R]
 
Yang L, Lacey L, Whyte S, Quenby S, Denison FC, Dhaun N, Norman JE, Drake AJ, Reynolds RM: Metformin in obese pregnancy has no adverse effects on cardiovascular risk in early childhood. J Dev Orig Health Dis 13(3):390-394, 2022. [E]
 
Zeng X-L, Zhang Y-F, Tian Q, Xue Y, An R-F: Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome: A meta-analysis. Medicine 95(36):e4526, 2016. [R]
Agent Metadata
TERIS Agent Number: 2322
Bibliographic Search Date: 03/2024
CAS: 1115-70-4, 657-24-9
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Metformin (9085)