Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: a systematic review
Abstract
Background Metformin is an effective oral anti-hyperglycemic agent that is widely used to manage diabetes mellitus type 2 in the general population and more recently, in pregnancy. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus.Objective (i) To provide background for the use of metformin during pregnancy through a narrative review and (ii) to critically appraise the published evidence on the efficacy and safety of using metformin during pregnancy through a systematic review.Results Metformin appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight or obese women. However, patients with multiple risk factors for insulin resistance may not meet their treatment goals with metformin alone and may require supplementary insulin. Evidence suggests that there are potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. Furthermore, patients are more accepting of metformin than insulin. The use of metformin throughout pregnancy in women with polycystic ovary syndrome reduces the rates of early pregnancy loss and preterm labor and protects against fetal growth restriction. There have been no demonstrable teratogenic effects, intra-uterine deaths or developmental delays with the use of metformin.Conclusions The publications reviewed in this paper support the efficacy and safety of metformin during pregnancy with respect to immediate pregnancy outcomes. Because there are no guidelines for the continuous use of metformin in pregnancy, the duration of treatment is based on clinical judgment and experience on a case-by-case basis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Rare side-effects such as mild erythema and decreased vitamin B12 absorption have been associated with long-term administration of metformin.
“In addition, rare side-effects such as mild erythema and decreased vitamin B12 absorption have been associated with long-term administration(252).”
From Metformin, the Aspirin of the 21st Century: Its Role in Gestational Diabetes Mellitus, Prevention of Preeclampsia and Cancer, and the Promotion of Longevity (2017) · cites this paper as [252]
Cites
Effect of In Utero and Early-Life Conditions on Adult Health and Disease
Gluckman, P. D., Hanson, M. A., Cooper, C., & Thornburg, K. L. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0708473 · Cited by 3,898 · see citing works
Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes
Crowther, C. A., Hiller, J. E., Moss, J. R., McPhee, A. J., Jeffries, W. S., & Robinson, J. S. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa042973 · Cited by 3,159 · see citing works
Bailey, C. J., & Turner, R. C. (1996) · New England Journal of Medicine · doi:10.1056/nejm199602293340906 · Cited by 1,726 · see citing works
Metformin versus insulin for the treatment of gestational diabetes
Rowan, J. A., Hague, W. M., Gao, W., Battin, M. R., & Moore, M. P. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0707193 · Cited by 1,291 · see citing works
Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E. (1995) · New England Journal of Medicine · doi:10.1056/nejm199508313330903 · Cited by 1,148 · see citing works
Krentz, A. J., & Bailey, C. J. (2005) · Drugs · doi:10.2165/00003495-200565030-00005 · Cited by 1,132 · see citing works
Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome
Legro, R. S., Barnhart, H. X., Schlaff, W. D., Carr, B. R., Diamond, M. P., Carson, S. A., Steinkampf, M. P., Coutifaris, C., McGovern, P. G., Cataldo, N. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa063971 · Cited by 1,027 · see citing works
Thomas, N., Senthil, K., & Kapoor, N. (2016) · Jaypee Brothers Medical Publishers (P) Ltd. eBooks · doi:10.5005/jp/books/12651_7 · Cited by 943 · see citing works
Velazquez, E. M., Mendoza, S., Hamer, T., Sosa, F., & Glueck, C. J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90209-7 · Cited by 865 · see citing works
Nestler, J. E., Jakubowicz, D. J., Evans, W. S., & Pasquali, R. (1998) · New England Journal of Medicine · doi:10.1056/nejm199806253382603 · Cited by 781 · see citing works
Clausen, T. D., Mathiesen, E. R., Hansen, T., Pedersen, O., Jensen, D. M., Lauenborg, J., & Damm, P. (2008) · Diabetes Care · doi:10.2337/dc07-1596 · Cited by 724 · see citing works
Gestational diabetes: The consequences of not treating
Langer, O., Yogev, Y., Most, O., & Xenakis, E. M. J. (2005) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2004.11.039 · Cited by 677 · see citing works
Moghetti, P., Castello, R., Negri, C., Tosi, F., Perrone, F., Caputo, M., Zanolin, E., & Muggeo, M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.1.6293 · Cited by 660 · see citing works
Silverman, B. L., Metzger, B. E., Cho, N. H., & Loeb, C. A. (1995) · Diabetes Care · doi:10.2337/diacare.18.5.611 · Cited by 643 · see citing works
Bailey, C. J. (1992) · Diabetes Care · doi:10.2337/diacare.15.6.755 · Cited by 593 · see citing works
Effects of metformin on early pregnancy loss in the polycystic ovary syndrome
Jakubowicz, D., Iuorno, M., Jakubowicz, S., Roberts, K. A., Nestler, J., & Fabbri, A. (2002) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jcem.87.2.8207 · Cited by 539 · see citing works
Palomba, S., Falbo, A., Zullo, F., & Orio, F. (2009) · Endocrine Reviews · doi:10.1210/er.2008-0030 · Cited by 426 · see citing works
Mechanism of metformin action in obese and lean noninsulin-dependent diabetic subjects
DEFRONZO, R. A., BARZILAI, N., & SIMONSON, D. C. (1991) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-73-6-1294 · Cited by 408 · see citing works
Lactic Acidosis in Patients with Diabetes Treated with Metformin
Misbin, R. I., Green, L., Stadel, B. V., Gueriguian, J. L., Gubbi, A., & Fleming, G. A. (1998) · New England Journal of Medicine · doi:10.1056/nejm199801223380415 · Cited by 403 · see citing works
Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin
Glueck, C. J., Wang, P., Goldenberg, N., & Sieve-Smith, L. (2002) · Human Reproduction · doi:10.1093/humrep/17.11.2858 · Cited by 384 · see citing works
Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU)
Rowan, J. A., Rush, E. C., Obolonkin, V., Battin, M., Wouldes, T., & Hague, W. M. (2011) · Diabetes Care · doi:10.2337/dc11-0660 · Cited by 379 · see citing works
Moghetti, P. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.85.1.139 · Cited by 342 · see citing works
Tang, T., Glanville, J., Hayden, C. J., White, D., Barth, J. H., & Balen, A. H. (2006) · Human Reproduction · doi:10.1093/humrep/dei311 · Cited by 335 · see citing works
Glueck, C. J., Wang, P., Kobayashi, S., Phillips, H., & Sieve-Smith, L. (2002) · Fertility and Sterility · doi:10.1016/s0015-0282(01)03202-2 · Cited by 325 · see citing works
Vanky, E., Stridsklev, S., Heimstad, R., Romundstad, P., Skogøy, K., Kleggetveit, O., Hjelle, S., von Brandis, P., Eikeland, T., Flo, K., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-0853 · Cited by 315 · see citing works
Metformin for the treatment of the polycystic ovary syndrome
Nestler, J. E. (2008) · New England Journal of Medicine · doi:10.1056/nejmct0707092 · Cited by 313 · see citing works
Effect of Metformin on Carbohydrate and Lipoprotein Metabolism in NIDDM Patients
Wu, M. ‐., Johnston, P., Sheu, W. H., Hollenbeck, C. B., Jeng, C., Goldfine, I. D., Chen, Y. D., & Reaven, G. M. (1990) · Diabetes Care · doi:10.2337/diacare.13.1.1 · Cited by 257 · see citing works
Glueck, C. J. (2004) · Human Reproduction · doi:10.1093/humrep/deh263 · Cited by 251 · see citing works
Diamanti‐Kandarakis, E., Christakou, C. D., Kandaraki, E., & Economou, F. (2009) · European Journal of Endocrinology · doi:10.1530/eje-09-0733 · Cited by 246 · see citing works
Placental passage of metformin in women with polycystic ovary syndrome
Vanky, E., Zahlsen, K., Spigset, O., & Carlsen, S. M. (2005) · Fertility and Sterility · doi:10.1016/j.fertnstert.2004.11.051 · Cited by 245 · see citing works
Morin-Papunen, L., Rantala, A. S., Unkila-Kallio, L., Tiitinen, A., Hippeläinen, M., Perheentupa, A., Tinkanen, H., Bloigu, R., Puukka, K., Ruokonen, A., et al. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-3061 · Cited by 243 · see citing works
Vanky, E., Salvesen, K., Heimstad, R., Fougner, K., Romundstad, P., & Carlsen, S. (2004) · Human Reproduction · doi:10.1093/humrep/deh347 · Cited by 242 · see citing works
Glueck, C. J., Wang, P., Fontaine, R. N., Tracy, T., & Sieve-Smith, L. (1999) · Metabolism · doi:10.1016/s0026-0495(99)90113-0 · Cited by 228 · see citing works
Ijäs, H., Vääräsmäki, M., Morin-Papunen, L. C., Keravuo, R., Ebeling, T., Saarela, T., & Raudaskoski, T. (2010) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2010.02763.x · Cited by 215 · see citing works
Population pharmacokinetics of metformin in late pregnancy
Charles, B., Norris, R., Xiao, X., & Hague, W. (2006) · Therapeutic Drug Monitoring · doi:10.1097/01.ftd.0000184161.52573.0e · Cited by 212 · see citing works
Niromanesh, S., Alavi, A., Sharbaf, F. R., Amjadi, N., Moosavi, S., & Akbari, S. (2012) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2012.09.031 · Cited by 202 · see citing works
Mechanism of metformin action in non-insulin-dependent diabetes
Jackson, R. A., Hawa, M. I., Jaspan, J. B., Sim, B. M., DiSilvio, L., Featherbe, D., & Kurtz, A. B. (1987) · Diabetes · doi:10.2337/diab.36.5.632 · Cited by 202 · see citing works
A Risk-Benefit Assessment of Metformin in Type 2 Diabetes Mellitus
Howlett, H. C. S., & Bailey, C. J. (1999) · Drug Safety · doi:10.2165/00002018-199920060-00003 · Cited by 199 · see citing works
The role of metformin in polycystic ovary syndrome: a systematic review
Moll, E., van der Veen, F., & van Wely, M. (2007) · Human Reproduction Update · doi:10.1093/humupd/dmm026 · Cited by 188 · see citing works
Randomized trial of metformin vs insulin in the management of gestational diabetes
Spaulonci, C. P., Bernardes, L. S., Trindade, T. C., Zugaib, M., & Francisco, R. P. V. (2013) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2013.03.022 · Cited by 183 · see citing works
Contraindications to the use of metformin
Jones, G. C., Macklin, J. P., & Alexander, W. D. (2003) · BMJ · doi:10.1136/bmj.326.7379.4 · Cited by 149 · see citing works
Dhulkotia, J. S., Ola, B., Fraser, R., & Farrell, T. (2010) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2010.06.044 · Cited by 145 · see citing works
Balani, J., Hyer, S. L., Rodin, D. A., & Shehata, H. A. (2009) · Diabetic Medicine · doi:10.1111/j.1464-5491.2009.02780.x · Cited by 145 · see citing works
Tulppala, M., Stenman, U., Cacciatore, B., & Ylikorkala, O. (1993) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1993.tb12978.x · Cited by 144 · see citing works
Bjercke, S., Dale, P. O., Tanbo, T. G., Storeng, R., Ertzeid, G., & Åbyholm, T. (2002) · Gynecologic and Obstetric Investigation · doi:10.1159/000067719 · Cited by 138 · see citing works
Effect of metformin on glucose metabolism in the splanchnic bed
Bailey, C. J., Wilcock, C., & Day, C. (1992) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1992.tb09093.x · Cited by 130 · see citing works
Impaired Glucose Tolerance in Pregnant Women With Polycystic Ovary Syndrome
RADON, P. A., MCMAHON, M. J., & MEYER, W. R. (1999) · Obstetrics and Gynecology · doi:10.1016/s0029-7844(99)00252-5 · Cited by 123 · see citing works
Effects of Metformin on Early Pregnancy Loss in the Polycystic Ovary Syndrome
Jakubowicz, D. J. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.87.2.524 · Cited by 122 · see citing works
Gestational Diabetes: Incidence, Maternal Characteristics, and Perinatal Outcome
Sepe, S. J., Connell, F. A., Geiss, L. S., & Teutsch, S. M. (1985) · Diabetes · doi:10.2337/diab.34.2.s13 · Cited by 117 · see citing works
Bailey, C. J. (1993) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(93)90411-p · Cited by 111 · see citing works
Inhibition of hepatic gluconeogenesis by metformin
Wollen, N., & Bailey, C. J. (1988) · Biochemical Pharmacology · doi:10.1016/0006-2952(88)90617-x · Cited by 109 · see citing works
Metformin in polycystic ovary syndrome
Diamanti‐Kandarakis, E., Economou, F., Palimeri, S., & Christakou, C. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05679.x · Cited by 109 · see citing works
Gabbe, S. G. (1986) · New England Journal of Medicine · doi:10.1056/nejm198610163151609 · Cited by 108 · see citing works
Metformin for gestational diabetes in routine clinical practice
Goh, J. E. L., Sadler, L. C., & Rowan, J. (2011) · Diabetic Medicine · doi:10.1111/j.1464-5491.2011.03361.x · Cited by 98 · see citing works
Metformin reduces abortion in pregnant women with polycystic ovary syndrome
Khattab, S., Mohsen, I. A., Foutouh, I. A., Ramadan, A. R., Moaz, M., & Al-Inany, H. G. (2006) · Gynecological Endocrinology · doi:10.1080/09513590601010508 · Cited by 98 · see citing works
Tertti, K., Ekblad, U., Vahlberg, T. J., & Rönnemaa, T. (2008) · The Review of Diabetic Studies · doi:10.1900/rds.2008.5.95 · Cited by 94 · see citing works
Ekpebegh, C. O., Coetzee, E. J., van der Merwe, L., & Levitt, N. S. (2007) · Diabetic Medicine · doi:10.1111/j.1464-5491.2007.02053.x · Cited by 92 · see citing works
Nawaz, F. H., Khalid, R., Naru, T. Y., & Rizvi, J. (2008) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2008.00856.x · Cited by 91 · see citing works
Leo, V. D., Musacchio, M. C., Piomboni, P., Sabatino, A. D., & Morgante, G. (2011) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2011.03.024 · Cited by 89 · see citing works
Prevention of gestational diabetes by metformin plus diet in patients with polycystic ovary syndrome
Glueck, C. J., Pranikoff, J., Aregawi, D., & Wang, P. (2007) · Fertility and Sterility · doi:10.1016/j.fertnstert.2007.03.036 · Cited by 81 · see citing works
Begum, M. R., Khanam, N. N., Quadir, E., Ferdous, J., Begum, M. S., Khan, F. I., & Begum, A. (2008) · Journal of obstetrics and gynaecology research · doi:10.1111/j.1447-0756.2008.00876.x · Cited by 70 · see citing works
Metformin in the treatment of infertility in polycystic ovarian syndrome: an alternative perspective
Nestler, J. E. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.04.073 · Cited by 69 · see citing works
Bailey, C. J., & Nattrass, M. (1988) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(88)80043-0 · Cited by 68 · see citing works
Contraindications to use of metformin
ELDER, A. T. (2003) · BMJ · doi:10.1136/bmj.326.7392.762/a · Cited by 60 · see citing works
Gandhi, P., Bustani, R., Madhuvrata, P., & Farrell, T. J. (2011) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2011.11.018 · Cited by 56 · see citing works
Effect of pregnancy on the pharmacokinetics of metformin
Hughes, R. C. E., Gardiner, S. J., Begg, E. J., & Zhang, M. (2005) · Diabetic Medicine · doi:10.1111/j.1464-5491.2005.01769.x · Cited by 54 · see citing works
Metformin use and diabetic pregnancy—has its time come?
Hawthorne, G. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01856.x · Cited by 52 · see citing works
Bolton, S., Cleary, B., Walsh, J., Dempsey, E., & Turner, M. J. (2009) · European Journal of Pediatrics · doi:10.1007/s00431-008-0737-7 · Cited by 45 · see citing works
Nawaz, F. H., & Rizvi, J. (2009) · Gynecologic and Obstetric Investigation · doi:10.1159/000268051 · Cited by 43 · see citing works
Glueck, C. J., Goldenberg, N., Pranikoff, J., Khan, Z., Padda, J., & Wang, P. (2012) · Current Medical Research and Opinion · doi:10.1185/03007995.2012.755121 · Cited by 41 · see citing works
Oral hypoglycemic agents for gestational diabetes mellitus?
Maymone, A. C., Baillargeon, J., Ménard, J., & Ardilouze, J. (2011) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2011.521740 · Cited by 40 · see citing works
Neonatal outcome in polycystic ovarian syndrome patients treated with metformin during pregnancy
Kovo, M., Weissman, A., Gur, D., Levran, D., Rotmensch, S., & Glezerman, M. (2006) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767050600682370 · Cited by 37 · see citing works
Effects of metformin use in pregnant patients with polycystic ovary syndrome
Kumar, P., & Khan, K. (2012) · Journal of Human Reproductive Sciences · doi:10.4103/0974-1208.101012 · Cited by 33 · see citing works
Vanky, E., de Zegher, F., Díaz, M., Ibáñez, L., & Carlsen, S. M. (2012) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.12015 · Cited by 33 · see citing works
Metformin treatment for Type 2 diabetes in pregnancy?
Simmons, D. S. (2010) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2010.05.002 · Cited by 29 · see citing works
Metformin: a multitasking medication
Bailey, C. J. (2008) · Diabetes and Vascular Disease Research · doi:10.3132/dvdr.2008.026 · Cited by 21 · see citing works
Efficacy of Metformin in Non-Insulin-Dependent Diabetes Mellitus
Gueriguian, J. L., Green, L., Misbin, R. I., Stadel, B. V., & Fleming, G. A. (1996) · New England Journal of Medicine · doi:10.1056/nejm199601253340414 · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pregnancy complications in women with polycystic ovary syndrome
Palomba, S., de Wilde, M. A., Falbo, A., Koster, M. P. H., La Sala, G. B., & Fauser, B. C. J. M. (2015) · Human Reproduction Update · doi:10.1093/humupd/dmv029 · Cited by 691 · see citing works
Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome
Wang, J., Wu, D., Guo, H., & Li, M. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.116940 · Cited by 322 · see citing works
(2014) · PubMed Central · Cited by 280 · see citing works
Romero, R., Erez, O., Hüttemann, M., Maymon, E., Panaitescu, B., Conde-Agudelo, A., Pacora, P., Yoon, B. H., & Grossman, L. I. (2017) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.06.003 · Cited by 253 · see citing works
Nandi, A. A., Chen, Z., Patel, R., & Poretsky, L. (2014) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2013.10.003 · Cited by 189 · see citing works
Cassina, M., Donà, M., Di Gianantonio, E., Litta, P., & Clementi, M. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu022 · Cited by 143 · see citing works
Sivalingam, V. N., Myers, J., Nicholas, S., Balen, A. H., & Crosbie, E. J. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu037 · Cited by 107 · see citing works
Metformin and metabolic diseases: a focus on hepatic aspects
Zheng, J., Woo, S., Hu, X., Botchlett, R. E., Chen, L., Huo, Y., & Wu, C. (2015) · Frontiers of Medicine · doi:10.1007/s11684-015-0384-0 · Cited by 99 · see citing works
Metabolic Health, Insulin, and Breast Cancer: Why Oncologists Should Care About Insulin
Yee, L. D., Mortimer, J. E., Natarajan, R. D., Dietze, E. C., & Seewaldt, V. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00058 · Cited by 91 · see citing works
Hauspurg, A. K., Sutton, E. F., Catov, J. M., & Caritis, S. N. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11196 · Cited by 83 · see citing works
Gestational diabetes mellitus: Where are we now?
Ashwal, E., & Hod, M. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.01.021 · Cited by 80 · see citing works
Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome
Zeng, X., Zhang, Y., Tian, Q., Xue, Y., & An, R. (2016) · Medicine · doi:10.1097/md.0000000000004526 · Cited by 78 · see citing works
Shpakov, A. O. (2021) · Pharmaceuticals · doi:10.3390/ph14010042 · Cited by 81 · see citing works
Hastie, R. M., Brownfoot, F., Pritchard, N., Hannan, N. J., Cannon, P., Nguyen, V., Palmer, K. R., Beard, S., Tong, S., & Kaitu’u‐Lino, T. J. (2019) · Hypertension · doi:10.1161/hypertensionaha.118.12300 · Cited by 71 · see citing works
Feng, Y., & Yang, H. (2017) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2016.1228061 · Cited by 68 · see citing works
Novel Interventions for the Prevention of Preeclampsia
Ma’ayeh, M., Rood, K. M., Kniss, D. A., & Costantine, M. M. (2020) · Current Hypertension Reports · doi:10.1007/s11906-020-1026-8 · Cited by 62 · see citing works
Liang, H., Ma, S., Xiao, Y., & Tan, H.-Z. (2017) · Medicine · doi:10.1097/md.0000000000007939 · Cited by 55 · see citing works
Impact of metformin on reproductive tissues: an overview from gametogenesis to gestation.
Bertoldo, M. J., Faure, M., Dupont, J., & Froment, P. (2014) · PubMed Central · doi:10.3978/j.issn.2305-5839.2014.06.04 · Cited by 56 · see citing works
Gestational Diabetes Mellitus:current knowledge and unmet needs
Koning, S. H., Hoogenberg, K., Lutgers, H. L., van den Berg, P. P., & Wolffenbuttel, B. H. R. (2016) · Journal of Diabetes · doi:10.1111/1753-0407.12422 · Cited by 51 · see citing works
Tan, X., Li, S., Chang, Y., Fang, C., Liu, H., Zhang, X., & Wang, Y. (2016) · Clinical and Investigative Medicine · doi:10.25011/cim.v39i4.27091 · Cited by 51 · see citing works
The use of oral hypoglycaemic agents in pregnancy
Holt, R. I. G., & Lambert, K. (2013) · Diabetic Medicine · doi:10.1111/dme.12376 · Cited by 51 · see citing works
Cluver, C. A., Walker, S. P., Mol, B. W., Hall, D. R., Hiscock, R. J., Brownfoot, F., Kaitu’u‐Lino, T. J., & Tong, S. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-025809 · Cited by 48 · see citing works
Gestational diabetes mellitus: Multi-disciplinary treatment approaches
Kintiraki, E., & Goulis, D. G. (2018) · Metabolism · doi:10.1016/j.metabol.2018.03.025 · Cited by 46 · see citing works
Self-citationEndoplasmic Reticulum Stress Is Increased in Adipose Tissue of Women with Gestational Diabetes
Liong, S., & Lappas, M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122633 · Cited by 44 · see citing works
The emerging role of metformin in gestational diabetes mellitus
Gray, S. G., McGuire, T. M., Cohen, N., & Little, P. J. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12893 · Cited by 40 · see citing works
Metformin: new applications for an old drug
Naseri, A., Sanaie, S., Hamzehzadeh, S., Sahebari, S. S., Hosseini, M., Gholipour-khalili, E., Rezazadeh-Gavgani, E., Majidazar, R., Seraji, P., Daneshvar, S., et al. (2022) · Journal of Basic and Clinical Physiology and Pharmacology · doi:10.1515/jbcpp-2022-0252 · Cited by 39 · see citing works
Pregestational Diabetes in Pregnancy
Sugrue, R. P., & Zera, C. (2018) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/j.ogc.2018.01.002 · Cited by 38 · see citing works
Gestational diabetes: An overview with attention for developing countries
Schiavone, M., Putoto, G., Laterza, F., & Pizzol, D. (2016) · Endocrine Regulations · doi:10.1515/enr-2016-0010 · Cited by 36 · see citing works
Alternative Interventions to Prevent Oxidative Damage following Ischemia/Reperfusion
Rodríguez-Lara, S. Q., Cardona-Muñóz, E. G., Ramírez-Lizardo, E. J., Totsuka-Sutto, S. E., Castillo‐Romero, A., García-Cobián, T. A., & García‐Benavides, L. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/7190943 · Cited by 32 · see citing works
Tan, M. H., Alquraini, H., Mizokami‐Stout, K., & MacEachern, M. (2016) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2016.06.008 · Cited by 32 · see citing works
Ansari, R. M. (2016) · Journal of Chinese Integrative Medicine · doi:10.1016/s2095-4964(16)60240-6 · Cited by 30 · see citing works
Valdés, E., Sepúlveda-Martínez, Á., Paula Candia, P., Abusada, N., Orellana, R., Manukian, B., & Cuellar, E. (2017) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.13477 · Cited by 30 · see citing works
Comments on gestational diabetes mellitus: from pathophysiology to clinical practice
Poulakos, P., Mintziori, G., Tsirou, E., Taousani, E., Savvaki, D., Harizopoulou, V. C., & Goulis, D. G. (2015) · HORMONES · doi:10.14310/horm.2002.1570 · Cited by 31 · see citing works
Self-citationLorca, R. A., Matarazzo, C. J., Bales, E. S., Houck, J. A., Orlicky, D. J., Euser, A. G., Julian, C. G., & MOORE, L. G. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00644.2019 · Cited by 27 · see citing works
Hu, S., Xu, B., Long, R., & Jin, L. (2020) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/1471-0528.16557 · Cited by 28 · see citing works
Unresolved controversies in gestational diabetes
Barbour, L. A. (2014) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000080 · Cited by 27 · see citing works
Metformin in gestational diabetes: An emerging contender
Singh, A. K., & Singh, R. (2015) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.149317 · Cited by 26 · see citing works
Rojas, J., Chávez-Castillo, M., & Bermúdez, V. (2014) · International Journal of Reproductive Medicine · doi:10.1155/2014/797681 · Cited by 26 · see citing works
D’Ambrosio, V., Brunelli, R., Vena, F., Mascio, D. D., Marchetti, C., Boccherini, C., Piccioni, M. G., Panici, P. B., & Giancotti, A. (2019) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3164 · Cited by 24 · see citing works
Effects of hypoxia on uteroplacental and fetoplacental vascular function during pregnancy
Arenas, G. A., & Lorca, R. A. (2024) · Frontiers in Physiology · doi:10.3389/fphys.2024.1490154 · Cited by 23 · see citing works
Placental dysfunction in obese women and antenatal surveillance strategies
Jeve, Y. B., Konje, J. C., & Doshani, A. (2014) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2014.09.007 · Cited by 23 · see citing works
Cwynar-Zając, Ł. (2021) · Pediatric Endocrinology Diabetes and Metabolism · doi:10.5114/pedm.2021.107166 · Cited by 22 · see citing works
Evidence-Based Management of Infertility in Women With Polycystic Ovary Syndrome
Bergh, C., Moore, M., & Gundell, C. (2015) · Journal of Obstetric, Gynecologic & Neonatal Nursing · doi:10.1016/j.jogn.2015.10.001 · Cited by 20 · see citing works
Metformin treatment of type 2 diabetes mellitus in pregnancy: update on safety and efficacy
Polasek, T. M., Doogue, M. P., & Thynne, T. (2018) · Therapeutic Advances in Drug Safety · doi:10.1177/2042098618769831 · Cited by 20 · see citing works
Musa, O. A. H., Syed, A., Mohamed, A. M., Chivese, T., Clark, J. M., Furuya‐Kanamori, L., Xu, C., Toft, E. S., Bashir, M., Abou‐Samra, A., et al. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105546 · Cited by 19 · see citing works
Wang, M., Li, S., Wang, F., Zou, J., & Zhang, Y. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.8863 · Cited by 18 · see citing works
Jones, V., Dietze, E. C., Jovanović‐Talisman, T., McCune, J. S., & Seewaldt, V. L. (2020) · Frontiers in Public Health · doi:10.3389/fpubh.2020.509714 · Cited by 19 · see citing works
Vanlalhruaii, Dasgupta, R., Ramachandran, R., Mathews, J. E., Regi, A., Thomas, N., Gupta, V., Visalakshi, P., Asha, H. S., Paul, T. V., et al. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.01.002 · Cited by 17 · see citing works
Using metformin in the presence of renal disease
Chowdhury, T. A., Wright, R., & Yaqoob, M. (2015) · BMJ · doi:10.1136/bmj.h1758 · Cited by 17 · see citing works
Mousa, A., Løvvik, T. S., Nikkinen, H., Carlsen, S. M., Morin-Papunen, L. C., Tertti, K., Rönnemaa, T., Syngelaki, A., Nicolaides, K. H., Shehata, H. A., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-036981 · Cited by 16 · see citing works
Hendrick, V. C., Dasher, R., Gitlin, M. J., & Parsi, M. (2017) · Annals of Clinical Psychiatry · doi:10.1177/104012371702900205 · Cited by 15 · see citing works
Diagnostic biomolecules and combination therapy for pre-eclampsia
Qi, J., Wu, B., Chen, X., Wei, W., & Yao, X. (2022) · Reproductive Biology and Endocrinology · doi:10.1186/s12958-022-01003-3 · Cited by 17 · see citing works
Longer-term outcomes in offspring of GDM mothers treated with metformin versus insulin
Zhen, X. M., Li, X., & Chen, C. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.07.002 · Cited by 16 · see citing works
Metformin for the management of gestational diabetes mellitus
Singh, K. P., Rahimpanah, F., & Barclay, M. (2015) · Australian and New Zealand Journal of Obstetrics and Gynaecology · doi:10.1111/ajo.12311 · Cited by 14 · see citing works
Management of diabetes and pregnancy – When to start and what pharmacological agent to choose?
Hiersch, L., & Yogev, Y. (2014) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2014.04.020 · Cited by 14 · see citing works
Drugs to Control Diabetes During Pregnancy
Feghali, M. N., Umans, J. G., & Catalano, P. M. (2019) · Clinics in Perinatology · doi:10.1016/j.clp.2019.02.005 · Cited by 13 · see citing works
New Insight into Metformin Mechanism of Action and Clinical Application
Yan, Y., Kover, K. L., & Moore, W. V. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.91148 · Cited by 12 · see citing works
MOORE, L. G., Lorca, R. A., Gumina, D. L., Wesolowski, S. R., Reisz, J. A., Cioffi‐Ragan, D., Houck, J. A., Banerji, S., Euser, A. G., D’Alessandro, A., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00193.2024 · Cited by 11 · see citing works
Zhen, X. M., Li, X., & Chen, C. (2018) · Obesity Medicine · doi:10.1016/j.obmed.2018.08.001 · Cited by 10 · see citing works
Puscheck, E. E., Bolnick, A. D., Awonuga, A. O., Yang, Y., Abdulhasan, M. A., Li, Q., Secor, E. R., Louden, E. D., Hüttemann, M., & Rappolee, D. A. (2018) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-018-1213-6 · Cited by 10 · see citing works
Wildschut, H. I. J., Duvekot, J. J., Cook, J. R., Bacchus, L. J., Bewley, S., Creighton, S. M., Dear, J., Williams, D., Kilby, M. D., Crouch, N. S., et al. (2017) · Cambridge University Press eBooks · doi:10.1017/9781108349185 · Cited by 10 · see citing works
Jung, M.-L., Renke, T., Nowak, O., Jauckus, J., Zorn, M., Capp, E., Strowitzki, T., & Germeyer, A. (2015) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-015-3650-0 · Cited by 9 · see citing works
Gestational diabetes: an onomastic opportunity
Kalra, S., Baruah, M. P., Gupta, Y., & Kalra, B. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70104-9 · Cited by 8 · see citing works
Huang, C.-F., Tiao, M., Lin, I.-C., Huang, L., Sheen, J., Tain, Y., Hsu, C., Tsai, C., Lin, Y., & Yu, H. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232214239 · Cited by 8 · see citing works
Gestational Diabetes and Risk for Childhood Obesity: Mini Review
Chen, J. G. J. (2014) · Journal of Pregnancy and Child Health · doi:10.4172/2376-127x.1000e103 · Cited by 7 · see citing works
Diabetes Management beyond Pregnancy
Song, G., Wang, C., & Yang, H.-X. (2017) · Chinese Medical Journal · doi:10.4103/0366-6999.204938 · Cited by 7 · see citing works
Zeng, W., Luo, Y., Ou, J., Gan, D., Huang, M., Tomlinson, B., & Jiang, Y. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1654372 · Cited by 5 · see citing works
Metformin Exposure and Risk of Hypertensive Disorders of Pregnancy in Patients with Type 2 Diabetes
Racine, J. L., Adams, J. H., Antony, K. M., Hoppe, K. K., Iruretagoyena, J. I., Stewart, K. S., Eddy, A., & Rhoades, J. S. (2021) · American Journal of Perinatology · doi:10.1055/s-0041-1728821 · Cited by 5 · see citing works
Reply to Yanagisawa: Treatment of Pulmonary Lymphangioleiomyomatosis during Pregnancy
Gupta, N., Johnson, S. R., Moss, J., & McCormack, F. X. (2018) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201801-0043le · Cited by 5 · see citing works
Ben-Hander, G. M., Abdusalam, A. A. A., Saad, B., Makahleh, A., & Salhimi, S. M. (2019) · Chemical Science International Journal · doi:10.9734/csji/2019/v26i130081 · Cited by 4 · see citing works
Stewart, Z. A., & Murphy, H. R. (2014) · Medicine · doi:10.1016/j.mpmed.2014.10.010 · Cited by 3 · see citing works
Romeo, P., D’Anna, R., & Corrado, F. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13185387 · Cited by 3 · see citing works
AMPK function in uterine vasculature and placenta at high altitude
Lorca, R. A. (2025) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2024.0174 · Cited by 3 · see citing works
CME: Metformin – Dos und Don’ts CME-Fragen
Slahor, L. (2021) · Praxis · doi:10.1024/1661-8157/a003774 · Cited by 3 · see citing works
Metformina y diabetes gestacional
Martín-Herrasti, J. M. S., Alcázar-Álvarez, L. S., Serrano-Berrones, M. Á., Tirado-Chávez, J., & Castro-Herrera, G. A. (2014) · Redalyc (Universidad Autónoma del Estado de México) · Cited by 3 · see citing works
Stracquadanio, M., & Ciotta, L. (2015) · Springer eBooks · doi:10.1007/978-3-319-16760-2_6 · Cited by 3 · see citing works
MOORE, L. G., Wesolowski, S. R., Lorca, R. A., & Julian, C. G. (2025) · Acta Physiologica · doi:10.1111/apha.70093 · Cited by 2 · see citing works
Arshadi, M., Lotfi, M. H., Madadizadeh, F., Javaheri, A., & Soodejani, M. T. (2025) · Reproductive Health · doi:10.1186/s12978-025-02180-1 · Cited by 3 · see citing works
The Effect of Metformin in Preventing of Superimposed Preeclampsia: a Randomized Clinical Trial
Ahmadi, S., Salarifar, E., Ahmadi, K., Rahimi, M., & Bahraini, M. (2022) · Journal of Obstetrics Gynecology and Cancer Research · doi:10.30699/jogcr.7.5.399 · Cited by 2 · see citing works
Jakiel, G., Bijok, J., & Bińkowska, M. (2014) · Ginekologia Polska · doi:10.17772/gp/1765 · Cited by 2 · see citing works
Maternal and fetal insulin levels at birth in women with PCOS
Pasquali, R. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.61 · Cited by 2 · see citing works
Efectos perinatales de la metformina en diabetes gestacional
Lopez-Reyes, A., Escobedo-Aguirre, F., Lugo-Cruz, M. P., Jaén-Vento, L. A., & Macías‐Amezcua, M. D. (2020) · Clínica e Investigación en Ginecología y Obstetricia · doi:10.1016/j.gine.2020.09.002 · Cited by 3 · see citing works
Metformina y gliburida en el tratamiento de la diabetes gestacional
de Santander, M. I. X. N. D. M. U. I., Hernández, A. A., Castillo, D. R., & de Santander, U. I. (2015) · Revista Médicas UIS · doi:10.18273/revmed.v28n3-2015008 · Cited by 1 · see citing works
Oral Anti-diabetic Agents as an Alternative Treatment of Diabetes in Pregnancy
Laila, T. R. (2016) · American Journal of Clinical and Experimental Medicine · doi:10.11648/j.ajcem.20160402.11
Could metformin be used as a treatment for preeclampsia: A pilot study
Abdel‐Aleem, H., Shaamash, A. H., El-Azeem, H. G. A., Makhlouf, A., & Shaaban, O. M. (2018) · Journal of Current Medical Research and Practice · doi:10.4103/jcmrp.jcmrp_45_17 · Cited by 1 · see citing works
Martina, M., Chilova, R., Сокова, Е. А., Maslov, S., Poznyak, M. V., & Sevastyanov, G. (2024) · Vrach · doi:10.29296/25877305-2024-05-11 · Cited by 1 · see citing works
Mashaal, A., El-Yamany, H. Y., & Mansour, H. A. E. (2024) · Journal of Medicinal Food · doi:10.1089/jmf.2024.0021 · Cited by 1 · see citing works
Palomba, S., & Fauser, B. C. J. M. (2018) · Springer eBooks · doi:10.1007/978-3-319-45534-1_22 · Cited by 1 · see citing works
Pregestational Diabetes Mellitus
Norwitz, E. R., Saade, G. R., Miller, H. S., & Davidson, C. M. (2016) · Wiley eBooks · doi:10.1002/9781118849897.ch13 · Cited by 1 · see citing works
Balestrini, F. F., Anselmo Palacios, T., Juan Colán, P., & Eduardo Arias, R. (2014) · Revista de Obstetricia y Ginecología de Venezuela
Guía de práctica clínica de síndrome de ovario
Castillo, D., Tirado, F. J. G., Ortega, M., Castro, A. J., Tirado, D. C., & Ana, R. (2014) · Dialnet (Universidad de la Rioja)
Hernández, A. A., & Castillo, D. R. (2015)
Síndrome de ovario poliquístico e infertilidad: Opciones de tratamiento
Quintero, M., & Egleet, M. (2015) · Revista de Obstetricia y Ginecología de Venezuela
ГИПОГЛИКЕМИЧЕСКАЯ АКТИВНОСТЬ ГИПОЛИПИДЕМИЧЕСКИХ ПРЕПАРАТОВ
Titov, V. N. (2014) · CyberLeninK (CyberLeninka)
Review Article Oral Anti-diabetic Agents as an Alternative Treatment of Diabetes in Pregnancy
Laila, T. R., & Ahmed, S. S. (2016)
Balestrini, F. F. (2016) · Revista Venezolana de Endocrinología y Metabolismo
Zarif, N. Ö., Nicholson, E., & Cummings, M. (2016) · Practical Diabetes · doi:10.1002/pdi.2054
Abbas, A. M. (2018) · The Journal of Obstetrics and Gynecology of India · doi:10.1007/s13224-018-1121-9
Antidiabetic properties of centella asiatica in type II diabetic rats.
Oyenihi, A. B. (2016) · ResearchSpace (University of KwaZulu-Natal)
Treatment of Gestational Diabetes
Maged, A. M. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.86988
- Authors
- Lautatzis, M.-E., Goulis, D. G., & Vrontakis, M.
- Affiliations
- Aristotle University of Thessaloniki (GR)
- University of Manitoba (CA)
- Corresponding author
- Lautatzis, Maria-Elena
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 62
- Issue
- 11
- Pages
- 1522-1534
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W1979876574
- Cited by
- 113
- References
- 77
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 9 · 2022: 4 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 13 · 2017: 9 · 2016: 14 · 2015: 14 · 2014: 18 · 2013: 2
- FWCI
- 2.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- metformin, pregnancy, gestational diabetes mellitus, polycystic ovary syndrome, drug safety, teratogenicity, fetal growth restriction, preterm labor, miscarriage, gestational weight gain, neonatal outcomes, insulin resistance, insulin therapy comparison, maternal-fetal drug transfer
- MeSH terms
- Adult, Clinical Trials as Topic, Female, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Metformin, Obesity, Polycystic Ovary Syndrome, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Diabetes, Gestational, Treatment Outcome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
