Metformin In Pregnant Women Research Articles

Myoinositol and Metformin in the Prevention of Gestational Diabetes in High-Risk Patients: A Narrative Review.

Our hypothesis is that myoinositol and metformin in pregnant women with high-risk factors for glucose intolerance would reduce insulin resistance and consequently lower the incidence of gestational diabetes mellitus (GDM), a metabolic disorder of pregnancy characterized by maternal hyperglycemia due to deficient response to physiological insulin resistance, which may have a negative impact on perinatal outcome and long-term sequelae. In recent years, this pathology has become increasingly important given the global obesity epidemic and the delay in becoming pregnant, especially in industrialized countries. For this reason, the attempt to prevent, rather than cure, gestational diabetes is particularly important. In addition to lifestyle changes (especially diet and doing more exercise), myoinositol and metformin are the most promising factors at the moment, although not all RCTs published so far agree on their real effectiveness. A review of the articles published so far allows us to assume, albeit with some distinctions, that they can play a positive role.

Analysis of efficacy of metformin in pregnant women with Polycystic Ovarian Syndrome (PCOS).

Objective: (1)To analyze of efficacy of metformin in pregnant women with POCS regarding occurrence of gestational diabetes mellitus (2) To analyze parity distribution for efficacy of metformin regarding occurrence of gestational diabetes mellitus in pregnant women with POCS. Study Design: Descriptive Cases Series. Setting: Sheikh Zaid Hospital, Lahore. Period: July 1, 2019 to December 31, 2019. Methods: Till delivery 200 pregnant ladies were followed up to see if they developed GDM or not. A pre-prepared form was used to record metformin efficacy frequency and GDM in pregnant ladies with PCOS. For efficacy and parity (qualitative variables), percentages and frequencies were got calculated using SPSS.16. Results: Thirty two (16%) women got ‘0’ parity. Forty four (22%) got ‘1’parity. Fifty (25%) got ‘2’ parity. Forty two (21%) got ‘3’parity.While thirty two women (16%) got ‘4’ parity. Twenty two (78.57%) was efficacy for nulliparous patients. Thirty three (76.74%) was efficacy for primiparous patients. One hundred nine (84.50%) was efficacy for multiparous patients. Insignificant difference was noted as p was more than 0.05. In one hundred sixty six (83%) women metformin efficacy got achieved. Conclusion: Multiparous patients with PCOS showed relatively more efficacy (84.50%) of metformin against gestational diabetes mellitus while twenty five percent pregnant women with PCOS with a thorough use of metformin delivered two live neonates.

Anthropometrics of neonates born to mothers with PCOS with metformin or placebo exposure in utero.

Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre-pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z-scores. Linear regression models were used to estimate the effect of metformin on offspring z-scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S-testosterone, s-androstenedione, and s-sex-hormone binding globulin from four timepoints in pregnancy were analyzed. Compared with the PCOS-placebo group, newborns in the PCOS-metformin group had larger head circumference (head circumference z-score: mean difference = 0.25, 95% CI = 0.11- 0.40). This effect of metformin on head circumference z-score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS-phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS-placebo group were shorter than in the reference population (birth length z-score: mean = -0.04, 95% CI = -0.05 to -0.03), but head circumference and birthweight were similar. Larger head circumference was observed at birth in metformin-exposed offspring of mothers with PCOS. PCOS-offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight-to-height ratio at birth.

Prophylactic administration of metformin reduces gestational diabetes mellitus incidence in the high-risk populations: a meta-analysis : Metformin for gestational diabetes prevention.

Metformin exerts a good efficacy for gestational diabetes mellitus (GDM) treatment by regulating gluconeogenesis and insulin resistance, while no consensus about its preventive effect on GDM is reached yet. Thus, this meta-analysis aimed to comprehensively investigate the prophylactic administration of metformin in pregnant women at high risk of GDM. Databases (EMBASE, PubMed, Cochrane, CNKI, Wanfang, CQVIP) were searched to screen papers concerning the GDM prevention using metformin in women at high risk of GDM (polycystic ovary syndrome (PCOS), obese, and pregestational insulin resistance patients) until January 2023. Our study showed that five cohort studies and fifteen randomized controlled trials (RCTs) involving 3911 women were included. Pooled analysis showed that prophylactic metformin treatment (vs. control treatment) greatly reduced GDM rate (relative risk (RR) = 0.59, 95% confidence intervals (CI): 0.43-0.80). Subgroup analyses also revealed that prophylactic metformin treatment (vs. control treatment) decreased the GDM rate in the following patients' types: (1) in Asians (RR = 0.31, 95% CI: 0.23-0.41), (2) in PCOS patients (RR = 0.42, 95% CI: 0.26-0.68), and (3) in patients receiving high dose of metformin (mean dose > 1000mg) (RR = 0.59, 95% CI: 0.42-0.83). Concerning the quality of involved studies, the overall risk of bias was low. Egger's test implied that no publication bias existed in the findings. Moreover, sensitivity analysis suggested the pleasing robustness of the results. In conclusion, prophylactic metformin reduces GDM incidence in high-risk pregnant women, indicating its early-application benefits.

Efficacy of Prophylactic Use of Metformin in Prevention of Gestational Diabetes Mellitus in Nondiabetic Obese Pregnant Women

Background & Objective: Maternal obesity can increases pregnancy consequences like postpartum hemorrhage, preeclampsia, need for cesarean section, neonatal death, and fetal macrosomia. In this study, the efficacy of prophylactic use of metformin to prevent gestational diabetes mellitus in nondiabetic pregnant women with obesity was examined.Materials & Methods: This study was a clinical trial. Totally, 340 pregnant women who were in the first trimester were referred to the gynecology clinic of Motahhari hospital in Urmia after ensuring the absence of underlying diseases such as diabetes, hypertension, kidney, liver, and cardiovascular disease, without a history of allergy to metformin, in case of a singleton pregnancy, and Body Mass Index (BMI) above 30 were allocated to two equal groups. The intervention group was given 1000 mg of metformin, and the control group was given a placebo. Demographic information, including age, gravity, parity, live birth, birth, and maternal weight, previous delivery method, abortion, delivery method with its cause, polyhydramnios, NICU hospitalization, gestational age, mortality, and neonatal anomalies was also recorded. The results were analyzed using SPSS version 26.Results: In the control group, 15 mothers (9.4%) out of 160 people, and in the intervention group, 13 mothers (8.1%) had gestational diabetes (P < /i>=0.692). In the intervention group, the mean insulin dose was 10.8 ±3 units; in the control group, the mean insulin dose was 21.2±15.7 units (P=0.048). Twenty patients (6.7%) out of 297 obese patients and 8 patients (34.8%) in the morbid obesity group had diabetes (P < /i><0.001). In the control group, the mean weight of mothers was 8.04±2.5 kg; in the intervention group, it was 5.2±2.3 kg during pregnancy (P < /i><0.001). Gestational diabetes, delivery method, death one week after birth, preterm birth, polyhydramnios, and intensive care unit were similar in the two groups. Conclusion: Metformin in pregnant women with a BMI>30 deals with low maternal weight, reduced birth weight, and reduced insulin dose in diabetic mothers.

Efficacy and safety of metformin in pregnant women with polycystic ovary syndrome: a systematic review with meta-analysis of randomized and non-randomized controlled trials

Objective To evaluate the efficacy and safety of using metformin in pregnant women with polycystic ovarian syndrome (PCOS) and to explore the most effective and safe protocol by using a meta-analysis method. Methods Medline, EMBASE, Cochrane Library, and other databases were searched for randomized controlled trials and prospective cohort studies enrolling pregnant women with PCOS on receiving metformin or placebo or nothing. Subgroup analyses were undertaken. Results A total of 17 studies involving 2899 patients were included. Compared with control group, the use of metformin significantly reduced the incidence of preterm delivery (cumulative rate 3.86% vs 9.19%, relative risk (RR), 0.42 [95% confidence interval (CI), 0.25–0.71,]; p = .001), early miscarriage (cumulative rate 6.58% vs 18.35%, RR, 0.40 [95% CI, 0.20–0.78]; p = .007), gestational diabetes (cumulative rate 12.86% vs 22.91%, RR, 0.48 [95% CI, 0.26–0.89]; p = .02), and pre-eclampsia (cumulative rate 4.95% vs 7.72%, RR, 0.61 [95% CI, 0.40–0.93]; p = .02), the need for insulin treatment throughout pregnancy (cumulative rate 2.14% vs 5.12%, RR, 0.43 [95% CI, 0.22–0.85]; p = .01), and weight gain of pregnant women (mean difference, −2.45, [95% CI, −3.04 to −1.85]; p < .00001). Conclusions The use of metformin in pregnant women with PCOS can significantly reduce maternal complications. No significant difference was observed in serious maternal adverse events. The efficacy and safety of metformin are worthy of recognition.

Protein Interaction Network for Identifying Vascular Response of Metformin (Oral Antidiabetic)

Metformin is the most used oral anti-diabetic drug in the world and consequently is commonly found in the aquatic environment. Some studies demonstrated that metformin may act as an endocrine-disrupting-chemical (EDC) in fish, although it does not have a classic EDC structure. In this sense, the aim of this work was to evaluate the potential disrupting effect of metformin in the cardiovascular system through in vitro, ex vivo, and in silico studies. For this purpose, human umbilical artery (HUA) and rat aorta artery (RAA) were used. The toxic concentrations of metformin were determined by a cytotoxicity assay and in silico simulations were performed to analyze the interactions of metformin with hormonal receptors. Our results show that metformin decreases viability of the smooth muscle cells. Moreover, metformin induces a vasorelaxant effect in rat aorta and human models by an endothelium-dependent and -independent pathways. Furthermore, docking simulations showed that metformin binds to androgen receptors (AR) and estrogen receptors (ERα and ERβ). In conclusion, the in silico assays suggested that metformin has the potential to be an endocrine disruptor, acting mainly on ERα. Further studies are needed to use metformin in pregnant women without impairing the cardiovascular health of the future generation.

Abstract #806594: Safety of Metformin in Pregnant Women with Gestational Diabetes Mellitus

Abstract #806594: Safety of Metformin in Pregnant Women with Gestational Diabetes Mellitus

Factors Associated with the Need for Insulin as a Complementary Treatment to Metformin in Gestational Diabetes Mellitus.

To evaluate the factors associated with the need for insulin as a complementary treatment to metformin in pregnant women with gestational diabetes mellitus (GDM). A case-control study was performed from April 2011 to February 2016 with pregnant women with GDM who needed complementary treatments besides diet and physical exercise. Those treated with metformin were compared with those who, in addition to metformin, also needed the combination with insulin. Maternal characteristics and glycemic control were evaluated. Multinomial logistic regression models were developed to evaluate the influence of different therapies on neonatal outcomes. A total of 475 pregnant women who needed pharmacological therapy were evaluated. Of these, 366 (77.05%) were submitted to single therapy with metformin, and 109 (22.94%) needed insulin as a complementary treatment. In the analysis of the odds ratio (OR), fasting glucose (FG) < 90 mg/dL reduced the odds of needing the combination (OR: 0.438 [0.235-0.815]; p = 0.009], as well as primiparity (OR: 0.280 [0.111-0.704]; p = 0.007]. In obese pregnant women, an increased chance of needing the combination was observed (OR: 2,072 [1,063-4,039]; p = 0,032). Obesity resulted in an increased chance of the mother needing insulin as a complementary treatment to metformin, while FG < 90 mg/dL and primiparity were protective factors.

Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes

Metformin for women who are overweight or obese during pregnancy for improving maternal and infant outcomes

Real-World Experience of Adding Metformin in Pregnant Women with Type 1 Diabetes in a Chinese Population: A Retrospective Cohort.

IntroductionGlycemic control in pregnant women with type 1 diabetes (T1D) is challenging with only insulin, and the incidence rate of adverse perinatal outcomes is high. Increasing data have indicated the safety and effect of metformin in pregnancy; however, no relevant data are available in pregnant women with T1D. We aimed to investigate glycemic control and perinatal outcomes in pregnant women with T1D in a Chinese population and explored the role of metformin in these patients.MethodsWe obtained data of 38 pregnant women with T1D who received regular antenatal care and delivered at Peking Union Medical College Hospital (PUMCH) between 1 January 2006 and 31 May 2018. The perinatal outcomes of T1D patients who added metformin as adjunct treatment and those who remained on insulin-alone therapy were compared retrospectively.ResultsBeing overweight was common (35.1%) in pregnant women with T1D. On average, the insulin dose increased by 35.30 ± 22.60 unit/day during pregnancy. The cesarean delivery rate was high (65.8%), and fetal macrosomia was the main reason. The change of HbA1c in the metformin-insulin group was more prominent than in the insulin-only group (− 1.47 ± 1.17% vs. − 0.90 ± 1.13%, p = 0.05). There was no statistically significant difference in perinatal outcomes between the two groups.ConclusionsThe incidence of adverse perinatal outcomes in pregnant women with T1D was high. This study innovatively suggested that metformin could be safe and could contribute to improving glucose management in pregnant women with T1D.

Exploring the use of metformin in pregnant women with polycystic ovary syndrome: new evidence, new wisdom

Exploring the use of metformin in pregnant women with polycystic ovary syndrome: new evidence, new wisdom

The pros and cons of application of metformin in the pregnant women with polycystic ovary syndrome

Patients with polycystic ovary syndrome (PCOS) are often confronted with adverse pregnancy outcomes. There is accumulating evidence demonstrating that metformin increases the rate of pregnancy and reduces the occurrence of miscarriage. However, the lack of sufficient evidence for metformin in reducing gestational diabetes mellitus (GDM) and preeclampsia as well as its long-term safety data for offspring were also noted. The application of metformin in pregnant women with PCOS remains controversial. PCOS is a disease of great heterogeneity. With an increasing understanding of the pathogenesis of PCOS, the individualized treatment is a future trend as the patients with PCOS should be accurately classified to achieve the maximum benefit when metformin is added during pregnancy. (Chin J Endocrinol Metab, 2018, 34: 809-813) Key words: Polycystic ovary syndrome; Pregnancy; Metformin

Metformin in the management of diabetes during pregnancy and lactation.

This review explores the current place of metformin in the management of gestational diabetes (GDM) and type 2 diabetes during pregnancy and lactation. The rationale and basic pharmacology of metformin usage in pregnancy is discussed along with the evidence from observational and randomized controlled trials in women with GDM or overt diabetes. There seems to be adequate evidence of efficacy and short-term safety of metformin in relation to maternal and neonatal outcomes in GDM, with possible benefits related to lower maternal weight gain and lower risk of neonatal hypoglycemia and macrosomia. Additionally, metformin offers the advantages of oral administration, convenience, less cost and greater acceptability. Metformin may, therefore, be considered in milder forms of GDM where glycemic goals are not attained by lifestyle modification. However, failure rate is likely to be higher in those with an earlier diagnosis of GDM, higher blood glucose, higher body mass index (BMI) or previous history of GDM, and insulin remains the cornerstone of pharmacological treatment in such cases. The use of metformin in type 2 diabetes has been assessed in observational and small randomized trials. Metformin monotherapy in women with overt diabetes is highly unlikely to achieve glycemic targets. Hence, the use should be restricted as adjunct to insulin and may be considered in women with high insulin dose requirements or rapid weight gain. There is clearly a need for more clinical trials to assess the effect of combined insulin plus metformin therapy in pregnancy with type 2 diabetes. Additionally, there is a paucity of data on long-term effects in offspring exposed to metformin in utero. It is imperative to further explore its impact on offspring as metformin has significant transplacental transfer and has the potential to impact the programming of the epigenome. Therefore, caution must be exercised when prescribing metformin in pregnant women. More research is clearly needed before metformin can be considered as standard of care in the management of diabetes during pregnancy.

Metformin treatment of type 2 diabetes mellitus in pregnancy: update on safety and efficacy.

With the increasing prevalence of type 2 diabetes mellitus (T2DM) in women of childbearing age, prescribing antidiabetic medications in first-trimester pregnancy is becoming more common. Metformin treatment during this time is usually avoided in countries with well-resourced healthcare. This is based on historical concerns about safety to the foetus and the widespread availability of insulin. However, there is now increasing interest in the potential benefits of metformin in pregnant women with T2DM. In this commentary, the main evidence supporting metformin safety in pregnancy is summarized, with an emphasis on the first trimester. Based on a structured literature search, the recent randomized controlled trials comparing metformin and insulin are reviewed. We then show that prescribing advice for metformin in pregnancy is inconsistent and product information/package inserts (PI) are universally out of date. This causes confusion and pushes some women and their clinicians to change from metformin to insulin. The potential advantages of metformin in pregnant women with T2DM are then discussed, including oral dosing and improved acceptability, lower resource utilization and cost, decreased insulin requirements, less maternal weight gain and less risk of maternal and neonatal hypoglycaemia. The conclusion is that metformin is a cheap and efficacious antidiabetic medication for many pregnant women with T2DM, with reasonable evidence for safety. Drug information resources should be updated so that metformin can be considered more broadly in women with T2DM who present for antenatal care.

Metformin in pregnancy

Metformin in pregnancy

Metformin Safety in the Management of Gestational Diabetes

The use of metformin in pregnant women is still controversial, despite the increasing reports on metformin's safety and effectiveness. We aimed to evaluate the maternal and neonatal safety of metformin in subjects with gestational diabetes mellitus (GDM). We retrospectively reviewed the clinical records of 186 pregnancies complicated with GDM surveilled at Hospital de Santa Maria, Lisboa, between 2011 and 2012. The maternal and neonatal outcomes of 32 females who took metformin during pregnancy were compared with 121 females controlled with diet and 33 insulin-treated females. Of the 186 GDM subjects, 32 (17.2%) received metformin during pregnancy. No statistical differences between the diet and metformin groups were found with regard to the rates of abortion, prematurity, preeclampsia, macrosomy, small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns, cesarean deliveries, neonatal intensive care unit (NICU) admissions, and birth malformations or neonatal injuries. Similarly, there were no differences between the metformin and insulin groups with regard to the referred outcomes. No abortions or perinatal deaths were recorded in the metformin group. Ten out of 32 metformin patients required additional insulin. This retrospective study suggests that metformin is a safe alternative or additional treatment to insulin in females with GDM. Metformin was not associated with a higher risk of maternal or neonatal complications when compared to the insulin or diet groups.

A second look at the ancient drug: new insights into metformin.

Metformin, a biguanide derived from Galega officinalis (French lilac), has been used for the treatment of type 2 diabetes (T2D) for over half century. It is now the most widely prescribed anti-diabetic drug and recommended as the first line oral therapy for T2D. Metformin is generally considered as a very safe drug with favorable cost-efficacy-ratio. With regard to the safety concern of its use in gestational diabetes, Bertoldo et al. provided us an excellent summary of the current knowledge on the role of metformin in pregnant women as well as in fetal development. In addition to its use in T2D, metformin has also been prescribed for polycystic ovary syndrome (PCOS). In this issue, Neil P. Johnson reviewed the best available evidence for the use of metformin in women with PCOS and discussed its position among other options used to treat various problems faced by women with PCOS. In recent years, metformin has gained a lot of attention for its potential application in the prevention and treatment of cancer. The idea of cancer preventive and therapeutic effect of metformin originates from a serious of observational studies in populations with or without metformin consumption. Compared to its definitive performance in diabetic patients, the exact mechanism(s) of action and the direct molecular target(s) of metformin are less conclusive. In this special issue, Kasznicki et al. provided us an overview of proposed mechanism(s) of action of metformin in cancer prevention and therapy, along with preclinical and clinical data suggesting its favorable effect against cancer in different populations. The role of metformin on selective modulation of microRNAs to reprogram altered metabolism of a cancer cell toward that of untransformed cell was extensively reviewed by Pulito et al. Considering the crucial role of microRNAs in cancer stem cells (CSCs) or stem cell-like cancer cells, which are believed to be difficult to eradicate by various treatments, Bao et al. further discussed the potential role of metformin in modulaing CSC-associated microRNAs as part of the novel mechanism of action of metformin in the development and progression of breast and pancreatic cancers. Aside from the anti-tumor effect of metformin, Dr. Vladimir N. Anisimov presented a critical review regarding the capacity of metformin to prevent spontaneous and induced tumorigenesis based on published data derived from animal studies in an attempt to address the question “do metformin a real anticarcinogen”. Despite the popularity of metformin in the field of cancer research, it is not negligible that concerns have been raised towards various observational studies indicating that metformin use may reduce the incidence and/or mortality of different types of cancer. In order to help us uncover the veil of mysterious biases occured during these cohort studies, which have been mostly critized, Yang and Chan reviewed and discussed in detail the methodologies employed in metformin-related observational studies. Another paradox that metformin is facing is whether it acts against or towards cognitive impairment and Alzheimer disease in patients with T2D. In two separate editorials, European scientists Ilker Tasci and Paula I. Moreira presented their own opinion towards this controversy. Herein, I would like to acknowledge each and every one who has devoted their time and efforts to this special issue. We believe this issue has included most up-to-date information regarding the conventional use of metformin as well as the potential expansion of its applications. Hopefully our readers will enjoy and benefit from reading this special issue.

Metformin vs insulin in the management of gestational diabetes: a meta-analysis.

BackgroundNowadays, there have been increasing studies comparing metformin with insulin. But the use of metformin in pregnant women is still controversial, therefore, we aim to examine the efficiency and safety of metformin by conducting a meta-analysis of randomized controlled trials (RCTs) comparing the effects of metformin with insulin on glycemic control, maternal and neonatal outcomes in gestational diabetes mellitus (GDM).MethodsWe used the key words “gestational diabetes” in combination with “metformin” and searched the databases including Pubmed, the Cochrane Library, Web of knowledge, and Clinical Trial Registries. A random-effects model was used to compute the summary risk estimates.ResultsMeta-analysis of 5 RCTs involving 1270 participants detected that average weight gains after enrollment were much lower in the metformin group (n = 1006, P = 0.003, SMD = −0.47, 95%CI [−0.77 to −0.16]); average gestational ages at delivery were significantly lower in the metformin group (n = 1270, P = 0.02, SMD = −0.14, 95%CI [−0.25 to −0.03]); incidence of preterm birth was significantly more in metformin group (n = 1110, P = 0.01, OR = 1.74, 95%CI [1.13 to 2.68]); the incidence of pregnancy induced hypertension was significantly less in the metformin group (n = 1110, P = 0.02, OR = 0.52, 95%CI [0.30 to 0.90]). The fasting blood sugar levels of OGTT were significantly lower in the metformin only group than in the supplemental insulin group (n = 478, P = 0.0006, SMD = −0.83, 95%CI [−1.31 to −0.36]).ConclusionsMetformin is comparable with insulin in glycemic control and neonatal outcomes. It might be more suitable for women with mild GDM. This meta-analysis also provides some significant benefits and risks of the use of metformin in GDM and help to inform further development of management guidelines.

The efficacy of metformin in pregnant women with polycystic ovary syndrome: a meta-analysis of clinical trials.

The role of metformin in the treatment of pregnant women with polycystic ovary syndrome (PCOS) is controversial. Therefore, we evaluated whether the use of metformin during pregnancy in women with PCOS could reduce pregnancy-related complications. MEDLINE was searched to retrieve relevant trials. In addition, reviews and reference lists of the retrieved articles were scanned for further appropriate studies. The primary outcome measure was the incidence of complications of pregnancy, which included early pregnancy loss (EPL), gestational diabetes (GDM), pre-eclampsia (PE), and pre-term delivery (PD). In total, eight studies with 1106 patients were included. The pooled odds ratio (OR) (95% confidence interval) of outcome for pregnant women with PCOS prescribed metformin were 0.32 (0.19-0.55) for EPL, 0.37 (0.25-0.56) for GDM, 0.53 (0.30-0.95) for PE and 0.30 (0.13-0.68) for PD. Metformin therapy throughout pregnancy decreased the OR of EPL, GDM, PE, and PD in pregnant PCOS women with no serious detrimental side effects.