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Does Metformin Cross The Placenta

Is Metformin Therapy For Polycystic Ovary Syndrome Safe During Pregnancy?

Is Metformin Therapy For Polycystic Ovary Syndrome Safe During Pregnancy?

Abstract Abstract: Polycystic ovary syndrome is characterized among other things by oligo-amenorrhea and may account for more than 75% of cases with anoluvatory infertility. Due to its positive effects on polycystic ovary syndrome-induced infertility metformin has become one of the most common drugs used in this group of patients. The efficacy of the drug as well as the first reports on metformin used in pregnancy has encouraged the continued use of the drug after conception. This MiniReview reviews the current pros and cons of metformin use in pregnancy while awaiting the results of ongoing randomised, controlled clinical trials addressing the subject. Polycystic ovary syndrome is characterized by oligo-amenorrhea, clinical and/or biochemical hyperandrogenism (hirsutism, acne, increased testosterone levels in plasma) and polycystic ovaries, and may account for more than 75% of cases with anovulatory infertility (Laven et al. 2002). Polycystic ovary syndrome is accompanied by a very high risk for developing one or more elements of the metabolic syndrome (obesity, type-2 diabetes, hypertension, dyslipidaemia) (Legro 2001; Ben Haroush et al. 2004). This is particularly true in overweight patients with polycystic ovary syndrome. The condition is extremely frequent, affecting as much as 15–20% of fertile women in some populations. Apart from infertility, hyperandrogenism and the metabolic syndrome, polycystic ovary syndrome may predispose to premature development of hormone-sensitive cancers (Balen 2001; Riman et al. 2004). One of the main objectives of treatment in polycystic ovary syndromes is the reestablishment of a normal ovulatory pattern and thereby fertility. A number of treatments are available in this syndrome. Hypocaloric diets and exercise for the improvement Continue reading >>

Drug Use During Pregnancy

Drug Use During Pregnancy

More than 50% of pregnant women take prescription or nonprescription (over-the-counter) drugs or use social drugs (such as tobacco and alcohol) or illicit drugs at some time during pregnancy, and use of drugs during pregnancy is increasing. In general, drugs should not be used during pregnancy unless necessary because many can harm the fetus. About 2 to 3% of all birth defects result from drugs that are taken to treat a disorder or symptom. Sometimes drugs are essential for the health of the pregnant woman and the fetus. In such cases, a woman should talk with her doctor or other health care practitioner about the risks and benefits of taking the drug. Before taking any drug (including over-the-counter drugs) or dietary supplement (including medicinal herbs), a pregnant woman should consult her health care practitioner. A health care practitioner may recommend that a woman take certain vitamins and minerals during pregnancy. Drugs taken by a pregnant woman reach the fetus primarily by crossing the placenta, the same route taken by oxygen and nutrients, which are needed for the fetus's growth and development. Drugs that a pregnant woman takes during pregnancy can affect the fetus in several ways: They can act directly on the fetus, causing damage, abnormal development (leading to birth defects), or death. They can alter the function of the placenta, usually by causing blood vessels to narrow (constrict) and thus reducing the supply of oxygen and nutrients to the fetus from the mother. Sometimes the result is a baby that is underweight and underdeveloped. They can cause the muscles of the uterus to contract forcefully, indirectly injuring the fetus by reducing its blood supply or triggering preterm labor and delivery. They can also affect the fetus indirectly. For example Continue reading >>

Metformin For Gestational Diabetes - What It Is And How It Works

Metformin For Gestational Diabetes - What It Is And How It Works

In the UK it is common to use Metformin for gestational diabetes where dietary and lifestyle changes are not enough to lower and stabilise blood sugar levels. It is widely used to help lower fasting blood sugar levels as well as post meal levels. Metformin is an oral medication in tablet form. It is used in diabetics to help the body use insulin better by increasing how well the insulin works. In pregnancy it can be used in women who have diabetes before becoming pregnant (Type 2 diabetes) and in women who develop diabetes during pregnancy (gestational diabetes). Metformin is also used for other conditions too, commonly used in those that have PCOS (polycystic ovarian syndrome). Metformin is a slow release medication. Here are the most commonly asked Q&A on Metformin for gestational diabetes from our Facebook support group Why do I need to take Metformin? For many ladies with gestational or type 2 diabetes, if lower blood sugar levels cannot be reached through diet and exercise then medication will be required to assist. If blood sugar levels remain high, then the diabetes is not controlled and can cause major complications with the pregnancy and baby. Some consultants will prescribe Metformin on diagnosis of gestational diabetes on the basis of your GTT results. Others will let you try diet control first and when blood glucose levels rise out of target range, or close to the target range, they may prescribe Metformin as a way to help lower and control your levels. NICE guidelines regarding the timing and use of Metformin for gestational diabetes 1.2.19 Offer a trial of changes in diet and exercise to women with gestational diabetes who have a fasting plasma glucose level below 7 mmol/litre at diagnosis. [new 2015] 1.2.20 Offer metformin[4] to women with gestational dia Continue reading >>

Metformin Therapy And Diabetes In Pregnancy

Metformin Therapy And Diabetes In Pregnancy

Summary No adverse pregnancy outcomes with metformin use have been reported, except in one unmatched study. Otherwise, the studies are small and non-randomised, with the exception of one prospective, randomised controlled trial, currently under way, comparing metformin with insulin in women with gestational diabetes mellitus (the MiG trial). No long-term follow-up data for offspring of mothers receiving metformin have been published. Any woman with diabetes should be as close to euglycaemia as possible before pregnancy. In some circumstances (eg, severe insulin resistance), metformin therapy during pregnancy may be warranted. When metformin treatment is being considered, the individual risks and benefits need to be discussed with the patient so that an appropriate decision can be reached. Continue reading >>

Metformin In Pregnancy And Lactation

Metformin In Pregnancy And Lactation

Metformin improves insulin sensitivity and reduces hepatic glucose output in patients with diabetes. It offers potential benefits for pregnant women with gestational or type 2 diabetes because both conditions are associated with increased insulin resistance. Some cohort data are available and randomised trials are currently in progress to compare metformin with insulin, but strong evidence is not yet available to guide management. There are no long-term follow-up data to provide reassurance about the safety of metformin, given its passage across the placenta, although recent evidence suggests that there is no significant risk of teratogenesis. Limited amounts of metformin are transferred into breast milk, but the risk of neonatal hypoglycaemia is negligible. Introduction Oral hypoglycaemic drugs have been viewed with suspicion for many years in the management of women with diabetes during pregnancy or breastfeeding. Pregnant women with type 2 diabetes are often switched to insulin. However, there is long experience with use of the biguanide metformin in pregnant women in South Africa. Metformin increases insulin sensitivity, reduces hepatic glucose release and is associated with a tendency to lose weight.1 Increasingly metformin is being used in the management of women with polycystic ovary syndrome, as the syndrome is associated with insulin resistance. Metformin reduces hyperandrogenaemia and, as it allows more effective ovulation to occur, it is now widely used in the management of infertility.2 If a woman with polycystic ovary syndrome becomes pregnant while taking metformin, a decision has to be made whether to continue treatment. Teratogenicity Caution is needed when using metformin in pregnancy. In the Australian categorisation of risk metformin is in category C. Continue reading >>

Metformin Therapy During Pregnancy: Good For The Goose And Good For The Gosling Too?

Metformin Therapy During Pregnancy: Good For The Goose And Good For The Gosling Too?

Type 2 diabetes and gestational diabetes mellitus (GDM) are closely related disorders characterized by increased insulin resistance. Metformin, a biguanide compound, exerts its clinical effect by both reducing hepatic glucose output and by increasing insulin sensitivity. This results in a decreased glucose level without an associated high risk of either hypoglycemia or weight gain. These characteristics have established metformin as an ideal first-line treatment for people with type 2 diabetes and, hypothetically, a particularly attractive drug for use in pregnancy. However, metformin is known to cross the placenta (1,2), and its use in pregnancy has been limited by concerns regarding potential adverse effects on both the mother and the fetus. Historically, some of the earliest reports of the use of metformin during pregnancy have come from South Africa, where it has been used since the late 1970s for women with both type 2 diabetes and GDM (3–6). While perinatal mortality for these women was still higher than that seen in the general obstetric population, it was nonetheless lower than in women who had gone untreated and similar to those who were changed to insulin. No “headline” adverse events or side effects were reported. Confidence regarding the use of metformin in pregnancy has been reinforced by the results of several observational studies and randomized trials over the past decade. Two meta-analyses of observational studies—one of women using metformin and/or sulphonylureas and one of women using metformin alone during the first trimester—did not show an increase in congenital malformations or neonatal deaths (7,8). While increased perinatal mortality and pre-eclampsia was noted in … Discover the world's research 14+ million members 100+ million publi Continue reading >>

Metformin In Pregnancy And Lactation

Metformin In Pregnancy And Lactation

Metformin improves insulin sensitivity and reduces hepatic glucose output in patients with diabetes. It offers potential benefits for pregnant women with gestational or type 2 diabetes because both conditions are associated with increased insulin resistance. Some cohort data are available and randomised trials are currently in progress to compare metformin with insulin, but strong evidence is not yet available to guide management. There are no long-term follow-up data to provide reassurance about the safety of metformin, given its passage across the placenta, although recent evidence suggests that there is no significant risk of teratogenesis. Limited amounts of metformin are transferred into breast milk, but the risk of neonatal hypoglycaemia is negligible. Introduction Oral hypoglycaemic drugs have been viewed with suspicion for many years in the management of women with diabetes during pregnancy or breastfeeding. Pregnant women with type 2 diabetes are often switched to insulin. However, there is long experience with use of the biguanide metformin in pregnant women in South Africa. Metformin increases insulin sensitivity, reduces hepatic glucose release and is associated with a tendency to lose weight.1 Increasingly metformin is being used in the management of women with polycystic ovary syndrome, as the syndrome is associated with insulin resistance. Metformin reduces hyperandrogenaemia and, as it allows more effective ovulation to occur, it is now widely used in the management of infertility.2 If a woman with polycystic ovary syndrome becomes pregnant while taking metformin, a decision has to be made whether to continue treatment. Teratogenicity Caution is needed when using metformin in pregnancy. In the Australian categorisation of risk metformin is in category C. Continue reading >>

Role Of Insulin In Placental Transport Of Nutrients In Gestational Diabetes Mellitus

Role Of Insulin In Placental Transport Of Nutrients In Gestational Diabetes Mellitus

Abstract Background: Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown. Summary: There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary. © 2017 S. Karger AG, Basel Introduction Gestational diabetes mellitus (GDM) is associated with perinatal complications, such as macrosomia in the offspring and increased fetal adiposity, which may increase the risk of obesity, diabetes type 2, and metabolic syndrome in adulthood [1]. Pregnant women diagnosed with gestational diabetes are treated through diet (and exercise) or with insulin in order to avoid hyperglycemia and its adverse effects on fetal development. However, during recent y Continue reading >>

Metformin Therapy During Pregnancy

Metformin Therapy During Pregnancy

Type 2 diabetes and gestational diabetes mellitus (GDM) are closely related disorders characterized by increased insulin resistance. Metformin, a biguanide compound, exerts its clinical effect by both reducing hepatic glucose output and by increasing insulin sensitivity. This results in a decreased glucose level without an associated high risk of either hypoglycemia or weight gain. These characteristics have established metformin as an ideal first-line treatment for people with type 2 diabetes and, hypothetically, a particularly attractive drug for use in pregnancy. However, metformin is known to cross the placenta (1,2), and its use in pregnancy has been limited by concerns regarding potential adverse effects on both the mother and the fetus. Historically, some of the earliest reports of the use of metformin during pregnancy have come from South Africa, where it has been used since the late 1970s for women with both type 2 diabetes and GDM (3–6). While perinatal mortality for these women was still higher than that seen in the general obstetric population, it was nonetheless lower than in women who had gone untreated and similar to those who were changed to insulin. No “headline” adverse events or side effects were reported. Confidence regarding the use of metformin in pregnancy has been reinforced by the results of several observational studies and randomized trials over the past decade. Two meta-analyses of observational studies—one of women using metformin and/or sulphonylureas and one of women using metformin alone during the first trimester—did not show an increase in congenital malformations or neonatal deaths (7,8). While increased perinatal mortality and pre-eclampsia was noted in one study of 50 women with type 2 diabetes using metformin, these result Continue reading >>

Screening, Diagnosis, And Management Of Gestational Diabetes Mellitus

Screening, Diagnosis, And Management Of Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) affects approximately 6% of pregnancies in the United States, and it is increasing in prevalence. Pregnant women without known diabetes mellitus should be screened for GDM after 24 weeks of gestation. Treatment of GDM results in a statistically significant decrease in the incidence of preeclampsia, shoulder dystocia, and macrosomia. Initial management includes glucose monitoring and lifestyle modifications. If glucose levels remain above target values, pharmacologic therapy with metformin, glyburide, or insulin should begin. Antenatal testing is customary for women requiring medications. Induction of labor should not occur before 39 weeks in women with GDM, unless glycemic control is poor or another indication for delivery is present. Unless otherwise indicated, scheduled cesarean delivery should be considered only in women with an estimated fetal weight greater than 4,500 g. Women with a history of GDM are at high risk of subsequently developing diabetes. These patients should be screened six to 12 weeks postpartum for persistently abnormal glucose metabolism, and should undergo screening for diabetes every three years thereafter. Gestational diabetes mellitus (GDM) is a condition of glucose intolerance with onset or first recognition in pregnancy that is not clearly overt diabetes.1,2 Normal pregnancy is characterized by pancreatic β-cell hyperplasia resulting in higher fasting and postprandial insulin levels. Increased secretion of placental hormones leads to increasing insulin resistance, especially throughout the third trimester. GDM occurs when β-cell function is insufficient to overcome this insulin resistance.3 Clinical recommendation Evidence rating References Comments Screening for GDM should occur after 24 weeks of gestat Continue reading >>

Human Placental Glucose Uptake And Transport Are Not Altered By The Oral Antihyperglycemic Agent Metformin☆☆☆★

Human Placental Glucose Uptake And Transport Are Not Altered By The Oral Antihyperglycemic Agent Metformin☆☆☆★

Abstract OBJECTIVE: Our purpose was to determine whether the biguanide oral antihyperglycemic agent metformin increases human placental uptake and transport of glucose to the fetal circulation. STUDY DESIGN: The human single-cotyledon model was used to compare transport of tritiated glucose in the maternal to fetal direction in eight human placentas between control placentas and those exposed to metformin in vitro. Transport was calculated from the serial perfusate glucose levels obtained in each 3-hour experiment, and placental uptake was determined from homogenates of the perfused cotyledon. Liquid scintillation spectrometry measured levels of both glucose and the reference substance antipyrine. Transport was compared by the Mann-Whitney U test. RESULTS: Mean maternal and fetal glucose levels were 77.5 ± 4.9 mg/dl and 61.3 ± 5.9 mg/dl, respectively, in the metformin group and 83.8 ± 4.3 mg/dl and 60.4 ± 12.4 mg/dl, respectively, in controls at 2 hours. Placental glucose uptake was 91.1 ± 42.2 μg/gm placenta in the metformin experiments and 104.9 ± 76.9 μg/gm placenta in controls. No difference in placental glucose uptake or transport could be demonstrated. CONCLUSION: Metformin does not affect human placental glucose uptake or transport.(Am J Obstet Gynecol 1997;176:527-30.) Continue reading >>

Pharmacokinetics Of Metformin During Pregnancy

Pharmacokinetics Of Metformin During Pregnancy

Our objective was to evaluate the pharmacokinetics of metformin during pregnancy. Serial blood and urine samples were collected over one steady-state dosing interval in women treated with metformin during early to late pregnancy (n = 35) and postpartum (n = 16). Maternal and umbilical cord blood samples were obtained at delivery from 12 women. Metformin concentrations were also determined in breast milk samples obtained over one dosing interval in 6 women. Metformin renal clearance increased significantly in mid (723 ± 243 ml/min, P < 0.01) and late pregnancy (625 ± 130 ml/min, P < 0.01) compared with postpartum (477 ± 132 ml/min). These changes reflected significant increases in creatinine clearance (240 ± 70 ml/min, P < 0.01 and 207 ± 56 ml/min, P < 0.05 versus 165 ± 44 ml/min) and in metformin net secretion clearance (480 ± 190 ml/min, P < 0.01 and 419 ± 78 ml/min, P < 0.01 versus 313 ± 98 ml/min) in mid and late pregnancy versus postpartum, respectively. Metformin concentrations at the time of delivery in umbilical cord plasma ranged between nondetectable (<5 ng/ml) and 1263 ng/ml. The daily infant intake of metformin through breast milk was 0.13 to 0.28 mg, and the relative infant dose was <0.5% of the mother’s weight-adjusted dose. Our results indicate that metformin pharmacokinetics are affected by pregnancy-related changes in renal filtration and net tubular transport and can be roughly estimated by the use of creatinine clearance. At the time of delivery, the fetus is exposed to metformin concentrations from negligible to as high as maternal concentrations. In contrast, infant exposure to metformin through the breast milk is low. Metformin is an effective oral hypoglycemic agent that improves insulin sensitivity (Krentz and Bailey, 2005). The introdu Continue reading >>

Oral Therapy In Dm With Pregnancy

Oral Therapy In Dm With Pregnancy

By Prof. ADEL A EL-SAYED MD Prof. of Internal Medicine Sohag Faculty of Medicine Sohag-EGYPT Classic Statement If diet and exercise do not lead to adequate glycemic control in a woman with gestational diabetes, then insulin should be given. Oral hypoglycemic drugs, particularly the sulfonylurea drugs, are contraindicated during pregnancy. Davis SN, Granner DK. Insulin, oral hypoglycemic agents, and the pharmacology of the endocrine pancreas. In: Hardman JG, Limbird LE, eds. Goodman and Gilman's the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill, 1996:1509. Classic Statement In a recent policy statement by the American Diabetes Association and the American College of Obstetricians and Gynecologists, “Oral glucose lowering agents have generally not been recommended during pregnancyâ€. American Diabetes Association: Gestational diabetes mellitus. Diabetes Care 27 (Suppl. 1):S88 –S90, 2004. Problems With Oral Therapy Hyperinsulinemia First-generation sulfonylureas (tolbutamide and chlorpropamide) can easily cross the placenta leading to almost similar cord and maternal serum concentrations. Stowers JM, Sutherland HW. The use of sulphonylureas biguanides and insulin in pregnancy. In: Sutherland HW, Stowers JM, eds. Carbohydrate metabolism in pregnancy and the newborn. Edinburgh, Scotland: Churchill Livingstone, 1975:205-20. Early experience with these drugs included numerous cases of profound and prolonged neonatal hypoglycemia. Zucker P, Simon G. Prolonged symptomatic neonatal hypoglycemia associated with maternal chlorpropamide therapy. Pediatrics 1968;42:824-825 Problems With Oral Therapy? Teratogenicity Retrospective studies of series of women with type 2 diabetes mellitus suggested an association between first-trimester sulfonylurea Continue reading >>

Efficacy And Safety Of Metformin During Pregnancy In Women With Gestational Diabetes Mellitus Or Polycystic Ovary Syndrome: A Systematic Review.

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. © 2013. Continue reading >>

Gestational Diabetes Should You Use Oral Agents?

Gestational Diabetes Should You Use Oral Agents?

Although both glyburide and metformin cross the placental barrier, they appear to be safe to use in treating gestational diabetes. Glyburide and metformin provide effective, convenient, inexpensive alternatives to treatment with insulin. Safety The safety of any drug used in pregnancy depends on whether it crosses the placenta and its effects on the fetus. Many drugs commonly used in pregnancy (eg, magnesium) cross the placenta and exert effects on the fetus, so crossing the placenta alone does not automatically preclude use in pregnancy. Glyburide is a second-generation sulfonylurea that is metabolized by the liver. It works by stimulating the pancreas to produce more insulin. Patients with allergies to sulfa-containing agents should not take this drug. Peak plasma levels of glyburide occur within 4 hours. The US Food and Drug Administration (FDA) categorizes glyburide as a pregnancy Category B drug. Side effects include nausea, vomiting, diarrhea, and pruritic rash. Using a placental cotyledon model of perfusion, Elliott and colleagues demonstrated insignificant transport of glyburide across the placenta.8 Using the same model, Kraemer et al identified active transport of glyburide from the fetal to the maternal circulation, which may help protect the fetus from exposure to the drug.9 Langer et al tested cord blood at delivery and compared it with maternal serum collected simultaneously.10 No neonates had measurable amounts of glyburide in spite of identification of the drug in maternal serum. One study, designed to examine the pharmacokinetics of glyburide in pregnancy, found that cord blood concentrations of glyburide were 70% of maternal serum concentrations.11 Other studies indicate that fetal concentrations of glyburide may be 1% to 2% of maternal concentration.1 Continue reading >>

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