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Does Metformin Cross The Placenta

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 >>

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 >>

Impact Of Metformin On Reproductive Tissues: An Overview From Gametogenesis To Gestation

Impact Of Metformin On Reproductive Tissues: An Overview From Gametogenesis To Gestation

Michael J. Bertoldo*, Melanie Faure*, Joelle Dupont, Pascal Froment Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Centre Val de Loire, UMR85, 37380 Nouzilly, France *These authors contributed equally to this work. Correspondence to: Dr. Pascal Froment. Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, 37380 Nouzilly, France. Email: [email protected] Abstract: Metformin is an oral anti-hyperglycemic drug that acts as an insulin sensitizer in the treatment of diabetes mellitus type 2. It has also been widely used in the treatment of polycystic ovary syndrome (PCOS) and gestational diabetes. This drug has been shown to activate a protein kinase called 5' AMP-activated protein kinase or AMPK. AMPK is present in many tissues making metformin’s effect multi factorial. However as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus. The majority of reports suggest no significant adverse effects or teratogenicity. However, disconcerting reports of male mouse offspring that were exposed to metformin in utero that present with a reduction in testis size, seminiferous tubule size and in Sertoli cell number suggest that we do not understand the full suite of effects of metformin. In addition, recent molecular evidence is suggesting an epigenetic effect of metformin which could explain some of the long-term effects reported. Nevertheless, the data are still insufficient to completely confirm or disprove negative effects of metformin. The aims of this review are to provide a summary of the safety of metformin in various aspects of sexual reproduction, the use of metform Continue reading >>

2017 Ada Guidelines: Diabetes During Pregnancy

2017 Ada Guidelines: Diabetes During Pregnancy

Below you can find ADA standards on proper A1c targets, blood pressure range, retinopathy monitoring and medications used in preexisting and gestational diabetes. The preferred medications during pregnancy are insulin, metformin and glyburide. Recommendations are listed below with slightly modified wording for easier and succinct reading: GT Diabetes Care ADA Guidelines January 2017 Preexisting Diabetes Preconception counseling should address the importance of glycemic control as close to normal as is safely possible, ideally A1C <6.5% to reduce the risk of congenital anomalies. Women with preexisting type 1 or type 2 diabetes who are planning pregnancy or who have become pregnant should be counseled on the risk of development and/or progression of diabetic retinopathy. Dilated eye examinations should occur before pregnancy or in the first trimester, and then patients should be monitored every trimester and for 1 year postpartum as indicated by degree of retinopathy and as recommended by the eye care provider. Gestational Diabetes Mellitus Lifestyle change is an essential component of management of gestational diabetes mellitus and may suffice for the treatment for many women. Medications should be added if needed to achieve glycemic targets. Insulin is the preferred medication for treating hyperglycemia in gestational diabetes mellitus, as it does not cross the placenta to a measurable extent. Metformin and glyburide may be used, but both cross the placenta to the fetus, with metformin likely crossing to a greater extent than glyburide. All oral agents lack long-term safety data. Metformin, when used to treat polycystic ovary syndrome and induce ovulation, need not be continued once pregnancy has been confirmed. General Principles Potentially teratogenic medications (A 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 >>

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 >>

Diabetes And Pregnancy

Diabetes And Pregnancy

Diabetes in pregnancy is called gestational diabetes mellitus and is a serious condition if not properly diagnosed and managed. Newborns exposed to mothers that have high circulating glucose levels in their blood (hyperglycemia) during pregnancy have a high risk of being born overweight and of eventually becoming obese children and adults. These newborns also are at a high risk of developing diabetes themselves later in life. Pregnancy diabetes is increasing in every ethnic group. A majority of women with pregnancy diabetes will acquire overt type 2 diabetes within 5 years. Several studies have given us a body of supplementary science showing that exposure to high blood glucose in utero causes accumulation of fat in the fetus. Even though that baby fat might be lost in early childhood, exposure during pregnancy nevertheless genetically programs the fetus for a higher risk of developing fatness as an adult. However,there are studies that show that interventions to control blood glucose are effective in reducing rates of newborn obesity and therefore should improve adolescent and adult health downstream. There is a positive impact of treating even mild forms of pregnancy diabetes with the largest effects being on reducing newborn obesity. In a study by Dr. Mark Landon, more than 90% of the women needed only dietary counseling and education about blood glucose control for effective treatment of abnormal blood glucose levels. Surprisingly, fewer than 10% needed insulin as well Doctors need to be vigilant in detecting pregnancy diabetes because the maximal time of fetal fat accretion is at about in the 7th to 8th month of pregnancy( 32-34 weeks’ gestation). Pregnancy diabetes is typically diagnosed at about 6th-7th month of pregnancy (28 weeks’ gestation), and patients u Continue reading >>

Metformin And Pregnancy: Is It Safe For My Baby?

Metformin And Pregnancy: Is It Safe For My Baby?

Summary: Metformin has gained popularity as another option to treat gestational diabetes. It appears to be safe for baby and mother. However, the human data is still limited and metformin can have potential, and serious, side effects. Also, there is concern that metformin may cross the placental barrier and reach the fetus. Dear Curtis: During my last pregnancy I got gestational diabetes. I’m trying to get pregnant again but obviously my doctor and I are concerned about the possibility of getting the gestational diabetes again. Last time I tried diet and some insulin. But this time I’d like to avoid insulin. My doctor mentioned adding metformin (a diabetes medications). Is this any safer for me and the baby? • Each drug on the market has a pregnancy rating. Metformin is a pregnancy category B. The higher the letter, the safer the drug is. So, metformin, as far as we know, is relatively safe during pregnancy. But there is more to the story. Blood Glucose Levels During Pregnancy First of all, why be so concerned about blood sugars during pregnancy? Well, while it’s not 100% proven just yet, it’s strongly believed that out-of-whack blood sugars during pregnancy can be harmful to the developing baby. Namely, it can lead to birth defects. To try and prevent that doctors do their best to keep blood sugars in check through diet and – when needed – insulin. You’ve already gone the insulin route and – understandably – didn’t care for it. Because of women like yourself doctors have begun using oral diabetes medications like glyburide and metformin. The problem? Despite a pregnancy category B rating for metformin we really don’t have a lot of scientific information on what the long term effects of metformin are on the fetus. I mean, we just don’t design s 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 >>

Evidence Shows Possible Benefit Of Metformin And Glyburide Use In Pregnancy

Evidence Shows Possible Benefit Of Metformin And Glyburide Use In Pregnancy

A review of recent studies suggests that some oral hypoglycemic agents may be safe and effective in pregnant patients…. Insulin is traditionally the treatment of choice in pregnant patients requiring medication to manage their blood glucose levels, as it is a hormone the body already produces naturally and should therefore theoretically pose less risk to a developing fetus. New evidence, however, suggests that certain oral hypoglycemic agents may be suitable alternatives for these patients. These oral agents would help to simplify medication regimens in many of these patients, as insulin administration is known to be demanding, unpleasant, and inconvenient. A literature search was performed using Pubmed and other electronic databases to identify articles pertaining to this topic. In particular, the keywords pregnancy, diabetes, and the names of different oral hypoglycemic agents were used to find this information. Manufacturers of different oral agents were also contacted for further information. Studies found metformin to be safe for use throughout pregnancy, and to be associated with several additional benefits. These include: reduced pregnancy loss, less maternal weight gain, and less neonatal hypoglycemia. Also, several studies found an up to 10-fold reduction in incident gestational diabetes in women treated with metformin. A trial is currently being conducted to examine whether it is beneficial to begin metformin therapy in pregnant type 2 diabetics treated with insulin, as previous studies focus on type 1. Randomized controlled trials in patients with gestational diabetes found no difference in a composite of neonatal complications between patients taking metformin and patients using insulin. Metformin was also found to have a higher treatment satisfaction rate 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 >>

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 >>

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 >>

9 Metformin Treatment For Type 2 Diabetes In Pregnancy?

9 Metformin Treatment For Type 2 Diabetes In Pregnancy?

Metformin lowers blood glucose by reducing hepatic glucose output, increasing insulin sensitivity and enhancing peripheral glucose uptake. Metformin is widely used in women with Type 2 diabetes of child-bearing age, many of whom become pregnant. Studies to date in Type 2 diabetes in pregnancy, gestational diabetes and polycystic ovarian syndrome are reassuring. Metformin is not considered teratogenic. There is sufficient evidence that metformin is safe used throughout pregnancy, with no worsening of obstetric or perinatal outcomes. Women may benefit from the lesser weight gain. The long-term risks to the offspring remain inadequately researched, with no evidence of harm up to 2 years, and no suggestions of later complications in countries using metformin for many years. Metformin is recommended for use in pregnancies complicated by Type 2 diabetes, but women should be informed of the evidence regarding its associated risks and benefits to enable an informed choice over its use. Continue reading >>

Type 1 Diabetes: The Latest Technology ​pumps And Sensors

Type 1 Diabetes: The Latest Technology ​pumps And Sensors

Is there a role for metformin in Gestational Diabetes? The standard of care for gestational diabetes has been lifestyle (diet changes (carbohydrate restriction) and activity) and if not at goal (fasting < 90-95 mg/dl, 1 hour after meal < 140, 2 hour < < 120) then insulin is used. However, there is a literature on the use of metformin and sulfonylureas (glyburide) in pregnancy. I do NOT recommend the use of sulfonylureas during pregnancy as insulin is safer and more effective. Its use may be justified in certain circumstances such as patient populations if insulin will not be available or used safely and effectively (and metformin is not tolerated) as improved glucose control may trump the potential side effects. A meta-analysis (BMJ January 21st 2015, 350:h102) found glibenclamide clearly inferior to both insulin and metformin. Metformin (plus insulin when needed) performed slightly better than insulin. Metformin is widely used in pregnancy but this remains a controversial area. Firstly and of interest, metformin is used in women with polycystic ovarian syndrome (PCOS) during the first trimester of pregnancy (when organ development is occurring) and there is clinical evidence this is safe and potentially cuts the risk of early miscarriage. The medical literature also supports the use of metformin. There are randomized clinical trials using metformin in the treatment of women with GDM. In the Metformin in Gestational Diabetes (MiG) trial (NEJM 2008;358:2003-2015, 751 women were randomized to receive either metformin or insulin. There was no significant difference in the composite fetal outcome between the two groups although preterm birth was found to be increased in the metformin group. Women in the metformin group had less weight gain compared with women in the insulin Continue reading >>

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