Comparison of Glibenclamide and Insulin on Neonatal Outcomes in Pregnant Women with Gestational Diabetes Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes Metformin Use in PCOS Pregnancies Increases the Risk of Offspring Overweight at 4 Years of Age: Follow-Up of Two RCTs A comparison between the pregnancy outcome of women with gestation diabetes treated with glibenclamide and those treated with insulin. Comparison of glyburide and insulin in women with gestational diabetes mellitus and associated perinatal outcome: a randomized clinical trial. Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational Diabetes: A Randomized Clinical Trial Metformin versus insulin for the treatment of gestational diabetes. Glyburide Transport Across the Human Placenta Neonatal adiposity following maternal treatment of gestational diabetes with glyburide compared with insulin. Insulin detemir versus glyburide in women with gestational diabetes mellitus A comparison of glyburide and insulin in women with gestational diabetes mellitus. Are We Optimizing Gestational Diabetes Treatment With Glyburide? The Pharmacologic Basis for Better Clinical Practice Use of glyburide for the treatment of gestational diabetes: the San Antonio experience. A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes. Research Gaps in Gestational Diabetes Mellitus: Executive Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop. Glyburide as treatment option for gestational diabetes mellitus.
Background : Untreated or poorly controlled gestational diabetes can cause serious complications for mother and newborn . Glibenclamide is rarely used in treating mothers with this disease . This study aim ed at comparing the effect of glibenclamide and insulin on neonatal outcomes in women with gestational diabetes mellitus . Methods : In this r and omized controlled clinical trial , 249 pregnant women aged 18–45 years within the 11th–33rd weeks of gestation with gestational diabetes , single fetus pregnancy , and in need of hyperglycemia treatment were entered and grouped r and omly as either glibenclamide or insulin . In the insulin group ( n = 129 ) , insulin was administered with an initial dose of 0.2 IU/kg subcutaneously twice per day , whereas in the glibenclamide group ( n = 120 ) , 1.25 mg oral glibenclamide was administered once daily and increased if needed . Results : The results showed no significant difference in means age , gestational age , and body mass index between women in the two groups . In addition , there were no significant differences in the frequency of neonatal hypoglycemia , anomaly , hyperbilirubinemia , admission in Neonatal Intensive Care Unit ( NICU ) , and neonatal respiratory distress between two groups . Macrosomia was lower in the glibenclamide group than the insulin group ( 3.3 % vs. 13.2 % , respectively , P = 0.005 ) . Regression logistics model results showed that the type of treatment ( odds ratio [ OR ] : 4.62 ; confidence interval [ CI ] : 1.45–14.02 ; P = 0.01 ) and gestational age at delivery ( OR : 1.41 ; CI : 1.04–1.74 ; P = 0.01 ) were as predictor factors of macrosomia . Conclusions : The results of this study revealed that glibenclamide is able to reduce the risk of fetal macrosomia without increasing neonatal anomalies , jaundice , hypocalcemia , infant respiratory distress , and NICU admission Objective . To examine perinatal outcomes in women with gestational diabetes mellitus treated with glyburide  compared to insulin injections . Study design . This is a retrospective cohort study of women diagnosed with gestational diabetes mellitus ( GDM ) who required pharmaceutical therapy and were enrolled in the Sweet Success California Diabetes and Pregnancy Program between 2001 and 2004 , a California state-wide program . Women managed with glyburide were compared to women treated with insulin injections . Perinatal outcomes were compared using chi-square test and multivariable logistic regression models ; statistical significance was indicated by p < 0.05 and 95 % confidence intervals ( CI ) . Results . Among the 10,682 women with GDM who required medical therapy and met study criteria , 2073 ( 19.4 % ) received glyburide and 8609 ( 80.6 % ) received subcutaneous insulin injections . Compared to insulin therapy and controlling for confounders , oral hypoglycemic treatment was associated with increased risk of birthweight > 4000 g ( aOR = 1.29 ; 95 % CI [ 1.03–1.64 ] ) , and admission to the intensive care nursery ( aOR = 1.46 [ 1.07–2.00 ] ) . Conclusion . Neonates born to women with gestational diabetes managed on glyburide , and were more likely to be macrosomic and to be admitted to the intensive care unit compared to those treated with insulin injections . These findings should be examined in a large , prospect i ve trial Context Metformin is used in pregnancy in women with gestational diabetes mellitus , polycystic ovary syndrome ( PCOS ) , and obesity .  Metformin passes the placenta . Objective To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age . Design Follow-up study of two r and omized , double-blind , placebo-controlled trials . Setting Secondary care centers . Eleven public hospitals in Norway . Participants One hundred eighty-two children of mothers with PCOS who participated in two r and omized controlled trials . Intervention Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies . No intervention in the current study . Main Outcome Measures Height , weight , body mass index ( BMI ) , and overweight/obesity at 4 years of age and head circumference at 1 year of age , converted to z scores . Results The difference in height z score means between the groups at 4 years of age was nonsignificant ( 0.07 [ 95 % confidence interval ( CI ) : -0.22 to 0.36 ] ; P = 0.651 ) . At 4 years of age , the metformin group had higher weight z score than the placebo group [ difference in means : 0.38 ( 0.07 to 0.69 ) ; P = 0.017 ] and higher BMI z score [ difference in means : 0.45 ( 0.11 to 0.78 ) ; P = 0.010 ] . There were more overweight/obese children in the metformin group [ 26 ( 32 % ) ] than in the placebo group [ 14 ( 18 % ) ] at 4 years of age [ odds ratio : 2.17 ( 1.04 to 4.61 ) ; P = 0.038 ] . The difference in mean head circumference z score at 1 year of age was 0.27 ( -0.04 to 0.58 ; P = 0.093 ) . Conclusion Metformin-exposed  children had higher BMI and increased prevalence of overweight/obesity at 4 years of age The  pregnancy  outcome of 33 women with gestational diabetes who were treated with glibenclamide and changed to insulin if glibenclamide failed , were compared with the pregnancy outcome of 21 women with gestational diabetes treated conventionally with insulin .  The pregnancy outcome , with regard to the overall glycaemic control , rates of preterm labour , neonatal hypoglycaemia , fetal macrosomia , perinatal morbidity and mortality , were not statistically different between the two treatment groups . The limited number of women studied , and the non-r and om allocation of these women to each treatment group however , could have influenced these results . There were a few observed differences in the pregnancy outcome between the two treatment groups , which although were not statistically significant , caused some concern . In particular we noted an increased rate of fetal macrosomia in the glibenclamide treated group , which in theory could have been drug mediated Insulin is currently the drug of choice in treating patients with gestational diabetes mellitus but insulin is expensive , inconvenient to store and use and probably associated with more risks of asymptomatic hypoglycemia in comparison with some oral agents . This r and omized clinical trial was conducted to evaluate the efficacy and safety of glyburide in patients with gestational diabetes mellitus in comparison with insulin therapy .  Pregnant women aged between 18 - 45 years with singleton pregnancies and in their 24 - 36 weeks of gestation were assessed for eligibility . Women with gestational diabetes mellitus were r and omly allocated to two insulin and glyburide groups and compared with maternal and neonatal outcome . Ninety-six women with gestational diabetes mellitus enrolled in the study . At screen and treated fasting and post-pr and ial blood glucose levels were similar in both groups . Time for beginning the treatment to control the glycemic index was 28.30 ( ±20.60 ) days in the insulin group and 22.56 ( ±18.86 ) in the glyburide group . There was no statistically significant difference in time-to-control the blood glucose level in two studied group . Time , between beginning the treatment of GDM and delivery , was 53.22 ( ±28.96 ) days in the insulin group and 56.67 ( ±30.47 ) in the glyburide group . There was no statistically significant difference between the times of treatment-to-delivery in two studied groups . There were no statistically significant differences between maternal and neonatal outcomes in two studied groups . Glyburide  can effectively and safely control the glycemic index in women with gestational diabetes mellitus in comparison with insulin Importance R and omized trials have not focused on neonatal complications of glyburide for women with gestational diabetes . Objective To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes . Design , Setting s , and Participants The Insulin Daonil trial ( INDAO ) , a multicenter noninferiority r and omized trial conducted between May 2012 and November 2016 ( end of participant follow-up ) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation . Interventions Women who required pharmacologic treatment after 10 days of dietary intervention were r and omly assigned to receive glyburide ( n=460 ) or insulin ( n=454 ) . The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses , up to a maximum of 20 mg/d . The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations . Main Outcomes and Measures The primary outcome was a composite criterion including macrosomia , neonatal hypoglycemia , and hyperbilirubinemia . The noninferiority margin was set at 7 % based on a 1-sided 97.5 % confidence interval . Results Among the 914 patients who were r and omized ( mean age , 32.8 [ SD , 5.2 ] years ) , 98 % completed the trial . In a per- protocol analysis , 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups , respectively . The frequency of the primary outcome was 27.6 % in the glyburide group and 23.4 % in the insulin group , a difference of 4.2 % ( 1-sided 97.5 % CI , −∞ to 10.5 % ; P=.19 ) . Conclusion and Relevance This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications . These findings do not justify the use of glyburide as a first-line treatment . Trial Registration clinical trials.gov Identifier : BACKGROUND Metformin is a logical treatment for women with gestational diabetes mellitus , but r and omized trials to assess the efficacy and safety of its use for this condition are lacking . METHODS We r and omly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin ( with supplemental insulin if required ) or insulin . The primary outcome was a composite of neonatal hypoglycemia , respiratory distress , need for phototherapy , birth trauma , 5-minute Apgar score less than 7 , or prematurity . The trial was design ed to rule out a 33 % increase ( from 30 % to 40 % ) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin . Secondary outcomes included neonatal anthropometric measurements , maternal glycemic control , maternal hypertensive complications , postpartum glucose tolerance , and acceptability of treatment . RESULTS Of the 363 women assigned to metformin  , 92.6 % continued to receive metformin until delivery and 46.3 % received supplemental insulin . The rate of the primary composite outcome was 32.0 % in the group assigned to metformin and 32.2 % in the insulin group ( relative risk , 0.99 [ corrected ] ; 95 % confidence interval , 0.80 [ corrected ] to 1.23 [ corrected ] ) . More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again ( 76.6 % vs. 27.2 % , P<0.001 ) . The rates of other secondary outcomes did not differ significantly between the groups . There were no serious adverse events associated with the use of metformin . CONCLUSIONS In women with gestational diabetes mellitus , metformin ( alone or with supplemental insulin ) is not associated with increased perinatal complications as compared with insulin . The women preferred metformin to insulin treatment . ( Australian New Zeal and Clinical Trials Registry number , 12605000311651 . ) OBJECTIVE : To estimate the magnitude of transplacental transfer of glyburide in women with gestational diabetes mellitus ( GDM ) . METHODS : A prospect i ve , observational study was conducted on women with GDM on glyburide therapy .  On delivery admission , the glyburide dose and time of last dose were recorded . Immediately postdelivery , maternal and umbilical venous blood sample s were obtained and the concentrations of glyburide were determined by high-performance liquid chromatography – mass spectrometry with a limit of detection of 0.25 ng/mL. RESULTS : Nineteen patient dyads were analyzed . The mean total daily maternal glyburide dose was 6.6±6.3 mg per day and the mean time between last dose and sampling was 13.3±6.5 hours . The mean maternal serum glyburide level at birth was 15.4±20.8 ng/mL , whereas the mean umbilical glyburide level was 7.5±8.2 ng/mL , which showed a statistical correlation ( r 2=0.72 , P<.01 ) . There were statistically significant relationships between total maternal glyburide dose ( 1.25–20 mg per day ) and maternal glyburide levels ( 0.93–70.71 ng/mL ; r 2=0.46 , P⩽.01 ) and between total maternal glyburide dose and umbilical glyburide levels ( 0.95–32.41 ng/mL ; r 2=0.43 , P⩽.01 ) However , we observed wide variability in maternal and umbilical glyburide levels at both extremes of the total glyburide dose . Seventy-nine percent of cord sample s ( 15/19 ) had glyburide levels less than 10 ng/mL ( the limit of detection reported in earlier studies ) and 37 % ( 7/19 ) were higher than the corresponding maternal sample s. CONCLUSION : Transplacental transfer of glyburide is highly variable among patients , corroborating ex vivo placental perfusion studies showing a transport-mediated glyburide efflux from the fetal to the maternal circulation . In most neonates ( 79 % ) , glyburide levels were below 10 ng/mL. LEVEL OF EVIDENCE : OBJECTIVE We hypothesized that body composition would be similar among neonates of women with gestational diabetes ( GDM ) treated with glyburide or insulin . STUDY DESIGN Women with GDM requiring medical therapy were r and omized to insulin or glyburide . The primary outcome was percent neonatal fat mass measured by total body electrical conductivity . Secondary outcomes included anthropometrics , glycemic control , and biomarkers . Statistical analysis included Student t test , chi(2 ) , and regression modeling . RESULTS Eighty-two neonates underwent postnatal measurements . Baseline factors were not different by group . Neonatal percent fat mass did not differ between treatment groups ( 11.2 + /- 4.2 vs 12.8 + /- 5.7 ) . Fat mass , body mass index , ponderal index , skinfold sum , and arm fat area were not different when analyzed by intent to treat or actual treatment group . Cord concentrations of biomarkers were also similar . CONCLUSION There was no difference in neonatal adiposity in infants of women treated for GDM with glyburide or insulin Abstract Aim : To evaluate the safety , efficacy and pregnancy outcomes of insulin detemir ( IDet ) versus glyburide treatment in women with gestational diabetes mellitus ( GDM ) . Methods : We conducted a retrospective cohort study of women with GDM who were treated with either glyburide or IDet for GDM in a university-affiliated tertiary hospital . Results : Ninety-one patients with GDM were enrolled , 62 were administered glyburide and 29 IDet .  Maternal age , pregestational body mass index ( BMI ) and rate of abnormal oral glucose tolerance test ( OGTT ) blood glucose values were not significantly different between groups . Good glycemic control rates were comparable . Hypoglycemic episodes were reported only in the glyburide group ( 19.4 % versus 0 % , p = 0.01 ) . Maternal weight gain during pregnancy was significantly higher among women in the glyburide group ( 8.8 ± 5.1 kg , p < 0.001 ) compared to those in the IDet group ( 2.1 ± 19.9 kg , p = 0.71 ) . Conclusions : To the best of our knowledge , this is the first study on IDet treatment in patients with GDM . By our preliminary results , IDet is a viable treatment option in women with GDM . Further large prospect i ve studies are needed to determine the efficacy and safety of IDet in GDM patients Objective To compare the use of glyburide and insulin in the treatment of gestational diabetes . Design R and omized controlled trial . Setting Maternal health clinics in San Antonio , Texas . Patients Women with mild gestational diabetes ( n = 404 ) at 11 - 33 weeks gestation . Only women with a singleton pregnancy were eligible . Intervention Glyburide ( starting dose 2.5 mg , increased as necessary to achieve target glycaemic control to a maximum of 20 mg ) or insulin ( 0.7 U per kg body weight , three times daily , increased as necessary ) . If blood glucose goals were not met after 2 weeks of treatment with the maximal dose of glyburide , treatment was switched to insulin . Main outcome measures Primary outcome was achievement of a desirable level of glycaemic control ( strict target ranges were set for mean , fasting , prepr and ial and postpr and ial blood glucose , measured by frequent home monitoring ) . Neonatal outcomes were also assessed . Main results Eighty-two percent of women in the glyburide group and 88 % of women in the insulin group achieved the target blood glucose values ( difference = -6 % , 95 % confidence interval ( CI ) -13 % to + 1 % , P = 0.07 ) . Considerably less women in the glyburide group had blood glucose values below 40 mg ( 2.2 mmol/l ) per decilitre ( 2 % vs. 20 % , difference -18 % , 95 % CI -24 % to -13 % , P < 0.0001 ) . In the glyburide group , 4 % of women were switched to insulin as the maximal dose failed to produce target blood glucose values . There were no significant differences in neonatal outcomes , including cord serum insulin . Conclusion Treatment of women with gestational diabetes , after the first trimester of pregnancy , with glyburide rather than insulin can achieve similar glycaemic control , with less hypoglycaemia Glyburide 's pharmacokinetics ( PK ) and pharmacodynamics have not been studied in women with gestational diabetes mellitus ( GDM ) . The objective of this study was to assess steady‐state PK of glyburide  , as well as insulin sensitivity , β‐cell responsivity , and overall disposition indices after a mixed‐meal tolerance test ( MMTT ) in women with GDM ( n = 40 ) , nonpregnant women with type 2 diabetes mellitus ( T2DM ) ( n = 26 ) , and healthy pregnant women ( n = 40 , MMTT only ) . At equivalent doses , glyburide plasma concentrations were ~50 % lower in pregnant women than in nonpregnant subjects . The average umbilical cord/maternal plasma glyburide concentration ratio at the time of delivery was 0.7 ± 0.4 . Insulin sensitivity was approximately fivefold lower in women with GDM as compared with healthy pregnant women . Despite comparable β‐cell responsivity indices , the average β‐cell function corrected for insulin resistance was more than 3.5‐fold lower in women with glyburide‐treated GDM than in healthy pregnant women . Women with GDM in whom glyburide treatment has failed may benefit from alternative medication or dosage escalation ; however , fetal safety should be kept in mind OBJECTIVES Equivalent efficacy of glyburide and insulin for treatment of gestational diabetes ( GDM ) was demonstrated in a recent r and omized trial . We describe our experience with glyburide in practice , and suggest factors that predict failure of glyburide treatment . METHODS Women with GDM treated with glyburide were studied . They were divided into two groups : those who achieved adequate glycemic control with glyburide , and those who did not . The groups were compared in terms of baseline characteristics , including diabetes risk factors and glucose testing values . Receiver operating characteristics ( ROC ) curves were generated to identify thresholds for fasting plasma glucose and body mass index ( BMI ) that would predict glyburide failure . RESULTS Seventy-five women were analyzed : 63 ( 84 % ) were successfully treated with glyburide , and 12 ( 16 % ) were not . Baseline characteristics were similar between the groups , except that failures had higher 3-h glucose tolerance test ( GTT ) values at all time points . ROC curves for fasting plasma glucose , pre-pregnancy BMI and BMI at diagnosis revealed no cut-off points for predicting failure of glyburide therapy . However , when fasting plasma glucose value on the GTT was > or = 110 mg/dl , 24 % of women failed to respond to glyburide , compared to 12 % at < 110 mg/dl ( p = 0.15 ) . CONCLUSIONS In treatment of GDM , glyburide is successful in achieving good glycemic control in most women . Women with high fasting plasma glucose levels , however , may not respond adequately to glyburide therapy Use of oral agents to treat gestational diabetes mellitus remains controversial . Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide . However , several issues should give pause to the widespread adoption of metformin use during pregnancy . Fetal concentrations of metformin are equal to maternal , and metformin can inhibit growth , suppress mitochondrial respiration , have epigenetic modifications on gene expression , mimic fetal nutrient restriction , and alter postnatal gluconeogenic responses . Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity , these properties raise important questions about developmental programming of metabolic disease in offspring . Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism . Two recent clinical r and omized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity . These developmental programming effects challenge the conclusion that metformin is equivalent to insulin . Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used , there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide . Moreover , it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties , result ing in poor glycemic control and high rates of maternal hypoglycemia . We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists , which recommend insulin as the preferred agent , but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide . Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide , we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy , appropriately target medications based on individual patterns of hyperglycemia , and follow the offspring long-term for metabolic risk The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on research gaps in gestational diabetes mellitus ( GDM ) with a focus on 1 ) early pregnancy diagnosis and treatment and 2 ) pharmacologic treatment strategies . This article summarizes the proceedings of the workshop . In early pregnancy , the appropriate diagnostic criteria for the diagnosis of GDM remain poorly defined , and an effect of early diagnosis and treatment on the risk of adverse outcomes has not been demonstrated . Despite many small r and omized controlled trials of glucose-lowering medication treatment in GDM , our underst and ing of medication management of GDM is incomplete as evidence d by discrepancies among professional society treatment guidelines . The comparative effectiveness of insulin , metformin , and glyburide remains uncertain , particularly with respect to long-term outcomes . Additional topics in need of further research identified by workshop participants included phenotypic heterogeneity in GDM and novel and individualized treatment approaches . Further research on these topics is likely to improve our underst and ing of the pathophysiology and treatment of GDM to improve both short- and long-term outcomes for mothers and their children AIM The aim of this study was to assess the efficacy of glyburide in the treatment of gestational diabetes mellitus and to compare the maternal and fetal outcome between two groups treated either with insulin or glyburide . MATERIAL AND METHODS Women with gestational diabetes not responding to diet control were r and omized into two groups : ( i ) the control group receiving insulin ( n = 32 ) ; and ( ii ) the study group receiving glyburide ( n = 32 ) . Primary outcome was assessed in terms of achievement of glycemic control and secondary outcome was assessed by the incidence of maternal and fetal complications in the insulin and glyburide treated groups . RESULTS The achievement of glycemic control between the insulin and the glyburide treated groups showed no significant difference ( 97.1 % , 93.8 % ) . The occurrence of maternal complications ( P = 0.87 ) and fetal complications ( P = 0.32 ) were comparable between the insulin and glyburide treated groups . CONCLUSION Glyburide was found to be as efficacious as insulin in achieving euglycemia in the treatment of gestational diabetic women who require treatment beyond diet control
To obtain precise findings from published studies about the efficacy and safety of glyburide versus subcutaneous insulin in patients with gestational diabetes mellitus ( GDM ) .