Metformin Treatment in Type 2 Diabetes in Pregnancy: An Active Controlled, Parallel-Group, Randomized, Open Label Study in Patients with Type 2 Diabetes in Pregnancy Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study. Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital: A Randomized Clinical Trial A pilot randomized, controlled trial of metformin versus insulin in women with type 2 diabetes mellitus during pregnancy. Homocysteine levels are unaffected by metformin treatment in both nonpregnant and pregnant women with polycystic ovary syndrome Glycemia and Its Relationship to Outcomes in the Metformin in Gestational Diabetes Trial Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group. Metformin and insulin in the management of gestational diabetes mellitus: preliminary results of a comparison. Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU) Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. Metformin in women with type 2 diabetes in pregnancy (MiTy): a multi-center randomized controlled trial Metformin versus insulin for the treatment of gestational diabetes. Height, weight, and motor-social development during the first 18 months of life in 126 infants born to 109 mothers with polycystic ovary syndrome who conceived on and continued metformin through pregnancy. A Trial in Progress: Gestational Diabetes Efficacy of metformin versus insulin in the management of pregnancy with diabetes. Placental transfer of rosiglitazone in the first trimester of human pregnancy. The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial Comparison of neonatal outcomes in women with gestational diabetes with moderate hyperglycaemia on metformin or glibenclamide – A randomised controlled trial Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program Metformin compared with insulin in the management of gestational diabetes mellitus: a randomized clinical trial. Metformin treatment in pregnant women with polycystic ovary syndrome--is reduced complication rate mediated by changes in the uteroplacental circulation? Perfusion studies of glyburide transfer across the human placenta: implications for fetal safety. Glyburide in Women With Mild Gestational Diabetes: A Randomized Controlled Trial Metformin compared with insulin in the treatment of pregnant women with overt diabetes: a randomized controlled trial. A comparison of glyburide and insulin in women with gestational diabetes mellitus. A multicenter, randomized trial of treatment for mild gestational diabetes. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Women's views on postpartum testing for type 2 diabetes after gestational diabetes: Six month follow-up to the DIAMIND randomised controlled trial.
Aims . To assess the effect of metformin and to compare it with insulin treatment in patients with type 2 diabetes in pregnancy in terms of perinatal outcome , maternal complications , additional insulin requirement , and treatment acceptability . Methods . In this r and omized , open label study , 206 patients with type 2 diabetes in pregnancy who met the eligibility criteria were selected from the antenatal clinics .  Insulin was added to metformin treatment when required , to maintain the target glycemic control . The patients were followed up till delivery . Maternal , and perinatal outcomes and pharmacotherapeutic characteristics were recorded on a proforma . Results . Maternal characteristics were comparable in metformin and insulin treated group . 84.9 % patients in metformin group required add-on insulin therapy at mean gestational age of 26.58 ± 3.85 weeks . Less maternal weight gain ( P < 0.001 ) and pregnancy induced hypertension ( P = 0.029 ) were observed in metformin treated group . Small for date babies were more in metformin group ( P < 0.01 ) . Neonatal hypoglycemia was significantly less and so was NICU stay of > 24 hours in metformin group ( P < 0.01 ) . Significant reduction in cost of treatment was found in metformin group . Conclusion . Metformin alone or with add-on insulin is an effective and cheap treatment option for patients with type 2 diabetes in pregnancy . This trial is registered with clinical trial registration number : Clinical trials.gov NCT01855763 BACKGROUND Investigation of a possible effect of metformin on and rogen levels in pregnant women with polycystic ovary syndrome ( PCOS ) . METHODS A prospect i ve , r and omized , double-blind , placebo-controlled pilot study was conducted . Forty pregnant women with PCOS received diet and lifestyle counselling  and were r and omized to either metformin 850 mg twice daily or placebo . Primary outcome measures were changes in serum levels of dehydroepi and rosterone sulphate , and rostenedione , testosterone , sex hormone-binding globulin , and free testosterone index . Secondary outcome measures were pregnancy complications and outcome . Two-tailed t-tests and chi2-tests were used . RESULTS Maternal and rogen levels were unaffected by metformin treatment in pregnant women with PCOS . While none of the 18 women in the metformin group experienced a severe pregnancy or post-partum complication , seven of the 22 ( 32 % ) women experienced severe complications in the placebo group ( P = 0.01 ) . CONCLUSIONS Metformin treatment did not reduce maternal and rogen levels in pregnant women with PCOS . In the metformin-treated group we observed a reduction of severe , pregnancy and post-partum complications .  Metformin treatment of pregnant PCOS women may reduce complications during pregnancy and in the post-partum period Objective To determine if metformin monotherapy or metformin in combination with insulin is equally effective as insulin monotherapy at glycemic control in diabetes mellitus in pregnancy among Ghanaians . Methods This was a study involving 104 pregnant women with type 2 diabetes mellitus ( T2DM ) or gestational diabetes mellitus ( GDM ) at 20 - 30 weeks gestation . Participants were r and omized into metformin and insulin treatment groups . Starting dose of metformin was 500 mg once a day and increased gradually over two ( 2 ) weeks , to meet glycemic targets . Insulin was added if targets could not be reached on metformin alone at maximum doses . Total daily dose of premixed insulin at initiation was calculated as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control . Glycemic profile monitoring was done every two weeks . Results The two hour post pr and ial blood glucose ( 2HPG ) levels were significantly lower in the metformin group than the insulin group ( p= 0.004 ) . Conclusion The findings of this study suggest that metformin monotherapy is effective in achieving glycemic targets in the management of diabetes in pregnancy . It is more effective than insulin in lowering the 2HPG level . Trial Registration Australian New Zeal and Clinical Trials Registry ( ANZCTR ) OBJECTIVE Few studies support oral diabetic treatment in pregnant women with type 2 diabetes mellitus ( T2DM ) . The objective of this study was to compare the effects of metformin versus insulin on achieving glycemic control and improving maternal and neonatal outcomes in pregnant women with T2DM . STUDY DESIGN A pilot r and omized , controlled trial was conducted of metformin versus insulin for the treatment of T2DM during pregnancy . The primary outcome was glycemic control measured with hemoglobin A1c < 7 % at delivery . Maternal and neonatal outcomes were compared between groups . RESULTS In this study , 8 women received metformin and 11 received insulin .  All women in both groups achieved glycemic control by delivery ( HgbA1c : metformin 5.96 ± 5.88 vs. insulin 6.34 ± 0.92 % ) . There were similar rates of cesarean delivery , birth weights , neonatal intensive care unit admissions , respiratory distress syndrome , and neonatal dextrose treatment between groups . There was one case of fetal macrosomia in the insulin group , one case of shoulder dystocia in the metformin group and no cases of failed metformin therapy . CONCLUSION In this pilot study , glycemic control was achieved in women who received metformin and insulin . Larger studies are needed to determine whether metformin can be considered a reasonable alternative to insulin in pregnant women with T2DM Background . Women with polycystic ovary syndrome have elevated homocysteine levels . Elevated homocysteine levels associate with pregnancy complications . Women with polycystic ovary syndrome are often treated with metformin , a drug that may increase homocysteine levels . Hence , we investigated the effect of metformin treatment on homocysteine levels in nonpregnant and pregnant women with polycystic ovary syndrome . Methods . Two prospect i ve r and omized placebo‐controlled studies included women with polycystic ovary syndrome in a university hospital setting . Sixty‐three infertile women were treated with metformin 1,000 mg bid or placebo for 16 weeks and 38 pregnant women with metformin 850 mg bid or placebo from the first trimester and throughout pregnancy . All the women had polycystic ovary syndrome and all participants received diet and lifestyle advice , and oral folate and vitamin B12 substitution , and a daily oral multivitamin tablet . The main outcome measures were serum levels of homocysteine , folate , and vitamin B12 . Results . Serum homocysteine levels were unaffected by metformin treatment both in nonpregnant and pregnant women with polycystic ovary syndrome . However , in nonpregnant women both serum folate and vitamin B12 levels decreased with treatment . At inclusion in nonpregnant women , serum homocysteine levels associated negatively with serum levels of folate and methyl malonic acid and positively with free testosterone index . No such associations were seen in pregnant women . Conclusions . Metformin treatment in women with polycystic ovary does not increase serum homocysteine levels in the nonpregnant or the pregnant state OBJECTIVE To determine how glucose control in women with GDM treated with metformin and /or insulin  influenced  pregnancy outcomes . RESEARCH DESIGN AND METHODS Women r and omly assigned to metformin or insulin treatment in the Metformin in Gestational Diabetes ( MiG ) trial had baseline glucose tolerance test ( OGTT ) results and A1C documented , together with all capillary glucose measurements during treatment . In the 724 women who had glucose data for analysis , tertiles of baseline glucose values and A1C and of mean capillary glucose values during treatment were calculated . The relationships between maternal factors , glucose values , and outcomes ( including a composite of neonatal complications , preeclampsia , and large-for-gestational-age [ LGA ] and small-for-gestational-age infants ) were examined with bivariable and multivariate models . RESULTS Baseline OGTT did not predict outcomes , but A1C predicted LGA infants ( P = 0.003 ) . During treatment , fasting capillary glucose predicted neonatal complications ( P < 0.001 ) and postpr and ial glucose predicted preeclampsia ( P = 0.016 ) and LGA infants ( P = 0.001 ) . Obesity did not influence outcomes , and there was no interaction between glycemic control , r and omized treatment , or maternal BMI in predicting outcomes . The lowest risk of complications was seen when fasting capillary glucose was < 4.9 mmol/l ( mean ± SD 4.6 ± 0.3 mmol/l ) compared with 4.9–5.3 mmol/l or higher and when 2-h postpr and ial glucose was 5.9–6.4 mmol/l ( 6.2 ± 0.2 mmol/l ) or lower . CONCLUSIONS Glucose control in women with gestational diabetes mellitus treated with metformin and /or insulin is strongly related to outcomes . Obesity is not related to outcomes in this group . Targets for fasting and postpr and ial capillary glucose may need to be lower than currently recommended BACKGROUND We conducted a r and omized clinical trial to determine whether treatment of women with gestational diabetes mellitus reduced the risk of perinatal complications . METHODS We r and omly assigned women between 24 and 34 weeks ' gestation who had gestational diabetes to receive dietary advice , blood glucose monitoring , and insulin therapy as needed ( the intervention group ) or routine care . Primary outcomes included serious perinatal complications ( defined as death , shoulder dystocia , bone fracture , and nerve palsy ) , admission to the neonatal nursery , jaundice requiring phototherapy , induction of labor , cesarean birth , and maternal anxiety , depression , and health status . RESULTS The rate of serious perinatal complications was significantly lower among the infants of the 490 women in the intervention group than among the infants of the 510 women in the routine-care group ( 1 percent vs. 4 percent ; relative risk adjusted for maternal age , race or ethnic group , and parity , 0.33 ; 95 percent confidence interval , 0.14 to 0.75 ; P=0.01 ) . However , more infants of women in the intervention group were admitted to the neonatal nursery ( 71 percent vs. 61 percent ; adjusted relative risk , 1.13 ; 95 percent confidence interval , 1.03 to 1.23 ; P=0.01 ) . Women in the intervention group had a higher rate of induction of labor than the women in the routine-care group ( 39 percent vs. 29 percent ; adjusted relative risk , 1.36 ; 95 percent confidence interval , 1.15 to 1.62 ; P<0.001 ) , although the rates of cesarean delivery were similar ( 31 percent and 32 percent , respectively ; adjusted relative risk , 0.97 ; 95 percent confidence interval , 0.81 to 1.16 ; P=0.73 ) . At three months post partum , data on the women 's mood and quality of life , available for 573 women , revealed lower rates of depression and higher scores , consistent with improved health status , in the intervention group . CONCLUSIONS Treatment of gestational diabetes reduces serious perinatal morbidity and may also improve the woman 's health-related quality of life BACKGROUND Sulfonylurea drugs have been the only oral therapy available for patients with non-insulin-dependent diabetes mellitus ( NIDDM ) in the United States . Recently , however , metformin has been approved for the treatment of NIDDM . METHODS We performed two large , r and omized , parallel-group , double-blind , controlled studies in which metformin or another treatment was given for 29 weeks to moderately obese patients with NIDDM whose diabetes was inadequately controlled by diet ( protocol 1 : metformin vs. placebo ; 289 patients ) , or diet plus glyburide ( protocol 2 :  metformin and glyburide vs. metformin vs. glyburide  ; 632 patients ) . To determine efficacy we measured plasma glucose ( while the patients were fasting and after the oral administration of glucose ) , lactate , lipids , insulin , and glycosylated hemoglobin before , during , and at the end of the study . RESULTS In protocol 1 , at the end of the study the 143 patients in the metformin group , as compared with the 146 patients in the placebo group , had lower mean ( + /- SE ) fasting plasma glucose concentrations ( 189 + /- 5 vs. 244 + /- 6 mg per deciliter [ 10.6 + /- 0.3 vs. 13.7 + /- 0.3 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.6 + /- 0.2 percent , P < 0.001 ) . In protocol 2 , the 213 patients given metformin and glyburide , as compared with the 210 patients treated with glyburide alone , had lower mean fasting plasma glucose concentrations ( 187 + /- 4 vs. 261 + /- 4 mg per deciliter [ 10.5 + /- 0.2 vs. 14.6 + /- 0.2 mmol per liter ] , P < 0.001 ) and glycosylated hemoglobin values ( 7.1 + /- 0.1 percent vs. 8.7 + /- 0.1 percent , P < 0.001 ) . The effect of metformin alone was similar to that of glyburide alone . Eighteen percent of the patients given metformin and glyburide had symptoms compatible with hypoglycemia , as compared with 3 percent in the glyburide group and 2 percent in the metformin group . In both protocol s the patients given metformin had statistically significant decreases in plasma total and low-density lipoprotein cholesterol and triglyceride concentrations , whereas the values in the respective control groups did not change . There were no significant changes in fasting plasma lactate concentrations in any of the groups . CONCLUSIONS Metformin monotherapy and combination therapy with metformin and sulfonylurea are well tolerated and improve glycemic control and lipid concentrations in patients with NIDDM whose diabetes is poorly controlled with diet or sulfonylurea therapy alone OBJECTIVE To compare glycemic control and neonatal outcomes in women with gestational diabetes mellitus ( GDM ) treated with metformin vs. insulin . STUDY DESIGN Women with GDM not controlled with diet and exercise were r and omized to metformin ( n = 32 ) or insulin ( n = 31 ) . The levels of glycemic control as well as maternal/neonatal complications were evaluated . RESULTS The mean ( + /- SD ) fasting and 2-hour postpr and ial blood glucose did not differ statistically between the 2 treatment groups . No patient failed metformin and required insulin . The majority ( 27/32 ) were easily controlled on the initial dosage ( 500 mg twice a day ) . Gestational age at entry and delivery ( p = 0.077 , 0.412 ) were similar . The difference in the rate of cesarean delivery was not statistically significant between the 2 groups ( p = 0.102 ) . Neonatal statistics were also not different between the metformin and insulin groups : birth weight , Apgar score at 5 minutes , respiratory distress syndrome , hyperbilirubinemia , neonatal hypoglycemia and neonatal intensive care unit admission ( p = 0.144 - 0.373 ) . CONCLUSION Based on these preliminary data , metformin appears to be an effective alternative to insulin in the treatment of GDM OBJECTIVE In women with gestational diabetes mellitus , who were r and omized to metformin or insulin treatment , pregnancy outcomes were similar ( Metformin in Gestational diabetes [ MiG ] trial ) . Metformin crosses the placenta , so it is important to assess potential effects on growth of the children . RESEARCH DESIGN AND METHODS In Auckl and , New Zeal and , and Adelaide , Australia , women who had participated in the MiG trial were review ed when their children were 2 years old .  Body composition was measured in 154 and 164 children whose mothers had been r and omized to metformin and insulin , respectively . Children were assessed with anthropometry , bioimpedance , and dual energy X-ray absorptiometry ( DEXA ) , using st and ard methods . RESULTS The children were similar for baseline maternal characteristics and pregnancy outcomes . In the metformin group , compared with the insulin group , children had larger mid-upper arm circumferences ( 17.2 ± 1.5 vs. 16.7 ± 1.5 cm ; P = 0.002 ) and subscapular ( 6.3 ± 1.9 vs. 6.0 ± 1.7 mm ; P = 0.02 ) and biceps skinfolds ( 6.03 ± 1.9 vs. 5.6 ± 1.7 mm ; P = 0.04 ) . Total fat mass and percentage body fat assessed by bioimpedance ( n = 221 ) and DEXA ( n = 114 ) were not different . CONCLUSIONS Children exposed to metformin had larger measures of subcutaneous fat , but overall body fat was the same as in children whose mothers were treated with insulin alone . Further follow-up is required to examine whether these findings persist into later life and whether children exposed to metformin will develop less visceral fat and be more insulin sensitive . If so , this would have significant implication s for the current p and emic of diabetes OBJECTIVE We sought to investigate the association between glyburide dose , degree of severity in  gestational diabetes mellitus ( GDM ) ,  level of glycemic control , and  pregnancy outcome in insulin- and glyburide-treated patients . STUDY DESIGN In a secondary analysis of our previous r and omized study , 404 women were analyzed . The association among glyburide dose , severity of GDM , and selected maternal and neonatal factors was evaluated . Severity levels of GDM were stratified by fasting plasma glucose ( FPG ) from the oral glucose tolerance test ( OGTT ) . Infants with birth weight at or above the 90th percentile were considered large-for-gestational age ( LGA ) . Macrosomia was defined as birth weight > or = 4000 g. Well-controlled was defined as mean blood glucose < or = 95 mg/dL. The association between glyburide- and insulin-treated patients by severity of GDM and neonatal outcome was evaluated . RESULTS The dose received for the glyburide-treated patients was 2.5 mg-32 % ; 5 mg-23 % ; 10 mg-17 % ; 15 mg-8 % ; and 20 mg-20 % . Patients were grouped into low ( < or = 10 mg ) and high ( > 10 mg ) daily dose of glyburide . A comparison between severity of the disease ( fasting plasma glucose categories ) and highest dose of glyburide revealed a significant difference between the low-95 FPG and the other severity categories ( P = .02 ) . Of patients in the well-controlled glycemic group , only 6 % required the high dose of glyburide ( > 10 mg ) . In patients with poor glycemic control ( mean blood glucose > 95 mg/dL ) , 38 % received the high dose of glyburide ( P = .0001 ) . Comparison between the high glyburide ( > 10 mg ) and the low glyburide dosages ( < or = 10 mg ) revealed that the rate of macrosomia was 16 % vs 5 % and LGA 22 % vs 8 % , ( P = .01 ) , respectively . No significant difference was found in composite outcome , metabolic complications , and Ponderal Index between the 2 dose groups . Stratification by disease severity revealed a significantly lower rate of LGA for both the glyburide- and insulin-treated subjects . No significant difference was found between metabolic , respiratory , and neonatal intensive care unit ( NICU ) for patients within each fasting plasma glucose severity category . CONCLUSION Glyburide and insulin are equally efficient for treatment of GDM in all levels of disease severity . Achieving the established level of glycemic control , not the mode of pharmacologic therapy , is the key to improving the outcome in GDM Background The incidence of type 2 diabetes in pregnancy is rising and rates of serious adverse maternal and fetal outcomes remain high . Metformin is a biguanide that is used as first-line treatment for non-pregnant patients with type 2 diabetes . We hypothesize that metformin use in pregnancy , as an adjunct to insulin , will decrease adverse outcomes by reducing maternal hyperglycemia , maternal insulin doses , maternal weight gain and gestational hypertension/pre-eclampsia . In addition , since metformin crosses the placenta , metformin treatment of the fetus may have a direct beneficial effect on neonatal outcomes . Our aim is to compare the effectiveness of the addition of metformin to insulin , to st and ard care ( insulin plus placebo ) in women with type 2 diabetes in pregnancy . Methods The MiTy trial is a multi-centre r and omized trial currently enrolling pregnant women with type 2 diabetes , who are on insulin , between the ages of 18–45 , with a gestational age of 6 weeks 0 days to 22 weeks 6 days . In this r and omized , double-masked , parallel placebo-controlled trial , after giving informed consent , women are r and omized to receive either metformin 1,000 mg twice daily or placebo twice daily . A web-based block r and omization system is used to assign women to metformin or placebo in a 1:1 ratio , stratified for site and body mass index . The primary outcome is a composite neonatal outcome of pregnancy loss , preterm birth , birth injury , moderate/severe respiratory distress , neonatal hypoglycemia , or neonatal intensive care unit admission longer than 24 h. Secondary outcomes are large for gestational age , cord blood gas pH < 7.0 , congenital anomalies , hyperbilirubinemia , sepsis , hyperinsulinemia , shoulder dystocia , fetal fat mass , as well as maternal outcomes : maternal weight gain , maternal insulin doses , maternal glycemic control , maternal hypoglycemia , gestational hypertension , preeclampsia , cesarean section , number of hospitalizations during pregnancy , and duration of hospital stays . The trial aims to enroll 500 participants . Discussion The results of this trial will inform endocrinologists , obstetricians , family doctors , and other healthcare professionals caring for women with type 2 diabetes in pregnancy , as to the benefits of adding metformin to insulin in this high risk population .Trial registration Clinical Trials.gov Identifier : no. NCT01353391 . Registered February 6 , 2009 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 . ) BACKGROUND We prospect ively assessed growth and motor-social development during the first 18 months of life in 126 live births ( 122 pregnancies ) to 109 women with polycystic ovary syndrome ( PCOS ) who conceived on and continued metformin ( 1.5 - 2.55 g/day ) through pregnancy . METHODS The lengths and weights of PCOS neonates were compared with gender-specific Centers for Disease Control and Prevention ( CDC ) infant data . Gestational diabetes ( GD ) and pre-eclampsia in women with PCOS were compared with 252 healthy women without PCOS who had > or=1 live birth ( 262 live births ) . RESULTS There were 101 out of 126 ( 80 % ) term ( > or=37 gestational weeks ) PCOS births , which was not significantly different ( P = 0.7 ) from controls , 206 out of 252 ( 81.7 % ) . There were two ( 1.6 % ) birth defects . GD occurred in nine out of 119 PCOS pregnancies ( 7.6 % ) versus 40 out of 251 ( 15.9 % ) controls , P = 0.027 . The prevalence of pre-eclampsia did not differ in PCOS versus control pregnancies ( 4.1 versus 3.6 % , P = 0.8 ) . The birth length and weight of the 52 male neonates did not differ ( P > 0.05 ) from those of CDC males ; the 74 female neonates were shorter than CDC females ( 48.9 + /- 5.4 versus 50.6 + /- 2.7 cm , P = 0.006 ) and weighed less ( 3.09 + /- 0.85 versus 3.29 + /- 0.52 kg , P = 0.04 ) . There were no systematic differences in growth between PCOS and CDC infants over 18 months . At 3 , 6 , 9 , 12 and 18 months , of a potential 100 % motor-social development score , scores ( + /-SD ) were 95 + /- 13 , 98 + /- 8 % , 95 + /- 10 , 97 + /- 8 and 94 + /- 16 % ; no infants had motor-social developmental delays . CONCLUSIONS Metformin reduced development of GD , was not teratogenic and did not adversely affect birth length and weight , growth or motor-social development in the first 18 months of life The Metformin in Gestational Diabetes ( MiG ) trial is a prospect i ve r and omized multicenter trial in women with gestational diabetes mellitus ( GDM ) that is testing the hypothesis that metformin treatment , compared with insulin , is associated with similar perinatal outcomes , improved markers of insulin sensitivity in the mother and baby , and improved treatment acceptability . Women with GDM who are at 20–33 weeks ’ gestation in a singleton pregnancy and meet entry criteria are r and omized to insulin or metformin  treatment . The primary outcome is a composite of neonatal morbidity , with 750 recruits required . The trial finished recruiting in October 2006 . Interim data on 200 women ( and subsequently 550 women ) have been review ed by the data safety monitoring committee , which has reported that the trial should answer the hypotheses and no protocol changes are required . Data from 457 women show recruits are a mean age of 33.3 ± 5.3 years ; BMI of 32.1 ± 7.8 kg/m2 ; and ethnicity 47.2 % European/Caucasian , 25.7 % Polynesian , and 24.3 % Indian/Asian .  The mean fasting glucose at recruitment is 5.3 ± 1.1 mmol/l and A1C is 5.7 ± 0.8 % . Long-term follow-up of children started at age 2 years , with assessment s of body composition , neurodevelopment , diet , and activity levels . The MiG trial will address the efficacy and detailed safety of metformin compared with insulin in women with GDM . Long-term follow-up of offspring will examine whether treatment influences later health ( Australasian Clinical Trials Registry number 12605000311651 ) . GDM is diagnosed in over 4 % of pregnant women ( 1,2 ) . The prevalence is increasing as the pregnancy population becomes older and fatter . Women with GDM have increased rates of pregnancy complications and risks of later type 2 diabetes ( 1,2 ) . The offspring of women with GDM also have increased risks of perinatal complications and long-term risks of obesity and type 2 diabetes ( 1– OBJECTIVE To compare the efficacy of metformin with insulin in the management of  pregnancy with diabetes .  STUDY DESIGN R and omized clinical trial . PLACE AND DURATION OF STUDY Department of Obstetrics and Gynaecology , Maternal and Child Health Centre ( MCH ) , Pakistan Institute of Medical Sciences , Islamabad , from May 2010 to January 2011 . METHODOLOGY A total of 68 pregnant patients with diabetes were included in this study . Patients were r and omly divided in to two groups of each 34 patients based on table of r and om numbers . One was labelled as group-A and other was labelled as group-B. Group-A received insulin and group-B received metformin for the management of diabetes . RESULTS The mean age was 29.82 ± 4.58 and 29.35 ± 4.97 years in groups-A and B respectively . Fasting blood sugar level after 1 month was controlled in 22 ( 64.7 % ) patients in group-A and in 27 ( 79.4 % ) in group-B ( p > 0.05 ) . Fasting blood sugar level at term , remained controlled in 30 ( 88.2 % ) patients in group-A and 27 ( 79.4 % ) in group-B ( p > 0.05 ) . Comparison of r and om blood sugar levels within normal limits after 1 month in 25 ( 73.5 % ) in group-A and in 24 ( 70.6 % ) in group-B. At term , r and om blood sugar level was controlled in 28 ( 82.4 % ) and 27 ( 79.4 % ) patients in group-A and B , respectively . Comparison of post-treatment HBA1C level depicts that diabetes controlled in 27 ( 79.4 % ) patients in group-A while in 28 ( 82.3 % ) patients of group-B. The efficacy of metformin and insulin in controlling diabetes was equal in two groups . CONCLUSION There was no marked difference in efficacy of metformin and insulin in controlling diabetes in pregnant patients in two groups OBJECTIVE To determine the degree of placental transfer of rosiglitazone in early human pregnancy . DESIGN Prospect i ve observational study . SETTING University teaching hospital . PATIENT(S ) Thirty-one women undergoing surgical termination of pregnancy between 8 and 12 weeks ' gestation . INTERVENTION(S ) Each woman was given two doses of rosiglitazone ( 4 mg ) before the procedure . MAIN OUTCOME MEASURE(S )  Rosiglitazone concentration in fetal tissue and coelomic and amniotic fluids . RESULT ( S ) The mean maternal serum rosiglitazone concentration was 110.3 + /- 47.9 ng/mL. Rosiglitazone was detectable in 19 fetal sample s ( 61.3 % ) . The mean fetal tissue concentration was 52.7 + /- 26.3 ng/g . Rosiglitazone was more likely to be detected in fetal tissue if the gestation at termination was 10 weeks or more compared with earlier gestation . Coelomic fluid was obtained in 22 cases , and rosiglitazone was detected in 13 sample s ( 59.1 % ) . The mean concentration was 22.8 + /- 7.0 ng/mL. Rosiglitazone was detectable in only two of the 31 amniotic fluid sample s , with concentrations of 10.3 and 12.6 ng/mL. CONCLUSION ( S ) The risk of placental transfer of rosiglitazone is much higher at or after 10 weeks of gestation . Absence of detectable rosiglitazone in amniotic fluid despite its presence in fetal tissue suggests that fetuses may have the ability to metabolize rosiglitazone , and little parent drug was excreted unchanged in urine Purpose The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus . Methods The current non-inferiority r and omized controlled trial was conducted at Ain Shams University Maternity Hospital . The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks , who showed insulin resistance ( defined as poor glycemic control at a daily dose of ≥1.12 units/kg ) . Recruited women were r and omized into one of two groups : group I , including women who received oral metformin without increasing the insulin dose ; and group II , including women who had their insulin dose increased . The primary outcome was maternal glycemic control . Secondary outcomes included maternal bouts of hypoglycemia , need for another hospital admission for uncontrolled diabetes during pregnancy , gestational age at delivery , mode of delivery , birth weight , birth trauma , congenital anomalies , 1- and 5-min Apgar score , neonatal hypoglycemia , need for neonatal intensive care unit ( NICU ) admission and adverse neonatal outcomes . Results A total number of 154 women with diabetes mellitus with pregnancy were approached ; of them 90 women were eligible and were r and omly allocated and included in the final analysis . The recruited 90 women were r and omized into one of two groups : group I ( metformin group ) ( n = 46 ) , including women who received oral metformin in addition to the same initial insulin dose ; and group II ( control group ) ( n = 44 ) , including women who had their insulin dose increased according to the st and ard protocol . The mean age of included women was 29.84 ± 5.37 years ( range 20–42 years ) . The mean gestational age at recruitment was 28.7 ± 3.71 weeks ( range 21–34 weeks ) . Among the 46 women of group I , 17 ( 36.9 % ) women reached proper glycemic control at a daily metformin dose of 1,500 mg , 18 ( 39.2 % ) at a daily dose of 2,000 mg , while 11 ( 23.9 % ) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose . Conclusion Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women , along with benefits of reduced hospital stay , reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia , NICU admission and neonatal respiratory distress syndrome Two oral hypoglycaemic agents , metformin and glibenclamide , have been compared with insulin in separate large r and omised controlled trials and have been found to be as effective as insulin in gestational diabetes .  However , very few trials have compared metformin with glibenclamide Background Gestational diabetes mellitus ( GDM ) is an increasingly prevalent risk factor for type 2 diabetes . We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year . Methods and Findings In this study , 573 women were r and omised to either the intervention ( n = 284 ) or usual care ( n = 289 ) . At baseline , 10 % had impaired glucose tolerance and 2 % impaired fasting glucose . The diabetes prevention intervention comprised one individual session , five group sessions , and two telephone sessions . Primary outcomes were changes in diabetes risk factors ( weight , waist circumference , and fasting blood glucose ) , and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors . The mean changes ( intention-to-treat [ ITT ] analysis ) over 12 mo were as follows : −0.23 kg body weight in intervention group ( 95 % CI −0.89 , 0.43 ) compared with + 0.72 kg in usual care group ( 95 % CI 0.09 , 1.35 ) ( change difference −0.95 kg , 95 % CI −1.87 , −0.04 ; group by treatment interaction p = 0.04 ) ; −2.24 cm waist measurement in intervention group ( 95 % CI −3.01 , −1.42 ) compared with −1.74 cm in usual care group ( 95 % CI −2.52 , −0.96 ) ( change difference −0.50 cm , 95 % CI −1.63 , 0.63 ; group by treatment interaction p = 0.389 ) ; and + 0.18 mmol/l fasting blood glucose in intervention group ( 95 % CI 0.11 , 0.24 ) compared with + 0.22 mmol/l in usual care group ( 95 % CI 0.16 , 0.29 ) ( change difference −0.05 mmol/l , 95 % CI −0.14 , 0.05 ; group by treatment interaction p = 0.331 ) . Only 10 % of women attended all sessions , 53 % attended one individual and at least one group session , and 34 % attended no sessions . Loss to follow-up was 27 % and 21 % for the intervention and control groups , respectively , primarily due to subsequent pregnancies . Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline . Conclusions Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk , the level of engagement during the first postnatal year was low . Further research is needed to improve engagement , including participant involvement in study design ; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention . Trial Registration Australian New Zeal and Clinical Trials Registry AIMS To evaluate the effect of metformin and insulin in glycemic control and compare pregnancy outcome in women with gestational diabetes mellitus ( GDM ) . METHODS This r and omized controlled trial was conducted in GDM women with singleton pregnancy and gestational age between 20 and 34 weeks who did not achieve glycemic control on diet were assigned r and omly to receive either metformin ( n=80 ) or insulin ( n=80 ) . The primary outcomes were maternal glycemic control and birth weight . The secondary outcomes were neonatal and obstetric complications . RESULTS Two groups were comparable regarding the maternal characteristics . Two groups were similar in mean FBS ( P=0.68 ) and postpr and ial measurements ( P=0.87 ) throughout GDM treatment . The neonates of metformin group had less rate of birth weight centile > 90 than insulin group ( RR : 0.5 , 95 % CI : 0.3 - 0.9 , P=0.012 ) . Maternal weight gain was reduced in the metformin group ( P<0.001 ) . Two groups were comparable according to neonatal and obstetric complications ( P>0.05 ) . In metformin group 14 % of women needed to supplemental insulin to achieve euglycemia . CONCLUSION Metformin is an effective and safe alternative treatment to insulin for women with GDM . This study does not show significant risk of maternal or neonatal adverse outcome with the use of metformin OBJECTIVES To study a possible effect of metformin on the uteroplacental circulation . METHODS Forty pregnant women with polycystic ovary syndrome ( PCOS ) were enrolled in a r and omized , double-blind , placebo-controlled trial of metformin ( 1700 mg/day ) during pregnancy . Doppler ultrasound examinations of the uterine arteries were performed at 12 , 19 , 24 , 32 and 36 gestational weeks and of the umbilical artery at 19 , 24 , 32 and 36 gestational weeks . RESULTS There was a greater mean bilateral uterine artery pulsatility index ( PI ) at 12 weeks ( 1.95 vs. 1.58 , P = 0.02 ) , and a greater reduction in mean PI from 12 to 19 weeks ( P = 0.03 ) in metformin-treated women . There were no differences in mean PI values between groups at 19 , 24 , 32 or 36 gestational weeks . Pregnancy complications , such as preterm delivery before 32 weeks , severe pre-eclampsia or serious postpartum events , occurred only in the placebo group ( 7 of 22 vs. 0 of 18 , P = 0.01 ) . There were no associations between uterine artery Doppler measurements and pregnancy complications . We found no differences between groups in mean umbilical artery PI at 19 , 24 , 32 or 36 gestational weeks . CONCLUSIONS In this small r and omized trial , metformin treatment in pregnancy reduced uterine artery impedance between 12 and 19 weeks of gestation , and this was associated with reduced complication rate . Published by John Wiley & Sons , OBJECTIVE Gestational diabetes affects up to 5 % of women .  Oral hypoglycemics have been avoided because of the assumption that their placental transfer may cause fetal-neonatal hypoglycemia . A recent r and omized trial could not show measurable glyburide levels in umbilical blood despite maternal treatment with regular doses of glyburide . The mechanism underlying this phenomenon is not known . The objective of our study was to document , using a human placenta perfusion model , whether glyburide is actively effluxed from the fetal to the maternal circulation . STUDY DESIGN In vitro perfusion studies of human cotyledon were performed to quantify placental transfer of glyburide . Using close circle experiments and introducing glyburide to both maternal and fetal circulations at 200 ng/mL , we looked for evidence of transport against concentration gradient from the fetus to the mother . In parallel experiments , the P-glycoprotein inhibitor verapamil was used in an attempt to inhibit transplacental glyburide movement . RESULTS There was highly significant transfer of glyburide against concentration gradient from the fetal to the maternal circulation . Fetal-to-maternal concentration ratio was 0.92 + /- 0.23 at the start of the experimental period and 0.31 + /- 0.47 3 hours later ( P = .01 ) ( n = 5 ) . Verapamil did not modify glyburide transport . CONCLUSION This is the first direct evidence of active glyburide transport from the fetus to the mother and , in general , of any medicinal drug used during pregnancy . These experiments suggest that glyburide is actively efflux by a transporter other than P-glycoprotein . Alternatively , it is possible that a minority of glyburide is carried by P-glycoprotein , but most of the fetal load is pumped to the mother by a yet-unidentified placental transport system OBJECTIVE : To evaluate whether the addition of glyburide to diet therapy modifies pregnancy outcomes in women with mild gestational diabetes . METHODS : Women with at least two abnormal values on a 3-hour , 100-g oral glucose tolerance test according to National Diabetes Data Group criteria and fasting values less than 105 mg/dL between 24 and 30 weeks of gestation were r and omized to blinded glyburide or placebo study drug . All women were placed on a 35-kcal/kg diet and recorded four times daily capillary glucose measurements . The study drug was titrated based on weekly maternal capillary glucose values with targets of less than 95 mg/dL ( 5.3 mmol/L ) and 120 mg/dL ( 6.7 mmol/L ) for fasting and 2-hour postpr and ial glucose measurements , respectively . The primary study outcome was a 200-g birth weight decrement in neonates of women treated with glyburide . The sample size estimate for this outcome was 334 total r and omized women with a one-to-one allocation . RESULTS : A total of 395 women were enrolled at a single center between September 2008 and October 2012 . Women treated with glyburide had a significantly greater decline in fasting glucose values over the course of therapy . However , there was no difference in the primary study outcome . Specifically , the mean birth weight was 33 g lower in the group treated with glyburide ( P=.52 ) . Although not powered to examine all outcomes associated with gestational diabetes , treatment with glyburide did not affect need for operative delivery , shoulder dystocia , clavicular fracture , Erb 's palsy , or neonatal hypoglycemia . Four women in each group required insulin . CONCLUSION : The addition of glyburide to diet therapy significantly improved maternal glycemic control over time when compared with placebo . However , adding glyburide to diet did not decrease birth weight or improve maternal or neonatal outcomes in women with mild gestational diabetes . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00744965 . LEVEL OF EVIDENCE : OBJECTIVE To compare the safety and tolerability of metformin to insulin for glycemic control among women with preexisting type 2 and early A2 gestational diabetes . STUDY DESIGN Women with preexisting type 2 diabetes and those diagnosed with gestational diabetes who required medical management prior to 20 weeks were r and omly assigned to metformin or insulin . Glycemic control , defined as > 50 % capillary blood glucose within target range , was compared between groups . Other outcomes included patient tolerance , neonatal and obstetric complications , maternal weight gain , neonatal cord blood C-peptide , and patient satisfaction with therapy . RESULTS Twenty-eight women completed the study , with 14 in each group . Of the 15 women assigned to metformin , 100 % continued to receive metformin until delivery , although 43 % required supplemental insulin to achieve glycemic control . Glucose measures did not differ between the groups , and the proportion who met fasting and postpr and ial glycemic target values did not differ between the groups . Women treated with metformin had significantly fewer subjective episodes of hypoglycemia compared with those using insulin ( 0 % versus 36 % ; p = 0.04 ) as well as reported glucose values < 60 mg/dL ( 7.1 % versus 50 % ; p = 0.03 ) . CONCLUSION Metformin should be considered for treatment of overt diabetes and early A2 gestational diabetes in pregnancy BACKGROUND Women with gestational diabetes mellitus are rarely treated with a sulfonylurea drug , because of concern about teratogenicity and neonatal hypoglycemia . There is little information about the efficacy of these drugs in this group of women . METHODS We studied 404 women with singleton pregnancies and gestational diabetes that required treatment . The women were r and omly assigned between 11 and 33 weeks of gestation to receive glyburide or insulin according to an intensified treatment protocol . The primary end point was achievement of the desired level of glycemic control . Secondary end points included maternal and neonatal complications . RESULTS The mean ( + /-SD ) pretreatment blood glucose concentration as measured at home for one week was 114+/-19 mg per deciliter ( 6.4+/-1.1 mmol per liter ) in the glyburide group and 116+/-22 mg per deciliter ( 6.5+/-1.2 mmol per liter ) in the insulin group ( P=0.33 ) . The mean concentrations during treatment were 105+/-16 mg per deciliter ( 5.9+/-0.9 mmol per liter ) in the glyburide group and 105+/-18 mg per deciliter ( 5.9+/-1.0 mmol per liter ) in the insulin group ( P=0.99 ) . Eight women in the glyburide group ( 4 percent ) required insulin therapy . There were no significant differences between the glyburide and insulin groups in the percentage of infants who were large for gestational age ( 12 percent and 13 percent , respectively ) ; who had macrosomia , defined as a birth weight of 4000 g or more ( 7 percent and 4 percent ) ; who had lung complications ( 8 percent and 6 percent ) ; who had hypoglycemia ( 9 percent and 6 percent ) ; who were admitted to a neonatal intensive care unit ( 6 percent and 7 percent ) ; or who had fetal anomalies ( 2 percent and 2 percent ) . The cord-serum insulin concentrations were similar in the two groups , and glyburide was not detected in the cord serum of any infant in the glyburide group . CONCLUSIONS In women with gestational diabetes , glyburide is a clinical ly effective alternative to insulin therapy BACKGROUND It is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes . METHODS Women who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus ( i.e. , an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [ 5.3 mmol per liter ] ) were r and omly assigned to usual prenatal care ( control group ) or dietary intervention , self-monitoring of blood glucose , and insulin therapy , if necessary ( treatment group ) . The primary outcome was a composite of stillbirth or perinatal death and neonatal complications , including hyperbilirubinemia , hypoglycemia , hyperinsulinemia , and birth trauma . RESULTS A total of 958 women were r and omly assigned to a study group--485 to the treatment group and 473 to the control group . We observed no significant difference between groups in the frequency of the composite outcome ( 32.4 % and 37.0 % in the treatment and control groups , respectively ; P=0.14 ) . There were no perinatal deaths . However , there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes , including mean birth weight ( 3302 vs. 3408 g ) , neonatal fat mass ( 427 vs. 464 g ) , the frequency of large-for-gestational-age infants ( 7.1 % vs. 14.5 % ) , birth weight greater than 4000 g ( 5.9 % vs. 14.3 % ) , shoulder dystocia ( 1.5 % vs. 4.0 % ) , and cesarean delivery ( 26.9 % vs. 33.8 % ) . Treatment of gestational diabetes mellitus , as compared with usual care , was also associated with reduced rates of preeclampsia and gestational hypertension ( combined rates for the two conditions , 8.6 % vs. 13.6 % ; P=0.01 ) . CONCLUSIONS Although treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications , it did reduce the risks of fetal overgrowth , shoulder dystocia , cesarean delivery , and hypertensive disorders . ( Clinical Trials.gov number , NCT00069576 . AIM To test the hypothesis that myoinositol supplementation will improve insulin sensitivity as measured by markers of insulin resistance such as homeostasis model assessment of insulin resistance and adiponectin in women with gestational diabetes . METHODS The trial was carried out in diet-treated patients with gestational diabetes diagnosed in our department between April 2008 and September 2009 . Subjects were r and omly assigned to receive either myoinositol supplementation ( 4 g daily ) plus folic acid ( 400 μg daily)-the study group-or folic acid only ( 400 μg daily)-the control group . Both groups received the same diet prescription . Homeostasis model assessment of insulin resistance and adiponectin were assayed while fasting at the time of the diagnostic oral glucose tolerance test and after 8 weeks of treatment . RESULTS There were 69 evaluable patients , 24 in the study group and 45 in the control group . Fasting glucose and insulin , and consequently homeostasis model assessment of insulin resistance , decreased in both groups ( 50 % in the study group vs. 29 % in the control group ) , but the decline in the study group was significantly greater than that in the control group ( P = 0.0001 ) . Adiponectin increased in the myoinositol group while it decreased in the control group ( P = 0.009 ) . CONCLUSION Myoinositol improves insulin resistance in patients with gestational diabetes BACKGROUND This study assessed the views of the women who participated in the DIAMIND r and omised trial of postpartum SMS reminders to test for type 2 diabetes after gestational diabetes ( GDM ) on their preferred type of postpartum reminder system and barriers and facilitators to completion of postpartum diabetes testing . METHOD A written question naire was sent to women with recent GDM who participated in the DIAMIND trial ( n=276 ) via post or email at six months after the birth of their baby . RESULTS 208 women ( 75 % ) returned the study question naires . Preferred postpartum reminder types were : SMS ( 67 % ) , email ( 17 % ) , postal ( 12 % ) and voice call ( 1 % ) . Women who had not yet completed an OGTT indicated that they planned to undertake one in the future ( 61 % ) . Common barriers to postpartum OGTT completion included : not having enough time ( 73 % ) , inadequate childcare ( 30 % ) , and a need to focus on the health of the baby ( 30 % ) . The most common facilitator was having a shorter test ( 33 % ) . CONCLUSIONS Improved childcare quality and access as well as more research into a shorter , more convenient test procedure for type 2 diabetes screening are needed . Reminder systems for postpartum diabetes screening should be electronic where possible
BACKGROUND While most guidance recommends the use of insulin in women whose pregnancies are affected by pre-existing diabetes , oral anti-diabetic agents may be more acceptable to women .
The effects of these oral anti-diabetic agents on maternal and infant health outcomes need to be established in pregnant women with pre-existing diabetes or impaired glucose tolerance , as well as in women with previous gestational diabetes mellitus preconceptionally or during a subsequent pregnancy .
This review is an up date of a review that was first published in 2010 .
OBJECTIVES To investigate the effects of oral anti-diabetic agents in women with established diabetes , impaired glucose tolerance or previous gestational diabetes who are planning a pregnancy , or pregnant women with pre-existing diabetes , on maternal and infant health .
The use of oral anti-diabetic agents for the management of gestational diabetes in a current pregnancy is evaluated in a separate Cochrane Review .