***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE To compare the degree of insulin resistance in women with gestational diabetes mellitus ( GDM ) who do and do not develop preeclampsia . RESEARCH DESIGN AND METHODS We conducted a prospect i ve cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests ( OGTTs ) , intravenous glucose tolerance tests ( IVGTTs ) , and glucose clamp studies in the early third trimester ( n = 150 ) and 15 months postpartum ( n = 89 ) . After delivery , the women were categorized as nonpreeclamptic or preeclamptic ( systolic blood pressure [ SBP ] > or = 140 mmHg , diastolic blood pressure [ DBP ] > or = 90 mmHg , and at least > 1 + proteinuria or > 300 mg/24 h ) . Metabolic parameters between the groups were compared by chi2 or Fisher 's exact tests and ANOVA with P < 0.05 as significant . RESULTS A total of 29 women ( 19 % ) developed preeclampsia , which was mild in 21 and severe in 8 women . At entry , there were no differences in age , weight indexes , and glycemic measures between the nonpreeclamptic and preeclamptic groups . Those with preeclampsia were significantly taller ( 61.5 + /- 2.4 vs. 60.1 + /- 2.3 in , P = 0.003 ) , were more often nulliparous ( 38 vs. 16 % , P = 0.01 ) , and had higher entry SBP ( 112 + /- 10 vs. 103 + /- 6.9 mmHg , P < 0.0001 ) and DBP ( 64 + /- 9 vs. 59 + /- 5 mmHg , P = 0.002 ) . No significant differences between the groups were found in any measures of the OGTT glucose levels , insulin sensitivity index , glucose effectiveness , acute response to glucose , or disposition index , nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose , insulin , free fatty acid , hepatic glucose output , peripheral glucose clearance , C-peptide , or glucagon . At 15 months postpartum , blood pressure levels remained significantly higher in the preeclamptic group ( n = 19 ) compared with the nonpreeclamptic group ( n = 70 ) . No differences in any glycemic or insulin resistance measures were found . CONCLUSIONS Women with GDM were uniformly insulin resistant . Those who developed preeclampsia , when compared with those who remained nonpreeclamptic , were not more insulin resistant in either the third trimester or 15 months postpartum . However , women who developed preeclampsia had blood pressure levels that were significantly higher , although still in the normal range , than those of women who remained nonpreeclamptic 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 Please cite this paper as : Ijäs H , Vääräsmäki M , Morin‐Papunen L , Keravuo R , Ebeling T , Saarela T , Raudaskoski T. Metformin should be considered in the treatment of gestational diabetes : a prospect i ve r and omised study . BJOG 2011;118:880–885 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 ) AIM To compare treatment with metformin alone , metformin plus insulin and insulin alone in women with gestational diabetes ( GDM ) . METHOD A total of 150 gestational diabetic patients who fulfilled the eligibility criteria were included in this prospect i ve r and omized control open labeled study . A risk factor based screening was done followed by a GCT and then local GTT criteria from antenatal clinics . They were initially divided into two groups with odd numbers assigned to metformin treatment and even numbers to insulin treatment . Metformin and /or insulin treatment was given and target blood sugar levels aim ed at FBS ≤ 100 mg/dl and postpr and ial levels ≤ 126 mg/dl . Supplemental insulin was added to metformin treatment group to maintain the glycemic targets if required . Patients were followed until delivery and maternal fetal outcomes and pharmacotherapeutic characteristics were recorded on a performa . RESULTS Less maternal weight gain was found in the metformin treated groups ( 9.8 ± 1.5 kg [ metformin alone ] vs. 9.8 ± 1.4 kg [ metformin plus insulin ] vs. 12.5 ± 1.1 kg [ insulin alone ] P < 0.000 ) . Preeclampsia was significantly less in metformin treated groups . There were no perinatal deaths in the study . Mean birth weight was significantly less in metformin treated groups ( 3.4 ± 0.4 kg vs. 3.3 ± 0.5 kg vs. 3.7 ± 0.5 kg P < 0.01 ) . Less neonatal morbidity was observed in metformin groups . 42.7 % of patients required supplemental insulin ( mean dose of 13.6 ± 2 units ) in the  metformin group . Mean gestational age at which insulin was added was 31.8 ± 5.9 weeks . CONCLUSION Metformin is an effective and cheap treatment option for women with gestational diabetes with or without supplemental insulin Summary Background Results of several trials of antioxidant use during pregnancy have not shown a reduction in pre-eclampsia , but the effect in women with diabetes is unknown . We aim ed to assess whether supplementation with vitamins C and E reduced incidence of pre-eclampsia in women with type 1 diabetes . Methods We enrolled women from 25 UK antenatal metabolic clinics in a multicentre r and omised placebo-controlled trial . Eligibility criteria were type 1 diabetes preceding pregnancy , presentation between 8 weeks ' and 22 weeks ' gestation , singleton pregnancy , and age 16 years or older . Women were r and omly allocated in a 1:1 ratio to receive 1000 mg vitamin C and 400 IU vitamin E ( α-tocopherol ) or matched placebo daily until delivery . The r and omisation sequence was stratified by centre with balanced blocks of eight patients . All trial personnel and participants were masked to treatment allocation . The primary endpoint was pre-eclampsia , which we defined as gestational hypertension with proteinuria . Analysis was by modified intention to treat . This study is registered , IS RCT N27214045 . Findings Between April , 2003 , and June , 2008 , 762 women were r and omly allocated to treatment groups ( 379 vitamin supplementation , 383 placebo ) . The primary endpoint was assessed for 375 women allocated to receive vitamins , and 374 allocated to placebo . Rates of pre-eclampsia did not differ between vitamin ( 15 % , n=57 ) and placebo ( 19 % , 70 ) groups ( risk ratio 0·81 , 95 % CI 0·59–1·12 ) . No adverse maternal or neonatal outcomes were reported . Interpretation Supplementation with vitamins C and E did not reduce risk of pre-eclampsia in women with type 1 diabetes . However , the possibility that vitamin supplementation might be beneficial in women with a low antioxidant status at baseline needs further testing . Funding The Wellcome Trust BACKGROUND Obesity is associated with an increased risk of adverse pregnancy outcomes . Lifestyle-intervention studies have not shown improved outcomes . Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned pregnant women without diabetes who had a body-mass index ( BMI ; the weight in kilograms divided by the square of the height in meters ) of more than 35 to receive metformin , at a dose of 3.0 g per day , or placebo ( 225 women in each group ) from 12 to 18 weeks of gestation until delivery . The BMI was calculated at the time of study entry ( 12 to 18 weeks of gestation ) . The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD ( equivalent to a 50 % reduction , from 20 % to 10 % , in the incidence of large-for-gestational-age neonates ) . Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia , as well as the incidence of adverse neonatal outcomes . R and omization was performed with the use of computer-generated r and om numbers . The analysis was performed according to the intention-to-treat principle . RESULTS A total of 50 women withdrew consent during the trial , which left 202 women in the metformin group and 198 in the placebo group . There was no significant between-group difference in the median neonatal birth-weight z score ( 0.05 in the metformin group [ interquartile range , -0.71 to 0.92 ] and 0.17 in the placebo group [ interquartile range , 
    Output:
    
No heterogeneity was present in the metformin vs. insulin analysis of r and omized controlled trials , whereas high levels of heterogeneity were present in studies comparing metformin with placebo/control .
Pre-eclampsia was a secondary outcome in most of the studies .
In studies r and omizing pregnant women to glucose-lowering therapy , metformin was associated with lower gestational weight gain and a lower risk of pre-eclampsia compared with insulin