***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: Objectives . The prevalence of type 2 diabetes in American adolescents has increased markedly during the past generation . Although the factors that contribute to the development of type 2 diabetes are complex and not wholly eluci date d , the triad of severe obesity , hyperinsulinemia , and a family history of type 2 diabetes places a child at an increased risk for development of the disease . Current approaches to the prevention of type 2 diabetes , including dietary counseling and exercise , have had limited success . We reasoned that drugs that increase glucose tolerance in diabetic patients might prove useful in preventing the progression to glucose intolerance in high-risk patients . To that end , we conducted a double-blind , placebo-controlled study of the effects of metformin  on body mass index ( BMI ) , serum leptin , glucose tolerance , and serum lipids in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes . Methods . The study population consisted of 29 white and black adolescents aged 12 to 19 years . All had BMI s exceeding 30 kg/m2 . Criteria for enrollment included : 1 ) a fasting insulin concentration exceeding 15 μU/mL ; and 2 ) at least 1 first- or second-degree relative with type 2 diabetes . All patients had fasting plasma glucose concentrations < 110 mg% and hemoglobin A1c concentrations ≤6.0 % . All had normal linear growth and sexual development for age , with no marked hirsutism , severe acne , or menstrual irregularities characteristic of polycystic ovary syndrome . Eight participants had acanthosis nigricans . After baseline laboratory studies including a rapidly sample d intravenous glucose tolerance test , patients were r and omized to receive metformin ( 500 mg twice daily ) or a placebo for a total of 6 months . The effects of metformin  on BMI st and ard deviation score , serum leptin , glucose tolerance , and serum lipids were analyzed . The study was double-blinded and included no specific dietary restrictions . Results . Metformin caused a decline of 0.12 st and ard deviation in BMI in study participants ( −1.3 % from baseline ) , and a 5.5 % reduction in serum leptin in girls . In contrast , BMI and serum leptin rose 0.23 st and ard deviation ( 2.3 % ) and 16.2 % , respectively , in the placebo group during the treatment period . Metformin caused a progressive decline in fasting blood glucose ( from a mean of 84.9 to 75.1 mg% ) and a reduction in fasting insulin levels ( from 31.3 to 19.3 μU/mL ) . In contrast , fasting glucose levels in the placebo group rose slightly from 77.2 to 82.3 mg% , and fasting insulin levels did not change . Insulin sensitivity , as assessed by the ratio of fasting insulin to glucose concentrations and the quantitative insulin sensitivity check index ( 1/[log fasting insulin + log fasting glucose ] ) and homeostasis model assessment insulin resistance index ( fasting insulin × fasting glucose/22.5 ) indices , increased slightly in the metformin-treated participants . However , the insulin sensitivity measured using Bergman 's minimal model did not change . There were also no significant changes in glucose effectiveness , hemoglobin A1c , serum lipids , or serum lactate in the metformin or placebo groups . Metformin was tolerated well by the majority of patients . Transient abdominal discomfort or diarrhea occurred in 40 % of treated participants ; there were no episodes of vomiting or lactic acidosis . Conclusions . The treatment of obesity and insulin resistance in adults often proves ineffective because the vicious cycle leading to type 2 diabetes may have become entrenched and , to some extent , may be irreversible . Early detection and therapy of the obese adolescent with a family history of type 2 diabetes may interrupt the cycle of weight gain and insulin resistance that leads to glucose intolerance in adulthood . Through its ability to reduce fasting blood glucose and insulin concentrations and to moderate weight gain , metformin might complement the effects of dietary and exercise counseling and reduce the risk of type 2 diabetes in selected patients The present study is an evaluation of metformin ’s effect on BMI z score , insulin sensitivity , and inflammation and cardiovascular risk factors in prepubertal and pubertal children who are obese . OBJECTIVES : Metformin has shown its effectiveness in treating obesity in adults . However , little research has been conducted in children , with a lack of attention on pubertal status . The objectives were to determine whether oral metformin treatment reduces BMI z score , cardiovascular risk , and inflammation biomarkers in children who are obese depending on pubertal stage and sex . METHODS : This was a r and omized , prospect i ve , double-blind , placebo-controlled , multicenter trial , stratified according to pubertal stage and sex , conducted at 4 Spanish clinical hospitals . Eighty prepubertal and 80 pubertal nondiabetic children who were obese aged 7 to 14 years with a BMI > 95th percentiles were recruited . The intervention included 1 g/d of metformin versus placebo for 6 months . The primary outcome was a reduction in BMI z score . Secondary outcomes comprised insulin resistance , cardiovascular risk , and inflammation biomarkers . RESULTS : A total of 140 children completed the study ( 72 boys ) . Metformin  decreased the BMI z score  versus placebo in the prepubertal group ( −0.8 and −0.6 , respectively ; difference , 0.2 ; P = .04 ) . Significant increments were observed in prepubertal children treated with metformin versus placebo recipients in the quantitative insulin sensitivity check index ( 0.010 and −0.007 ; difference , 0.017 ; P = .01 ) and the adiponectin – leptin ratio ( 0.96 and 0.15 ; difference , 0.81 ; P = .01 ) and declines in interferon-γ ( −5.6 and 0 ; difference , 5.6 ; P = .02 ) and total plasminogen activator inhibitor-1 ( −1.7 and 2.4 ; difference , 4.1 ; P = .04 ) . No serious adverse effects were reported . CONCLUSIONS : Metformin  decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters in prepubertal children but not in pubertal children . Hence , the differential response according to puberty might be related to the dose of metformin per kilogram of weight . Further investigations are necessary INTRODUCTION Although the Diabetes Prevention Program and other clinical trials demonstrated the efficacy of intensive lifestyle interventions ( ILI ) and metformin to prevent type 2 diabetes , no studies have tested their comparative effects in pragmatic setting s. This study was design ed to compare the real-world effectiveness of ILI , metformin , and st and ard care among Hispanic women ( Latinas ) with prediabetes . STUDY DESIGN RCT . SETTING / PARTICIPANTS Ninety-two Latinas , who had a mean hemoglobin A1c of 5.9 % , BMI of 33.3 kg/m2 , and waist circumference of 97.4 cm ( 38.3 inches ) , were recruited from an urban community and r and omly assigned to ILI , metformin , or st and ard care using 1:1:1 allocation . Data were collected from 2013 - 2015 and analyzed in 2016 . INTERVENTION The 12-month ILI was adapted from the Diabetes Prevention Program 's ILI and delivered by community health workers ( promotoras ) over 24 sessions . Metformin participants received 850 mg twice daily . Those r and omized to st and ard care continued their regular medical care . MAIN OUTCOME MEASURES Weight and secondary outcomes ( waist circumference , blood pressure , hemoglobin A1c , fasting plasma glucose , insulin , and lipids ) were assessed at baseline and 12 months . RESULTS ILI participants demonstrated significantly greater mean weight loss ( -4.0 kg , 5.0 % ) than metformin ( -0.9 kg , 1.1 % ) and st and ard care participants ( + 0.8 kg , 0.9 % ) ( p<0.001 ) . The difference in weight loss between metformin and st and ard care was not significant . The ILI group experienced a greater reduction in waist circumference than st and ard care ( p=0.001 ) , and a marginal improvement in hemoglobin A1c compared with metformin and st and ard care ( p=0.063 ) . CONCLUSIONS In the first comparative effectiveness trial of diabetes prevention treatments , a 12-month ILI produced significantly greater weight loss than metformin and st and ard care among Latinas with prediabetes . These data suggest that ILI delivered by promotoras is an effective strategy for preventing diabetes in this high-risk group , which may be superior to metformin . Future pragmatic trials involving larger sample s should examine differences in diabetes incidence associated with these treatments This study assessed the efficacy of adding metformin to a structured lifestyle intervention in reducing BMI in obese adolescents with insulin resistance . Obese adolescents ( 25 ) aged 10–16 years with a body mass index ( BMI ) > 95th percentile and insulin resistance ( Homeostasis Model Assessment —HOMA ) > 3.0 were assessed in a community clinic . A structured lifestyle intervention comprising nutritional and exercise education and motivational support in both individual and group sessions was delivered over 6 months . Subjects were r and omized to lifestyle intervention alone or with metformin ( 1500 g daily ) . The primary outcome measures were a change in BMI and modification of metabolic risk factors , including insulin resistance , plasma lipids and adipocytokines .  Eleven adolescents receiving lifestyle and metformin intervention and 14 receiving lifestyle alone completed the study .  BMI decreased by 1.8 kg/m2 with lifestyle and metformin but did not change with lifestyle alone . HOMA was significantly decreased in the lifestyle intervention group , but not following metformin , while the adiponectin/leptin ratio improved significantly in both groups . Dyslipidemic profiles improved most significantly with metformin . We conclude that metformin in combination with a 6-month structured lifestyle intervention is effective in reducing BMI in obese adolescents but did not improve insulin resistance . Lifestyle intervention , with or without metformin , improved metabolic risk factors such as plasma lipids and adipocytokines OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions , including abnormalities in glucose homeostasis in adolescents , but there are few data evaluating the efficacy of metformin  among younger children . Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children , who are insulin-resistant . RESEARCH DESIGN AND METHODS This study was a r and omized double-blind placebo-controlled trial consisting of 100 severely obese ( mean BMI 34.6 ± 6.6 kg/m2 ) insulin-resistant children aged 6–12 years , r and omized to 1,000 mg metformin  ( n = 53 )  or placebo  ( n = 47 ) twice daily for 6 months , followed by open-label metformin treatment  for 6 months . All children and their parents participated in a monthly dietitian-administered weight-reduction program . RESULTS Eighty-five percent completed the 6-month r and omized phase . Children prescribed metformin had significantly greater decreases in BMI ( difference −1.09 kg/m2 , CI −1.87 to −0.31 , P = 0.006 ) , body weight ( difference −3.38 kg , CI −5.2 to −1.57 , P < 0.001 ) , BMI Z score ( difference between metformin and placebo groups −0.07 , CI −0.12 to −0.01 , P = 0.02 ) , and fat mass ( difference −1.40 kg , CI −2.74 to −0.06 , P = 0.04 ) . Fasting plasma glucose ( P = 0.007 ) and homeostasis model assessment ( HOMA ) insulin resistance index ( P = 0.006 ) also improved more in metformin-treated children than in placebo-treated children . Gastrointestinal symptoms were significantly more prevalent in metformin-treated children , which limited maximal tolerated dosage in 17 % . During the 6-month open-label phase , children treated previously with placebo  decreased their BMI Z score ; those treated continuously with metformin did not significantly change BMI Z score further . CONCLUSIONS Metformin had modest but favorable effects on body weight , body composition , and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program Aims . To observe the rate of conversion from impaired glucose tolerance ( IGT ) to diabetes following lifestyle modification ( LSM ) or a combination of lifestyle and metformin compared to a control population with 1 
    Output:
    
Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention .
Conclusions The effects of metformin  on weight/ BMI vary , with smaller reductions in children than in adults .
This could be because of differences in adherence , daily dosage , and insulin status .
Metformin significantly reduced the progression toward T2DM in adults .