Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. Metformin in obese children and adolescents: the MOCA trial. A randomized, double-blind, placebo-controlled trial of metformin treatment for weight gain associated with initiation of risperidone in children and adolescents. The effect of comprehensive lifestyle intervention or metformin on obesity in young women. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Long-term metformin treatment in adolescents with obesity and insulin resistance, results of an open label extension study Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. Metformin for overweight women at midlife: a double-blind, randomized, controlled trial Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study Metformin in combination with structured lifestyle intervention improved body mass index in obese adolescents, but did not improve insulin resistance Metformin intervention in obese non-diabetic patients with breast cancer: phase II randomized, double-blind, placebo-controlled trial A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children Long-term treatment with metformin in obese, insulin-resistant adolescents: results of a randomized double-blinded placebo-controlled trial
Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus ( NIDDM ) . The mechanism may be attributed to decreased food intake . This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss .  Twelve diet-treated NIDDM women with obesity were r and omly given two dose levels ( 850 mg or 1700 mg ) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3x3 Latin square design . The number of s and wich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake , and the level of subjective hunger was rated just before the s and wich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast . The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment . The 1700-mg metformin dose had the most marked appetite suppressant action . Similarly , hunger ratings were significantly lowered after metformin , and the effect was most pronounced after the administration of 1700 mg of metformin . To assess the efficacy of metformin in reducing bodyweight , 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA ( American Diabetes Association ) diet before being r and omized to receive either metformin ( 850 mg ) or placebo twice daily in a double-blind fashion for 24 weeks . A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period . Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment ; their mean maximum weight loss was 8 kg greater than that of the placebo group , with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period . These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity OBJECTIVE To evaluate whether metformin , when added to a program of personal goal setting , improves weight loss and clinical status in obese adolescents . STUDY DESIGN In a r and omized double-blind placebo controlled trial , 85 adolescents with insulin resistance were r and omized to receive metformin ( 70 % ) or placebo ( 30 % ) , along with monthly goal setting for diet and exercise modification .  Anthropometric measures , fasting blood analysis , and glucose tolerance tests were performed at baseline and 6 months . RESULTS Mean age was 15.7 years . Mean body mass index ( BMI ) was 39.7 kg/m(2 ) . 71 % were female , 58 % were Hispanic , and 34 % were African-American . 76 % of participants completed the study . Goal setting alone did not result in significant weight loss . In addition , there were no group differences between metformin and placebo in weight loss or measures of glucose metabolism . However , among females taking metformin , there was a significant decrease in BMI not seen in the placebo group . Furthermore , metformin adherence , when accompanied by lifestyle change , was a predictor of BMI decrease of 5 % or more . 60 % of 10 subjects who adhered to metformin and decreased portion size decreased BMI by > 5 % . CONCLUSIONS In this group of predominately minority adolescents , monthly goal setting alone did not lead to weight loss . Although the addition of metformin had no effect on weight loss overall , the agent did significantly increase weight loss among females and weight loss was predicted by degree of metformin adherence . However , weight loss was only found in those participants also reporting lifestyle change , particularly a decrease in portion sizes . These results suggest that metformin may be a useful agent to promote short-term weight loss among girls making modest lifestyle changes CONTEXT Childhood obesity is increasingly associated with type 2 diabetes ( T2D ) . Metformin reduces the risk for T2D in adult obese nondiabetic patients , but the evidence in obese children and young people is inconclusive . OBJECTIVE The objective of the study was to assess the effect of metformin on body mass index sd score ( BMI -SDS ) , metabolic risk factors , and adipokines . DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . SETTING The study was conducted at six pediatric endocrine centers in the United Kingdom . PARTICIPANTS One hundred fifty-one obese children and young people with hyperinsulinemia and /or impaired fasting glucose or impaired glucose tolerance ( metformin : 74 , placebo : 77 ) . The study was comprised of 67.5 % females , 65.6 % postpubertal individuals , and 23.8 % British Asian or Afro-Caribbean participants . The age range was 8 - 18 yr , the mean age was 13.7 ( SD 2.3 ) yr , and the mean BMI -SDS was + 3.4 ( SD 0.5 ) . INTERVENTIONS The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months . MAIN OUTCOME MEASURE The main outcome measure was a reduction in BMI -SDS at 6 months . Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests , alanine aminotransferase ( ALT ) , and adiponectin to leptin ratio ( ALR ) at 3 and 6 months . RESULTS Metformin was associated with a significant reduction in BMI -SDS compared with placebo at 6 months [ mean difference -0.1 SD ( 95 % confidence interval -0.18 to -0.02 ) , P = 0.02 ] . Significant improvements at 3 months were found in the metformin group : fasting glucose , -0.16 mmol/liter ( -0.31 to -0.00 ) , P = 0.047 ; ALT , 19 % ( 5 - 36 % ) , P = 0.008 ; and ALR , 32 % ( 4 - 67 % ) , P = 0.02 . CONCLUSIONS Metformin therapy has a beneficial treatment effect over placebo for BMI -SDS , fasting glucose , ALT , and ALR ratio at 3 months , with changes in BMI -SDS sustained at 6 months OBJECTIVE To evaluate the effect of metformin treatment on the risperidone-induced body weight gain in patients . METHODS In a 12-weeks , double-blind , placebo controlled , r and omized trial between October 2006 and October 2007 which was conducted in the Child and Adolescent Psychiatric Consultation Center of Isfahan University of Medical Sciences , 49 patients were entered the study with schizophrenia diagnosis . Then metformin ( 500 mg bid ) or placebo was administrated with risperidone ( 6 mg ) for the patients . Weight , height , and body mass index BMI were measured at the beginning , at 4 weeks , and at 12 weeks of the study . Changes in weight and BMI were evaluated by using repeated measures analysis of variance . RESULTS Seventeen patients were excluded from the study . Repeated measure analysis of variances showed a significant difference between weight and BMI in both metformin ( p<0.001 , p<0.015 ) and placebo group ( p<0.013 , p<0.005 ) . CONCLUSION Metformin treatment did not show a significant effect to control the body weight of patients after 12 weeks BACKGROUND AND AIM Young women are at high risk of weight gain but few weight management interventions have been investigated in this group . This study aim ed to determine the effect of metformin on body weight , body composition , metabolic risk factors and reproductive hormone levels in overweight or obese young women compared to placebo and comprehensive lifestyle intervention . METHODS AND RESULTS 203 overweight or obese young women ( BMI 33.2+/-0.3 kg/m² , age 28+/-0.3 years ) were r and omised to 1500 mg/day metformin ( M ) plus general lifestyle advice , placebo ( P ) plus general lifestyle advice or comprehensive lifestyle intervention including structured diet , exercise and behavioural therapy ( L ) for 12-weeks . At 12-weeks , linear mixed models found that L group had greater weight loss ( -4.2+/-0.4 kg ) compared to M ( -1.0+/-0.4 kg ) and P groups ( -0.2+/-0.3 kg ) ( P < 0.0001 ) . Weight loss between M and P groups were not significantly different . Attrition rate was 48 % for L , 34 % for M and 29 % for P ( P = 0.08 ) . Intention-to-treat analysis showed that 10 % ( 8/79 ) of the subjects in P group had gained weight ( > 3 % ) , compared to 3 % ( 2/65 ) from M group and none ( 0/59 ) from L group ( P < 0.001 ) . The L group had the greatest decrease in waist circumference ( -5.2+/-0.7 cm ) and fat mass ( -5.4+/-0.7 kg ) compared to the other groups ( P < 0.05 ) . No significant time-by-group effects were seen in plasma lipids , SHBG , testosterone , blood pressure , serum folate , serum ferritin and serum vitamin B12 . CONCLUSION Lifestyle intervention was more effective in reducing body weight and improving body composition compared to metformin among healthy overweight or obese young women OBJECTIVE To study whether metformin reduces obesity , homeostasis model assessment for insulin resistance index ( HOMA-IR ) , and the metabolic syndrome ( MtS ) in obese European adolescents in addition to previous unsuccessful lifestyle intervention . DESIGN AND METHODS After 6 months of multiprofessional lifestyle intervention , 70 out of 86 adolescents without improvement in body mass index ( BMI ) and HOMA-IR  were r and omized into either the placebo ( n=34 ) or the metformin group ( 2 × 500 mg/day , n=36 ) in addition to ongoing lifestyle intervention for another 6 months . RESULTS Age was 13.8 years , BMI was 33.1 kg/m(2 ) , 65 % were female , and 89 % were Caucasians . During lifestyle intervention alone , BMI and HOMA-IR deteriorated significantly . In the subsequent medication period , HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups ( HOMA-IR decreased 73 vs 54 % respectively in metformin versus placebo ; P=0.048 ) , but BMI remained unchanged . The insulin sensitivity index , however , only improved in the metformin group . High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication . MtS remained unchanged . CONCLUSIONS Obese European adolescents '  insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention . Most differences did not reach statistical significance , probably due to improved compliance with lifestyle intervention as a placebo effect . In addition , the metformin dose may be too low CONTEXT Metformin therapy for adults and children with type 2 diabetes is well established . However , its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined . OBJECTIVE We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity . DESIGN AND SETTING Patients referred to a pediatric endocrine clinic were enrolled in a r and omized , double-blind , crossover trial . PATIENTS Twenty-eight patients ( 13 males ) aged 9 - 18 yr participated in the study . INTERVENTION Patients received metformin ( 1 g twice daily ) and placebo for 6 months , each with a 2-wk washout period . MAIN OUTCOME MEASURES Body composition ( anthropometry , dual-energy x-ray absorptiometry , and abdominal magnetic resonance imaging ) , and insulin sensitivity ( Si ; minimal model , fasting insulin and glucose ) were measured at baseline and 6 and 12 months . RESULTS Mean age of subjects at baseline was 12.5 + /- 2.2 yr , median body mass index z-score 2.54 ( range , 1.93 - 2.85 ) . Metformin had a greater treatment effect over placebo for weight ( -4.35 kg , P = 0.02 ) , body mass index ( -1.26 kg/m(2 ) , P = 0.002 ) , waist circumference ( -2.8 cm , P = 0.003 ) , sc abdominal adipose tissue ( -52.5 cm(2 ) , P = 0.002 ) , and fasting insulin ( -2.2 mU/liter , P = 0.011 ) . Si improved in 45 % of subjects while on metformin and 27 % of subjects while on placebo ( P = 0.21 ) . CONCLUSIONS Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin . Although improvement in Si was noted in many individuals , Si was a less useful parameter for analysis of group data , possibly because of effects of variable compliance and changing Si during puberty Background / Objectives Off-label metformin is nowadays frequently used for the treatment of obesity in adolescents . However , studies on long-term metformin treatment in adolescents with obesity are scarce . Therefore , an 18 month open label extension study following an 18 months r and omized placebo-controlled trial ( RCT ) on the efficacy , safety , and tolerability of metformin in adolescents with obesity and insulin resistance was performed . Subjects/ Methods After completion of the RCT , metformin was offered to all participants with a body mass index st and ard deviation score ( BMI -sds ) > 2.3 and Homeostasis Model Assessment for Insulin Resistance ( HOMA-IR ) ≥ 3.4 . Endpoints were change in BMI and HOMA-IR . Results Overall , 31/42 participants completed the extension study ( 74 % girls , median age 14.8 ( 11.6 – 17.9 ) , BMI 31.2 ( 22.3 – 45.1 ) , HOMA-IR 3.4 ( 0.2 – 8.8 ) ) . At start , 22/42 ( 52.4 % ) participants were eligible for metformin  of which 13 ( 59.0 % ) agreed with treatment . In participants who continued metformin , an increase was observed in BMI ( + 2.2 ( + 0.2 to + 9.0 ) ) and HOMA-IR ( + 13.7 ( + 1.6 to + 48.3 ) ) . In metformin naive participants , BMI stabilized after an initial decrease ( + 0.5 ( −2.1 to + 5.1 ) ) . For HOMA-IR , a decrease was observed ( −1.1 ( −4.6 to + 1.4 ) ) . Conclusion While metformin treatment in metformin naive participants seems to result in an initial decrease in BMI and HOMA-IR , there is no evidence for sustained effect after prolonged use in adolescents . Limited compliance and /or insufficient dose may explain the differences in long-term effects between adolescents and adults BACKGROUND Metformin has been proffered as a therapy for adolescent obesity , although long-term controlled studies have not been reported . OBJECTIVE To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release ( XR ) therapy will reduce body mass index ( BMI ) in obese adolescents , as compared with placebo . DESIGN Multicenter , r and omized , double-blind , placebo-controlled clinical trial . SETTING The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007 . PARTICIPANTS Obese ( BMI > or = 95th percentile ) adolescents ( aged 13 - 18 years ) were r and omly assigned to the intervention ( n = 39 ) or placebo groups . Intervention Following a 1-month run-in period , subjects following a lifestyle intervention program  were r and omized 1:1 to 48 weeks ' treatment with metformin hydrochloride XR , 2000 mg once daily , or an identical placebo . Subjects were monitored for an additional 48 weeks . Main Outcome Measure Change in BMI , adjusted for site , sex , race , ethnicity , and age and metformin vs placebo . RESULTS After 48 weeks , mean ( SE ) adjusted BMI increased 0.2 ( 0.5 ) in the placebo group and decreased 0.9 ( 0.5 ) in the metformin XR group ( P = .03 ) . This difference persisted for 12 to 24 weeks after cessation of treatment . No significant effects of metformin on body composition , abdominal fat , or insulin indices were observed . CONCLUSION Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program . TRIAL REGISTRATION clinical trials.gov Identifiers : NCT00209482 and NCT00120146 CONTEXT Metformin treatment of women with polycystic ovary syndrome ( PCOS ) is widespread , as determined by studies with diverse patient population s. No comparative examination of weight changes or metabolite responses to different doses has been reported . OBJECTIVE The aim of this study was to determine whether different doses of metformin ( 1500 or 2550 mg/d ) would have different effects on body weight , circulating hormones , markers of inflammation , and lipid profiles . DESIGN The study included prospect i ve cohorts r and omized to two doses of metformin . SETTING The study was performed at a university teaching hospital with patients from gynecology/endocrinology clinics . PATIENTS The patients studied were obese ( body mass index , 30 to < 37 kg/m2 ; n = 42 ) and morbidly obese ( body mass index , > or = 37 kg/m2 ; n = 41 ) women with PCOS . INTERVENTION Patients were r and omized to two doses of metformin , and parameters were assessed after 4 and 8 months . MAIN OUTCOME MEASURES The main outcome measures were changes in body mass , circulating hormones , markers of inflammation , and lipid profiles . RESULTS Intention to treat analyses showed significant weight loss in both dose groups . Only the obese subgroup showed a dose relationship ( 1.5 and 3.6 kg in 1500- and 2550-mg groups , respectively ; P = 0.04 ) . The morbidly obese group showed similar reductions ( 3.9 and 3.8 kg ) in both groups . Suppression of and rostenedione was significant with both metformin doses , but there was no clear dose relationship . Generally , beneficial changes in lipid profiles were not related to dose . CONCLUSION Weight loss is a feature of protracted metformin therapy in obese women with PCOS , with greater weight reduction potentially achievable with higher doses . Additional studies are required to determine whether other aspects of the disorder may benefit from the higher dose of metformin Abstract Aim This study was undertaken to determine whether metformin would ameliorate insulin resistance , reduce weight and waist circumference and improve lipids in obese , but not morbidly obese , euglycemic women . Methods Obese women ( body mass index ( BMI ) ≥ 30 and < 40 kg/m2 and /or waist circumference > 88 cm ) , aged 35–65 were r and omized ( 1:1 ) to metformin 850 mg or identical placebo , twice daily for 26 weeks . The primary outcome was the change in insulin resistance determined by the homeostasis model of assessment ( HOMA-IR ) . Secondary outcomes included fasting insulin , glucose , weight , waist circumference and BMI . Results Of the 125 women screened , 117 enrolled and 100 women , mean age 53 years , were included in the primary intention-to-treat analysis . Metformin result ed in statistically significant between-group difference in the change in HOMA-IR ( change in median − 0.04 vs. placebo + 0.1 , p = 0.018 ) and BMI ( mean change − 1.00 kg/m2 ; 95 % confidence interval ( CI ) 1.37 to − 0.62 vs. placebo mean change 0.00 ; 95 % CI − 0.29 to 0.28 , p < 0.001 ) . Statistically significant reductions in HbA1c ( p = 0.008 ) and fasting insulin ( p = 0.03 ) and a borderline decrease in high density lipoprotein cholesterol ( p = 0.07 ) were also observed for metformin , compared with placebo . No effects were seen for waist circumference , fasting glucose or other lipids . Conclusion Treatment of euglycemic , obese , middle-aged women  with metformin 1700 mg per day reduced insulin resistance and weight compared with placebo . Further studies are needed to determine whether the use of metformin will prevent the progression of insulin resistance to type 2 diabetes mellitus in obese women Overweight and obesity are strong and potentially modifiable risk factors for type 2 diabetes ( T2D ) . Prevention of T2D among persons with prediabetes is a public health priority , and weight loss plays a central role in efforts to prevent or delay the disease . Whereas excess body weight is strongly associated with insulin resistance and hyperglycemia , improved glycemia is readily noticeable when persons with overweight or obesity lose weight ; however , the health benefits of weight loss may last only when the initial weight loss persists over the long term ( 1 ) . There is clinical impetus to examine whether baseline demographic , psychosocial , or physiologic factors can help to identify more favorable long-term weight loss ( LTWL ) patterns , especially in the context of available treatments for diabetes prevention . R and omized controlled trials ( RCTs ) have shown efficacy of metformin , intensive lifestyle intervention ( ILS ) , or both in preventing or delaying onset of T2D among high-risk persons with overweight and obesity ( 2 , 3 ) . In the DPP ( Diabetes Prevention Program ) , metformin and ILS reduced risk for diabetes relative to placebo by 31 % and 58 % , respectively , over an average follow-up of 2.8 years ( 2 ) . Metformin and ILS were associated with average weight losses at 2.8 years of 2.1 and 5.6 kg , respectively , versus 0.1 kg with placebo ( 2 ) , and weight loss was the primary driver of diabetes prevention ( 4 , 5 ) . During long-term follow-up of DPP participants in its Outcomes Study ( DPPOS ) , weight changes differed among treatment groups at 10 and 15 years ( 6 , 7 ) . After achieving significantly greater initial weight loss than participants in the other groups , those in the ILS group regained about 3.5 kg over time , with a net loss of about 2 kg relative to baseline at 10 years . However , those in the metformin group achieved and maintained an average loss of about 2.5 kg , and the average weight of those in the placebo group changed by 1 kg or less during the same period ( 6 ) . The DPP and the DPPOS make up the largest and longest clinical trial of metformin for prevention of T2D . In the DPP , weight loss explained 64 % of the beneficial effect of metformin on T2D risk ( 4 ) . The primary aims of the current study were to compare differences in LTWL maintenance by original intervention group among participants who achieved clinical ly significant weight loss of at least 5 % at 1 year and to examine baseline factors that predicted maintenance of weight loss for up to 15 years . We also evaluated the effect of postbaseline factors , such as degree of initial weight loss and adherence to the r and omized interventions . Methods The DPP ( July 1996 to July 2001 ) was an RCT that compared the efficacy of ILS , metformin , and placebo in prevention of T2D among 3234 participants with elevated glucose levels and overweight or obesity . The 1997 diagnostic criteria of the American Diabetes Association ( 8) were used to establish the primary outcome of diabetes , defined as a fasting plasma glucose level of 7.0 mmol/L ( 126 mg/dL ) or higher measured semiannually or a 2-hour plasma glucose level of 11.1 mmol/L ( 200 mg/dL ) or higher after a 75-g oral glucose load measured annually , with confirmation within 6 weeks . The protocol , baseline characteristics of the sample , and primary outcomes ( including all clinical and physiologic variables examined in these analyses ) have been described previously ( 2 , 9 , 10 ) , along with minor variations in eligibility criteria . Participants were r and omly assigned to receive an individually administered ILS ( a 16-session behavior modification intervention implemented over approximately 6 to 8 months , with a goal of achieving 7 % weight loss through healthy dietary changes , reductions in intake of calories and fat , and 150 minutes of moderate-intensity physical activity [ mostly walking ] per week ) , metformin ( 850 mg twice daily ) , or placebo ( 11 ) . Both medication interventions were masked ( double-blind ) , but the ILS was not . After 6 months , participants in the ILS group continued to receive individual and group reinforcement of the behavioral intervention at least every 2 months , regardless of diabetes status , but they were referred to their primary care provider ( PCP ) for diabetes management . Those in the metformin and placebo groups continued to receive the study drug until their plasma glucose level increased to 7.8 mmol/L ( 140 mg/dL ) or higher , at which time use of the study drug was discontinued and diabetes management was transferred to their PCP . The DPP study protocol was modified in July 2001 after an average follow-up of 3.2 years . Participants were informed of the main results , and there was a 1- to 2-week metformin and placebo washout period to identify whether a short-term drug effect accounted for the diabetes risk reduction with metformin ( 12 ) . The bridge protocol ( 1 August 2001 to 31 August 2002 ) was the 13-month period between the end of the DPP and the start of long-term follow-up ( DPPOS ) . Because efficacy was established for ILS compared with metformin and placebo in the cumulative reduction in diabetes incidence during the first 3.2 years , participants in all 3 groups were offered a group-administered version of the 16-session ILS . The group intervention , which had similar content but did not include individualized problem-solving and behavior changesupport components , was implemented over a 6-month period and was usually administered by the original staff . Rates of attendance at 1 or more sessions varied by group ( 58 % in the metformin group , 40 % in the ILS group , and 57 % in the placebo group ) ( 13 ) . The DPPOS began in September 2002 and examined 2779 ( 88.5 % ) of the remaining DPP participants for diabetes incidence and development of diabetes-related complications . Although the DPPOS is ongoing , the current analysis is based on average follow-up of 15 years from baseline of the DPP using data collected annually through 2013 ( Appendix Figure 1 ) . Similar proportions of the 3 r and omized DPP groups enrolled in the DPPOS ( 6 ) . During the DPPOS , metformin was provided to the group originally assigned to it , but without masking . In addition , when hemoglobin A1c levels reached 7 % or higher , use of study metformin was discontinued and diabetes care and medication management were transferred to the participant 's PCP ( this often included prescription of metformin by the PCP ) . In the ILS and placebo groups , all diabetes care and medication management were provided by the participant 's PCP .  Metformin  use was recorded at all visits for all participants during the DPP and the DPPOS . During the DPPOS , all 3 groups were offered educational lifestyle classes 4 times per year . Twice a year , the original ILS group was offered 2 to 4 booster sessions design ed to reinforce self-management behaviors for weight and activity . Lifestyle class attendance among the groups did not exceed 20 % for any of the sessions offered during the DPPOS ( data not shown ) . In all trial phases , written informed consent was obtained from all participants and studies were approved by each center 's institutional review board . An independent data and safety monitoring board appointed by the study sponsor ( the National Institute of Diabetes and Digestive and Kidney Diseases ) oversaw the studies . Appendix Figure 1 . DPP and DPPOS study design . DPP = Diabetes Prevention Program ; DPPOS = Diabetes Prevention Program Outcomes Study . Statistical Analysis Long-term weight loss was defined at each annual examination after the first year as weight loss of at least 5 % relative to baseline . We used fixed-effects models with the assumption of normally distributed errors to estimate the percentage of weight lost over time ( SAS Proc MIXED ) and generalized estimating equation ( GEE ) models to estimate the percentage of participants with LTWL ( SAS Proc GENMOD ) among those who lost at least 5 % in the first year ( 14 ) . The fixed-effects models used a compound symmetry correlation , and the GEE models used a logit link with an exchangeable correlation structure . The primary aim was to evaluate baseline and postr and omization predictors of maintenance of weight loss among participants who achieved clinical ly significant weight loss of at least 5 % at 1 year after r and omization . Potential predictors of LTWL include the baseline variables listed in the Appendix Table as well as postr and omization measures of percentage of weight lost in the first year , meeting the ILS exercise goal at the end of the core 16-session curriculum , meeting the ILS weight loss goal of 7 % at the end of the core curriculum , total number of ILS sessions , use of PCP-prescribed metformin or study metformin at the annual visit , and diabetes status at the annual visit . Appendix Table . Baseline Characteristics of Participants With < 5 % Versus 5 % Weight Loss in the First Year Two statistical methods were used to examine predictors of LTWL . First , we used logistic regression models to evaluate potential predictors of medium-term ( 5 years ) , long-term ( 10 years ) , and very-long-term ( 15 years ) weight loss ( SAS Proc LOGISTIC ) . Second , we used GEE models ( 15 , 16 ) to examine potential predictors of LTWL across all follow-up years . The GEE models provided an average estimate of the effect of the predictor on LTWL over the course of the study ( SAS Proc GENMOD ) and used a logit link and an independent correlation to ensure proper parameter estimation ( 17 ) . For both approaches , univariate models were developed separately for each predictor variable . Multivariate models included variables that were significant ( P < 0.05 ) predictors of LTWL in the univariate analyses . Final models included only measures that remained significant in the multivariate model . Given the wide variation in the numbers of participants achieving and maintaining weight loss of at least 5 % among the intervention groups , analyses were performed within groups . The incidence of diabetes diagnosed at any time in the DPP and the DPPOS was compared between participants 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 Previous observational studies have suggested that metformin  in diabetes patients may reduce breast cancer risk more than the reductions from other anti-diabetes medications . This r and omized , double-blind , placebo-controlled trial was performed to evaluate the efficacy of metformin for controlling physical and metabolic profiles related to prognosis and adverse events in non-diabetic breast cancer patients . Female breast cancer patients ( N = 105 ) , at least 6 months post-mastectomy , with obesity ( ≥25 kg/m2 ) and /or pre-diabetes ( fasting blood sugar levels ≥100 mg/dL ) , were r and omly assigned to three groups ( placebo , metformin 500 mg , and metformin 1000 mg ) stratified by tamoxifen use . A linear mixed model for repeated measurements among three groups and ANOVA for profile differences during 6 months of treatment were used for the intention-to-treat analysis . The metformin 1000 mg group had a significantly greater decline in glucose and HbA1c levels between treatment weeks 0 and 6 month ( p = 0.008 and 0.009 , respectively ) , and the declines increased with an increase in body mass index ( BMI ) level ( p interaction with BMI = 0.007 and 0.067 , respectively ) . A marginally significant different effect from the metformin 1000 mg treatment was detected for glucose and HbA1c levels ( p interaction = 0.084 and 0.063 , respectively ) in the intention-to-treat analysis . Metformin 1000 mg treatment had a favorable effect on controlling glucose and HbA1C levels in obese non-diabetic breast cancer patients , indicating prognostic importance . Further trials are needed to eluci date the risk – benefit ratio of long-term use of metformin Background The efficacy of pharmacological treatment in controlling  childhood obesity  is controversial . We aim ed to compare the effects of three types of drug regimens and placebo on generalized and abdominal obesity among obese children and adolescents who did not succeed to lose weight 3 months after lifestyle modification ( diet and exercise ) . Methods This triple-masked r and omized clinical trial was conducted among 180 participants aged 10–16 years . They were assigned r and omly to 4 groups of equal number to receive metformin , fluoxetine , a combination of the two drugs , or placebo . The trial lasted for 12 weeks and participants were followed up for an additional 12-week period . Results Overall , 91.1 % ( n=164 ) of the enrolled participants completed the trial . After the 12-week trial , the body mass index decreased significantly in all groups receiving medications [ approximately −1.2 ( 0.2 ) kg/m2 , P<0.05 ] . This decrease was not significant in the placebo group . Waist circumference decreased significantly in the groups receiving metformin [ −2.1 ( 0.4 ) cm , P=0.03 ) ] as well as in the group receiving a combination therapy of metformin and fluoxetine [ −2.5 ( 0.4 ) cm , P=0.01 ) ] . In the 24-week follow-up study , these anthropometric indexes were lower than the baseline in the group that had received a combination therapy of metformin and fluoxetine . No serious drug side-effects were reported . Conclusions A limited period of such treatment may help weight control , and might be used to encourage those children who have been refractory to weight loss for continuing the non-pharmacological programs . Our findings should be confirmed in future studies with a longer follow-up period 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 Background : As adolescents with obesity and insulin resistance may be refractory to lifestyle intervention therapy alone , additional off-label metformin therapy is often used . In this study , the long-term efficacy and safety of metformin versus placebo in adolescents with obesity and insulin resistance is studied . Methods : In a r and omized placebo-controlled double-blinded trial , 62 adolescents with obesity aged 10–16 years old with insulin resistance received 2000 mg of metformin or placebo daily and physical training twice weekly over 18 months . Primary end points were change in body mass index ( BMI ) and insulin resistance measured by the Homeostasis Model Assessment for Insulin Resistance ( HOMA-IR ) . Secondary end points were safety and tolerability of metformin . Other end points were body fat percentage and HbA1c . Results : Forty-two participants completed the 18-month study ( 66 % girls , median age 13 ( 12–15 ) years , BMI 30.0 ( 28.3 to 35.0 ) kg m−2 and HOMA-IR 4.08 ( 2.40 to 5.88 ) ) . Median Δ BMI was + 0.2 ( −2.9 to 1.3 ) kg m−2 ( metformin ) versus + 1.2 ( −0.3 to 2.4 ) kg m−2 ( placebo ) ( P=0.015 ) . No significant difference was observed for HOMA-IR . No serious adverse events were reported . Median change in fat percentage was −3.1 ( −4.8 to 0.3 ) versus −0.8 ( −3.2 to 1.6)% ( P=0.150 ) , in fat mass −0.2 ( −5.2 to 2.1 ) versus + 2.0 ( 1.2–6.4 ) kg ( P=0.007 ) , in fat-free mass + 2.0 ( −0.1 to 4.0 ) versus + 4.5 ( 1.3 to 11.6 ) kg ( P=0.047 ) and in ΔHbA1c + 1.0 ( −1.0 to 2.3 ) versus + 3.0 ( 0.0 to 5.0 ) mmol mol−1 ( P=0.020 ) ( metformin versus placebo ) . Conclusions : Long-term treatment with metformin in adolescents with obesity and insulin resistance results in stabilization of BMI and improved body composition compared with placebo . Therefore , metformin may be useful as an additional therapy in combination with lifestyle intervention in adolescents with obesity and insulin resistance
Network meta- analysis revealed that in adolescents , intervention with 2000 mg/day metformin ranked better than other interventions ; however , 1000 mg/day metformin for 3 months may be most suitable for adolescents .
For adults , metformin at doses of 3000 and 1000 mg/day ranked the highest , other than minimeal and lifestyle interventions ; moreover , intervention with 3000 mg/day for 6 months and 1000 mg/day for 0.5 months may be suitable for adults .
Conclusion When considering the efficacy of interventions for losing weight , metformin offers clear advantages for overweight and obese population
Purpose Our aim was to assess the efficacy of metformin for weight loss in overweight and obese people through a systematic review and network meta- analysis and to identify the most suitable dosage and intervention period for using metformin  in adolescents and adults .