title: The Effects of Metformin on Body Mass Index and Glucose Tolerance in Obese Adolescents With Fasting Hyperinsulinemia and a Family History of Type 2 Diabetes Enhancing treatment of obesity by using a distracting mini-meal: a new approach to an old problem Metformin-based treatment for obesity-related hypertension: a randomized, double-blind, placebo-controlled trial Metformin in combination with structured lifestyle intervention improved body mass index in obese adolescents, but did not improve insulin resistance Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. Combination of direct and indirect evidence in mixed treatment comparisons. Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children Metformin treatment leads to an increase in basal, but not insulin-stimulated, glucose disposal in obese patients with impaired glucose tolerance. Treatment with metformin of non-diabetic men with hypertension, hypertriglyceridaemia and central fat distribution: the BIGPRO 1.2 trial. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity Effect of metformin on glucagon-like peptide 1 (GLP-1) and leptin levels in obese nondiabetic subjects. Effect of metformin on patients with impaired glucose tolerance. Metformin use in children with obesity and normal glucose tolerance – effects on cardiovascular markers and intrahepatic fat Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. The effects of metformin on inflammatory mediators in obese adolescents with insulin resistance: controlled randomized clinical trial GRADE guidelines: 3. Rating the quality of evidence. Metformin for overweight women at midlife: a double-blind, randomized, controlled trial Metformin decreases plasma resistin concentrations in pediatric patients with impaired glucose tolerance: a placebo-controlled randomized clinical trial. Lifestyle intervention improves fitness independent of metformin in obese adolescents. Metformin in obese children and adolescents: the MOCA trial. Efficacy and Safety of Linagliptin Co-Administered with Low-Dose Metformin Once Daily Versus High-Dose Metformin Twice Daily in Treatment-Naïve Patients with Type 2 Diabetes: a Double-Blind Randomized Trial Reliability of the PEDro scale for rating quality of randomized controlled trials. The effect of comprehensive lifestyle intervention or metformin on obesity in young women. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Effect of metformin on food intake in obese subjects. Effect of metformin vs. placebo treatment on serum fatty acids in non-diabetic obese insulin resistant individuals. Effects of metformin on the body composition in subjects with risk factors for type 2 diabetes. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.
abstract: 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 OBJECTIVE The management of obesity , apart from exercise , mainly involves a calorie restriction regimen . A pharmaceutical treatment is often used to improve patient compliance and diet effectiveness , although several side-effects have previously been described . To improve patient compliance and diet effectiveness without incurring unpleasant side-effects , we evaluated whether a distracting mini-meal can physiologically decrease the absorption of fats and carbohydrates . DESIGN Two minutes before each of the three meals consumed daily , 32 obese patients were treated with a distracting mini-meal , 32 with metformin , and 32 with placebo . At baseline and after 1 , 3 , and 6 months of treatment , body weight , body mass index , waist circumference , fasting/post-pr and ial insulinaemia and glycaemia , homeostasis model assessment -index , triacylglycerols , and total cholesterol were evaluated . RESULTS All patients showed good compliance . With the exception of post-pr and ial glycaemia , a significant reduction in all parameters was documented in every group , albeit the greater variation was observed in patients treated with a distracting mini-meal or metformin . No one showed noteworthy side-effects . CONCLUSIONS Our study focuses on a distracting mini-meal that could become a useful tool in enhancing weight loss . The beneficial effect of a distracting meal on insulin resistance , glucose , and lipid metabolism suggest its possible use to prevent or mitigate obesity-related disorders Objectives : Obesity and hypertension are associated with an adverse metabolic profile and systemic low- grade inflammation . Metformin reduces weight and inflammation in patients with diabetes , but it is unclear whether it has beneficial effects in patients without diabetes . The objective was to explore whether metformin-based treatment could benefit obesity-related hypertension without diabetes . Methods : A r and omized , double-blind , placebo-controlled factorial trial was conducted in 360 obese hypertensive patients without diabetes in Chongqing , China . After a 1–2-week run-in period , patients were r and omly assigned to metformin ( 500 mg once per day ) or placebo , as well as to an antihypertensive medication .  Change in blood pressure , obesity measurements and metabolic profile were assessed at 24 weeks . Results : The 180 participants r and omized to metformin and 180 r and omized to placebo were similar at baseline . At 24 weeks , metformin compared with placebo did not have significant effects on blood pressure , blood glucose , high-density or low-density lipoprotein cholesterol , but it did reduce total serum cholesterol ( 0.27mmol/l , P = 0.038 ) . Metformin also significantly reduced weight ( −0.7 kg , P = 0.006 ) , BMI ( −0.2 kg/m2 , P = 0.024 ) , waist circumference ( −0.9 cm , P = 0.008 ) , and both subcutaneous ( −6.1 cm2 , P = 0.043 ) and visceral adiposity ( −5.4 cm2 , P = 0.028 ) as measured by computed tomography , and lowered serum high-sensitivity C-reactive protein levels ( −0.6 mg/dl , P < 0.001 ) . There was no significant difference in adverse events ( P = 0.785 ) . Conclusions : Metformin has no effect on blood pressure and blood glucose levels , but it does reduce total cholesterol , abdominal obesity and C-reactive protein levels in obese hypertensive patients without diabetes 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 : To study the long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance . Patients : 181 African American subjects with insulin resistance and normal glucose tolerance test were r and omised to receive glipizide 5 mg/day ( n = 25 ) , metformin 500 mg/day ( n = 59 ) , or placebo ( n = 97 ) for 24 months . Insulin sensitivity , glucose tolerance , lipid profile , left ventricular mass ( echocardiography ) , aortic distensibility ( echocardiography , blood pressure ) , aortic pulse wave velocity ( PWV , carotid to femoral artery , Doppler ) were measured at baseline and at 12 and 24 months after r and omisation . Results : A significant increase in PWV was observed in both glipizide ( mean ( SEM ) change at 24 months 2.8 ( 2.7 ) m/s , p = 0.012 ) and metformin ( 2.2 ( 0.7 ) m/s , p = 0.01 ) groups during the follow up period . In contrast , PWV remained unchanged in the placebo group . The increase in PWV in the treatment groups was significant compared with placebo ( analysis of variance p < 0.05 ) . Other cardiovascular or metabolic variables did not change significantly compared with placebo during follow up . Conclusions : The observed increase in PWV is consistent with a decrease in the elastic properties of the aorta . The use of oral antidiabetic agents for the prevention of cardiovascular complications in non-diabetic African Americans with insulin resistance needs to be critically evaluated Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome ( PCOS ) . Dietary-induced weight loss and the administration of insulin-lowering drugs , such as metformin , are usually followed by improved hyper and rogenism and related clinical abnormalities . This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight , fat distribution , the glucose-insulin system , and hormones in a group of 20 obese PCOS women [ body mass index ( BMI ) > 28 kg/m2 ] with the abdominal phenotype ( waist to hip ratio > 0.80 ) , and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS . At baseline , we measured sex hormone , sex hormone-binding globulin ( SHBG ) , and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography ( CT ) at the L4-L5 level , to measure sc adipose tissue area ( SAT ) and visceral adipose tissue area . All women were then given a low-calorie diet ( 1,200 - 1,400 kcal/day ) alone for one month , after which anthropometric parameters and CT scan were newly measured . While continuing dietary treatment , PCOS women and obese controls were subsequently placed , in a r and om order , on metformin ( 850 mg/os , twice daily ) ( 12 and 8 , respectively ) or placebo ( 8 and 12 , respectively ) , according to a double-blind design , for the following 6 months . Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment . During the treatment period , 3 women of the control group ( all treated with placebo ) were excluded because of noncompliance ; and 2 PCOS women , both treated with metformin , were also excluded because they became pregnant . Therefore , the women cohort available for final statistical analysis included 18 PCOS ( 10 treated with metformin and 8 with placebo ) and 17 control women ( 8 treated with metformin and 9 with placebo )  . The treatment was well tolerated . In the PCOS group , metformin therapy improved hirsutism and menstrual cycles significantly more than placebo .  Baseline anthropometric and CT parameters were similar in all groups . Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups , without any significant effect on CT scan parameters . In both PCOS and control women , however , metformin treatment reduced body weight and BMI significantly more than placebo . Changes in the waist-to-hip ratio values were similar in PCOS women and controls , regardless of pharmacological treatment . Metformin treatment significantly decreased SAT values in both PCOS and control groups , although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment . On the contrary , visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups , but only in the former was the effect of metformin treatment significantly higher than that of placebo .  Fasting insulin significantly decreased in both PCOS women and controls , regardless of treatment , whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin . Neither metformin or placebo significantly modified the levels of LH , FSH , dehydroepi and rosterone sulphate , and progesterone in any group , whereas testosterone concentrations decreased only in PCOS women treated with metformin .  SHBG concentrations remained unchanged in all PCOS women ; whereas in the control group , they significantly increased after both metformin and placebo .  Leptin levels decreased only during metformin treatment in both PCOS and control groups . ( ABSTRACT TRUNCATED Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed 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 This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations . METHODS Nineteen obese patients with impaired glucose tolerance ( IGT ) were treated with either metformin or placebo in a r and omized , double-blind , placebo-controlled , cross-over study . Insulin secretion and insulin resistance were quantified using the homeostasis model assessment ( HOMA ) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose ( SSPG ) . RESULTS The average benefit of metformin was 0.6 mmol/l for glucose ( 95 % confidence interval ( CI ) 0.2 - 0.9 P = 0.002 ) , 2.8 pmol/l for insulin ( 95 % CI 0.2 - 5.4 , P = 0.019 ) . Insulin resistance , as quantified by HOMA , was improved by 1.1 ( 95 % CI 0.2 - 2.0 , P = 0.004 ) , without any change in insulin secretion . Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period , as was the SSPG concentration . However , both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo . CONCLUSIONS These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure . In contrast , neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia BACKGROUND In the BIGPRO 1 trial , one year of treatment with metformin in non-diabetic obese subjects with a central fat distribution had no significant effect on fasting plasma triglyceride concentration or on blood pressure despite a decrease in weight , fasting plasma insulin and glucose concentrations . To re-evaluate the effect of metformin on fasting triglyceride concentration and on blood pressure , the BIGPRO 1.2 trial included non-diabetic men ( n=168 ) with a fasting plasma triglyceride concentration > or = 1.7 and < or = 6.5 mmol/l , high blood pressure ( systolic > or = 140 and < or = 180 and /or diastolic > or = 90 and < or = 105 mmHg , or treatment for hypertension ) and a waist-to-hip ratio > or = 0.95 . METHODS A r and omised double-blind trial comparing metformin treatment ( 850 mg bid ) with placebo . RESULTS Metformin had no significant effect either on blood pressure or plasma triglyceride concentration . In comparison with the placebo group , fasting plasma insulin ( p<0.04 ) , total cholesterol ( p<0.05 ) and Apo B ( p<0.008 ) concentrations decreased more in the metformin group in the BIGPRO 1 . 2 trial , confirming most of the previous results of the BIGPRO 1 trial . Tissue plasminogen activator antigen concentration decreased significantly ( p<0.01 ) only in the metformin group , but this was not significantly different from the placebo group ( p<0.12 ) ; further , there were no significant differences in the change in plasminogen activator inhibitor 1 . CONCLUSIONS The consistency of the two BIGPRO trials supports the conclusion that metformin affects several cardiovascular risk factors favourably in non-diabetic subjects with a central fat distribution 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 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 To evaluate the effects of metformin on glucagon-like peptide 1 ( GLP-1 ) and leptin levels . RESEARCH DESIGN AND METHODS A total of 10 obese nondiabetic male patients were studied before and after a 14-day treatment with 2,550 mg/day metformin and were compared with 10 untreated obese control subjects . On days 0 and 15 , leptin and GLP-1(7 - 36)amide/(7 - 37 ) levels were assessed before and after an oral glucose load during a euglycemic hyperinsulinemic clamp to avoid the interference of variations of insulinemia and glycemia on GLP-1 and leptin secretion . The effects of metformin on GLP-1(7 - 36)amide degradation in human plasma and in a buffer solution containing dipeptidyl peptidase IV ( DPP-IV ) were also studied . RESULTS Leptin levels were not affected by the oral glucose load , and they were not modified after metformin treatment . Metformin induced a significant ( P < 0.05 ) increase of GLP-1(7 - 36)amide/(7 - 37 ) at 30 and 60 min after the oral glucose load ( 63.8 + /- 29.0 vs. 50.3 + /- 15.6 pmol/l and 75.8 + /- 35.4 vs. 46.9 + /- 20.0 pmol/l , respectively ) , without affecting baseline GLP-1 levels . No variations of GLP-1 levels were observed in the control group . In pooled human plasma , metformin ( 0.1 - 0.5 microg/ml ) significantly inhibited degradation of GLP-1(7 - 36)amide after a 30-min incubation at 37 degrees C ; similar results were obtained in a buffer solution containing DPP-IV . CONCLUSIONS Metformin significantly increases GLP-1 levels after an oral glucose load in obese nondiabetic subjects ; this effect could be due to an inhibition of GLP-1 degradation AIMS To evaluate the effect of metformin on glucose metabolism , insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance ( IGT ) . METHODS Seventy subjects with IGT were r and omized under double-blind conditions to receive either placebo ( n = 37 ) or metformin ( n = 33 ) at a dosage of 250 mg three times daily for a duration of 12 months . Glycaemic control , plasma insulin and other biochemical indexes were assessed before and after 3 , 6 and 12 months . RESULT At 12 months the conversion rate to diabetes was 16.2 % in the placebo group compared to 3.0 % for the metformin group ( P = 0.011 ) . Of subjects treated with metformin for 12 months , 84.9 % became normoglycaemic compared to 51.4 % of those receiving the placebo . Significant improvements in fasting glucose , glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessment s. CONCLUSIONS Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects Abstract Objective : To determine if metformin improves markers of inflammation , thrombosis , and intrahepatic fat contents in children with uncomplicated obesity . Methods : Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein ( hsCRP ) and /or fibrinogen concentrations ( > 2 st and ard deviations ) were r and omized to structured diet/exercise or diet/exercise and metformin for 6 months . Blood sample s , dual energy X-ray absorptiometry data , and liver magnetic resonance images were obtained . Results : Forty-two of 66 recruited children ( 7–18 years ) completed 6 months . Weight loss was modest but more pronounced in the metformin group ( –4.9±1.0 kg ) than in the diet/exercise group ( –1.7±1.1 kg , p<0.03 ) , whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group . Baseline intrahepatic fat was high but decreased only in the diet/exercise ( not metformin ) pubertal group . Conclusions : Six months of metformin therapy improved weight loss and reduced abdominal adiposity , but did not enhance the beneficial effect of diet and exercise on markers related to inflammation , thrombosis , or hepatic fat in obese children with normal glucose tolerance The presence of fatty liver per ultrasound and liver-associated enzymes were measured in a select cohort of youth with both obesity and insulin resistance , and the effect of metformin on these parameters evaluated . Fifty obese , multiethnic , insulin-resistant adolescents ( mean age 15.1 yr , mean body mass index 39.8 kg/m2 ) were r and omized to receive lifestyle recommendations plus either twice per day doses of 850 mg of metformin or placebo .  Fasting and post-glucose challenge biochemistries and liver ultrasounds were compared at baseline and 6 months . The prevalence of fatty liver was 74 % , elevated alanine aminotransferase ( ALT ) 14 % , aspartate aminotransferase ( AST ) 14 % , and gamma-glutamyl transferase ( GGT ) 17 % . Fatty liver was mild in 23 % , moderate in 31 % , and severe in 46 % . Fatty liver was more common in male and Hispanic subjects and elevated ALT more common in Hispanic subjects . Subjects with fatty liver appeared more insulin resistant ( higher fasting insulin and triglycerides , lower high-density lipoprotein cholesterol ) and had higher ALT and AST . At 6 months , mean ALT , GGT , and fasting insulin improved significantly in all subjects . Fatty liver prevalence ( p < 0.04 ) , severity ( p < 0.04 ) , and fasting insulin ( p < 0.025 ) improved significantly with metformin compared to placebo . Non-alcoholic fatty liver disease ( NAFLD ) occurs with a high prevalence and severity in obese , insulin-resistant adolescents . While metformin plus lifestyle intervention appears promising , defining NAFLD therapies capable of preventing fibrosis and cirrhosis requires further study Abstract Objective : To compare serum concentrations of inflammatory cytokines , interleukin 6 ( IL-6 ) , high-sensitivity C-reactive protein ( hs-CRP ) , adiponectin , and tumor necrosis factor α ( TNFα ) , before and after 3 months treatment with metformin in obese adolescents with insulin resistance ( IR ) . Design and subjects : This was a r and omized , double-blinded , clinical trial of two groups of obese adolescents with IR , aged 9–18 years : a placebo group ( n=14 ) and a metformin group ( n=12 ) who received 500 mg metformin every 12 h for 3 months  . Anthropometric and biochemical ( metabolic and inflammatory cytokines ) assessment s were compared at the beginning and end of treatment . Results : After 3 months of treatment , body mass index ( kg/m2 ) was reduced in both groups : placebo group ( 32.82±6.37–32.10±6.52 ; p=0.011 ) and metformin group ( 33.44±5.82–32.71±5.77 ; p=0.015 ) . Serum fasting insulin concentrations ( pmol/L ) increased in the placebo group ( 189.45±112.64–266.06±167.79 ; p=0.01 ) and showed a slight decrease in the metformin group ( 256.82±113.89–229.25±86.53 ; p=0.64 ) . Adiponectin concentrations ( μg/mL ) decreased in the placebo group ( 13.17±7.31–5.65±6.69 ; p=0.02 ) , while these remained stable in the metformin group ( 8.57±3.98–7.86±6.23 ; p=0.64 ) . In the metformin group , significant reductions were found in the variances of serum TNFα concentrations ( p=0.006 ; Levene test ) . Conclusion : These results suggest that treating obese adolescents with IR  using metformin for 3 months is an option for patients without response to traditional lifestyle change because metformin improves inflammatory activity , which is an etiological factor in cardiovascular disease development This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence 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 The objective was to determine the effect of metformin on the concentrations of resistin and other markers of insulin resistance or inflammation ( C-reactive protein , cytokines , body weight , HbA1c , among others ) in minors with glucose intolerance . Patients aged 4 to 17 years with glucose intolerance were studied . They were r and omized to receive 850 mg of either metformin or placebo twice daily for 12 weeks , during which all followed an iso-caloric diet and an exercise program .  High sensitivity C-reactive protein , TNF-alpha , IL-6 , IL1-beta , resistin , leptin , adiponectin , glucose , insulin , HbA1c , lipid profile and transaminases were measured at the beginning and at the end of the period . Fifty-two patients were included , 11.9±2.6 years old ; 28 ( 12 males/16 females ) received metformin and 24 placebo ( 11 males/13 females ) . Baseline characteristics were similar between groups ( except for body mass index , which in the metformin group was slightly higher ) . Percentage weight loss was greater in the metformin group ( -5.86 % vs 2.75 % , P<.05 ) . At study end , there were statistically significant differences in resistin concentrations , even after adjusting for confounding variables ( F=7.714 ; P<.006 ) . Also , metformin was associated with a significant decrease in HOMA-IR index ( P=.032 ) and HbA1c levels ( P=.001 ) , but no change was observed in the concentration of other markers of inflammation . Metformin result ed in significant reductions of plasma resistin levels in minors with glucose intolerance . This change is independent of its effects on body weight . In contrast , metformin did not alter the concentration of inflammatory markers PURPOSE Obesity in adolescence increases the risk for early adult cardiovascular disease . We recently showed that 6 months of diet , exercise , and metformin result ed in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity . The purpose of the present study was to determine whether changes in cardiorespiratory fitness ( CRF ) after 6 months of structured diet and exercise ( DE ) or DE plus metformin are related to the previously observed changes in adiposity , markers of inflammation , and intrahepatic fat . METHODS Sixteen obese pubertal adolescents between the ages of 10 and 17 were r and omized into a structured lifestyle program consisting of DE or DE plus metformin . Subjects performed aerobic and resistance exercise 3 d·wk⁻¹ , 30 min per session . Cycle ergometer maximal oxygen consumption ( V˙O2max ) , body composition , blood markers ( glucose , insulin , homeostatic model assessment -insulin resistance , interleukin-6 , hsCRP ) , and intrahepatic fat were measured at baseline and 6 months . RESULTS In the cohort , as whole-body weight decreased by 4.0 % ( P = 0.009 ) , body mass index decreased by 4.9 % ( P = 0.003 ) , percent body fat decreased by 8.8 % ( P < 0.001 ) , and V˙O2max improved in 10 of 16 subjects . The addition of metformin provided no further effect on body composition , CRF , or inflammatory factors . More favorable changes in adiposity , adiponectin , and a trend toward blood glucose and interleukin-6 concentrations ( P = 0.07 ) were observed in subjects who increased V˙O2max at 6 months ( n = 10 ) compared with no change in these variables in those who did not improve V˙O2max . CONCLUSIONS Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents .  Improvements in V˙O2max seem to be associated with more favorable metabolic outcomes 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 Introduction The aim of this study was to investigate the efficacy and safety of linagliptin + low-dose ( LD ) metformin once daily versus high-dose ( HD ) metformin twice daily in treatment-naïve patients with type 2 diabetes . Methods Patients ( n = 689 ) were r and omized ( 1:1 ) to double-blind treatment with linagliptin 5 mg + LD metformin ( 1000 mg ) or HD metformin ( 2000 mg ) for 14 weeks . Metformin was initiated at 500 mg/day and up-titrated within 2 weeks ; the dose then remained unchanged . The primary endpoint was change in glycated hemoglobin ( HbA1c ) from baseline to Week 14 in patients who tolerated a daily metformin dose of ≥1000 mg after 2 weeks . Results At Week 14 , HbA1c changed from a mean baseline of 8.0 % ( 64 mmol/mol ) by −0.99 % ( −11 mmol/mol ) for linagliptin + LD metformin , and −0.98 % ( −11 mmol/mol ) for HD metformin [ treatment difference −0.01 % ( 95 % confidence interval −0.13 , 0.12 ) ( 0 mmol/mol ) , P = 0.8924 ] . The proportion of patients who achieved HbA1c < 7.0 % ( 53 mmol/mol ) without occurrence of moderate or severe gastrointestinal ( GI ) events ( including abdominal pain , nausea , vomiting , diarrhea , and decreased appetite ) was the same in both groups ( 51.3 % for both ) . Although the occurrence of moderate or severe GI events was similar , the linagliptin + LD metformin group had fewer mild GI events ( 18.5 % versus 24.3 % ) . The incidence of hypoglycemia was low in both groups . Conclusion Linagliptin + LD metformin combination showed similar efficacy and  safety to HD metformin . This combination may be an alternative treatment option in patients who may have difficulty tolerating  metformin doses > 1000 mg/day . Funding Boehringer Ingelheim BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . 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 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 Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals . It has been demonstrated that metformin , an antihyperglycemic agent , decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus ( NIDDM ) adults . To evaluate the antiobesity effect of metformin , we conducted a r and omized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents ( body mass index [ BMI ] > 30 kg/m(2 ) ) . All subjects were placed on a low-calorie ( 1,500 kcal for women and 1,800 kcal for men ) meal plan . After an initial 1-week lead-in period , 12 subjects ( mean + /- SE for age and BMI , 15.6 + /- 0.4 and 41.2 + /- 1.8 , respectively ) received metformin ( 850 mg twice daily ) for 8 weeks , and 12 subjects ( mean + /- SE for age and BMI , 15.7 + /- 0.5 and 40.8 + /- 1.4 , respectively ) received placebo . Compared to the placebo group , the metformin group had greater weight loss ( 6.5 % + /- 0.8 % v 3.8 + /- 0.4 % , P < .01 ) , greater decrease in body fat ( P < .001 ) , greater increase in fat-free mass to body fat ratio ( P < .005 ) , and greater attenuation of area under the curve ( AUC ) insulin response to an oral glucose tolerance test ( P < .001 ) . This was associated with enhanced insulin sensitivity , as determined by the fasting plasma glucose : insulin , 2-hour glucose : insulin , and AUC glucose : AUC insulin ratios , in the metformin group compared to controls ( P < .01 ) . This corresponded to a significant reduction in plasma leptin ( P < .005 ) , cholesterol , triglycerides , and free fatty acid ( FFA ) levels ( P < .05 ) only in the metformin-treated subjects . Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone 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 BACKGROUND It has been hypothesized that metformin inhibits food intake , but in humans such effect needs to be demonstrated . Our study aims at investigating the effect of metformin administration on food intake in obese , non-diabetic , normotensive patients . METHODS Thirty patients underwent a double-blind , r and omized study .  Placebo ( P ; n = 15 ) and metformin ( M ; n = 15 ) were both given for 15 days , and food intake ( FI ) was recorded at baseline and in the last 4 days of each treatment period . RESULTS M administration allowed a stronger decline in body weight ( BW ) ( -2.8 + /- 1.6 vs. -0.3 + /- 0.4 kg P < 0.01 ) , body fat ( BF ) ( -1.4 + /- 1.2 vs. -0.3 + /- 1.1 kg P < 0.01 ) , plasma leptin concentration ( -5.2 + /- 8.9 vs. -1.8 + /- 10.4 ng mL-1 P < 0.05 ) and FI ( -642 + /- 491 vs.-70 + /- 1165 kJ per 24 h P < 0.01 ) than P. In M-treated subjects , changes in FI significantly correlated with those in BW ( r = 0.63 , P < 0.007 ) and BF ( r = 0.74 , P < 0.001 ) . Independently of sex and change in BF , the changes in FI and in fasting plasma leptin concentration ( r = 0.58 , P < 0.01 ) were still correlated . CONCLUSION Our study suggests that metformin administration is useful to inhibit FI and to lower BW and BF in obese non-diabetic patients Metformin improves insulin sensitivity , which is correlated to phospholipid fatty acid composition in obese type 2 diabetics . We aim ed at investigating the relationship between Metformin and fatty acids in obese insulin resistant non-diabetic individuals . A double-blind , placebo-controlled 20-week trial was performed in 21 BMI and age-matched insulin resistant non-diabetic individuals receiving either Metformin or placebo .  Insulin sensitivity together with metabolic parameters and fatty acids in serum phospholipids were measured at baseline and at 20 weeks . A significant decrease in body weight , BMI , percentage body fat , the sum of saturated fatty acids in serum phospholipids and increase in insulin sensitivity index were observed following the 20-week treatment . These changes did not differ significantly between the groups . Energy restriction rather than Metformin treatment appears to be responsible for the observed changes . The associations previously found in diabetics between insulin sensitivity and phospholipid fatty acids may not be mediated by Metformin OBJECTIVES To measure the effect of metformin on the body composition , insulin resistance and sensitivity in subjects with risk factors for type 2 diabetes mellitus ( type 2 DM ) . DESIGN Placebo-controlled clinical trial . MATERIAL AND METHODS Twenty-three subjects with risk factors for type 2 DM were r and omly assigned to receive 850 mg of metformin or a placebo twice a day for 2 months . Before and after the treatment , the body mass index and waist/hip ratio were calculated , the body composition was measured through bioelectric impedance and the fasting levels of blood glucose , insulin , triglycerides and cholesterol were measured . The level of insulin resistance was calculated by the homeostatic model and the level of sensitivity by the quantitative insulin sensitivity check index method . The Wilcoxon rank test was used . RESULTS Twenty-one subjects completed the study , 12 of the metformin group and nine of the placebo group . In the metformin group , there was a decrease in fat weight from 25.9 + /- 9.4 to 20.8 + /- 9.2 kg , p < 0.01 , an increase in lean weight from 57.05 + /- 13.6 to 61.9 + /- 16.5 kg , p < 0.01 , an increase in basal metabolism from 1735 + /- 413 to 1878 + /- 505 calories/day , p < 0.05 and an increase in body water , p < 0.05 . There was no significant decrease in insulin resistance . In the placebo group , the blood glucose increased from 84.7 + /- 13 to 96.7 + /- 16 mg/dl , p < 0.05 . There were no significant modifications in lipids . CONCLUSIONS The administration of metformin for 2 months improves the parameters of body composition and insulin dynamics in subjects with risk factors for type 2 DM 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
target: 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
background: 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 .