Determinants of weight loss maintenance: a systematic review. Comparative Effectiveness of Dipeptidylpeptidase-4 Inhibitors in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Systematic review of interventions in the management of overweight and obese children which include a dietary component Systematic review of interventions in the management of overweight and obese children which include a dietary component. Effects of workplace-based dietary and/or physical activity interventions for weight management targeting healthcare professionals: a systematic review of randomised controlled trials Long-Term Weight Loss With Metformin or Lifestyle Intervention in the Diabetes Prevention Program Outcomes Study [Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition]. The effect of comprehensive lifestyle intervention or metformin on obesity in young women. Metformin extended release treatment of adolescent obesity: a 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review Effectiveness of alternative listening devices to conventional hearing aids for adults with hearing loss: a systematic review protocol Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes. Effect of Metformin Added to Insulin on Glycemic Control Among Overweight/Obese Adolescents With Type 1 Diabetes: A Randomized Clinical Trial. Effect of metformin compared with hypocaloric diet on serum C-reactive protein level and insulin resistance in obese and overweight women with polycystic ovary syndrome. Physical activity in the treatment of the adulthood overweight and obesity: current evidence and research issues. Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study. Lifestyle intervention improves fitness independent of metformin in obese adolescents. [Indication of metformin in the management of hormonal dysfunction secondary to polycystic ovarian syndrome: prospective comparative study of 63 cases]. Risk Estimation Modeling and Feasibility Testing for a Mobile eHealth Intervention for Binge Drinking Among Young People: The D-ARIANNA (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults) Project. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Prefrontal cortex-mediated executive function as assessed by Stroop task performance associates with weight loss among overweight and obese adolescents and young adults Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review. A randomized, triple masked, placebo-controlled clinical trial for controlling childhood obesity Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Disparate effects of pharmacotherapy on plasma plasminogen activator inhibitor-1 levels in women with the polycystic ovary syndrome The effectiveness of methylphenidate in the management of Attention Deficit Hyperactivity Disorder (ADHD) in people with intellectual disabilities: A systematic review. A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: a pilot study. Effectiveness of interventions that assist caregivers to support people with dementia living in the community: a systematic review Efficacy and tolerability of rimonabant in overweight or obese patients with type 2 diabetes: a randomised controlled study Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin.
BACKGROUND Discerning the determinants of weight loss maintenance is important in the planning of future interventions and policies regarding overweight and obesity . We have therefore systematic ally synthesized recent literature on determinants of weight loss maintenance for individuals with overweight and obesity . METHODS With the use of the Preferred Reporting Items for Systematic Review s and Meta-Analyses statement , prospect i ve studies were identified from search es in PubMed and PsycINFO from 2006 to 2016 . We included articles investigating adults with overweight and obesity undergoing weight loss without surgery or medication .  Included articles were scored on their method ological quality , and a best- evidence synthesis was applied to summarize the results . RESULTS Our search result ed in 8,222 articles of which 67 articles were selected . In total , 124 determinants were identified of which 5 were demographic , 59 were behavioural , 51 were psychological/cognitive and 9 were social and physical environmental determinants . We found consistent evidence that demographic determinants were not predictive of weight loss maintenance . Behavioural and cognitive determinants that promote a reduction in energy intake , an increase in energy expenditure and monitoring of this balance are predictive determinants . CONCLUSION This review identifies key determinants in weight loss maintenance . However , more research regarding cognitive and environmental determinants of weight loss maintenance is needed to advance our knowledge on determinants of weight loss maintenance Objective To compare the safety and efficacy of the dipeptidylpeptidase-4 ( DPP-4 ) inhibitors in patients with type 2 diabetes and inadequate glycemic control . Design Systematic review of r and omized controlled trials ( RCTs ) , health economic evaluation studies , systematic review s , and meta-analyses , followed by primary Bayesian mixed treatment comparison meta-analyses ( MTCs ) , and secondary frequentist direct-comparison meta-analyses using a r and om-effects model . Outcomes were reported as weighted mean change from baseline , or odds ratio ( OR ) with 95 % credible interval . Data sources MEDLINE , MEDLINE In-Process , EMBASE , and BIOSIS via Dialog ProQuest ; Cochrane Central Register of Controlled Trials and Cochrane Data base of Systematic Review s via EBSCO ; four diabetes and two technical congress abstract s ; and health technology assessment organization websites . Eligibility criteria Patients with type 2 diabetes and inadequate glycemic control receiving any pharmacological anti-diabetic treatment . Data extraction and analysis Title/ abstract s were review ed for eligibility , followed by full-text review of publications remaining after first pass . A three-person team filtered articles and an independent review er checked a r and om selection ( 10 % ) of filtered articles . Data extraction and quality assessment of studies were also independently review ed . Five DPP-4 inhibitors ( alogliptin , linagliptin , saxagliptin , sitagliptin , and vildagliptin ) were compared via meta- analysis ( where data were available ) as monotherapy , dual therapy ( plus metformin , sulfonylurea , pioglitazone , or insulin ) , and triple therapy ( plus metformin/sulfonylurea ) . Results The review identified 6,601 articles ; 163 met inclusion criteria and 85 publications from 83 RCTs contained sufficient or appropriate data for analysis . MTCs demonstrated no differences between DPP-4 inhibitors in mean change from baseline in glycosylated hemoglobin ( HbA1c ) or body weight , or the proportions of patients achieving HbA1c < 7 % or experiencing a hypoglycemic event , apart from in patients on alogliptin plus metformin , who achieved HbA1c < 7 % more frequently than those treated with saxagliptin plus metformin [ OR 6.41 ( 95 % CI 3.15–11.98 ) versus 2.17 ( 95 % CI 1.56–2.95 ) ] . Conclusions This systematic review and MTC showed similar efficacy and safety for DPP-4 inhibitors as treatment for type 2 diabetes , either as monotherapy or combination therapy Background The prevalence of overweight and obesity in children and adolescents is increasing at an alarming rate around the world and prevention has become a key public health objective . Treatment and management of those already overweight and obese must be aligned with the best available evidence on effectiveness , if the risk of obesity‐related morbidity and mortality is yet be reduced . Diet plays a pivotal role in successful treatment of obesity but to date , there is limited evidence on which to base practice . Objectives To identify and present the best available evidence on the optimal dietetic treatment and management of children and adolescent who are overweight or obese . Search strategy Published English language literature was search ed using the electronic data bases CINAHL , MEDLINE , PRE‐ MEDLINE , DARE , COCHRANE , EMBASE , AUSTROM , Current Concepts and Dissertation Abstract s. The data bases were limited to English Language from 1975 until 2003 . Government reports from the UK , USA and Australian were also search ed and a h and search performed for the Journal of the Dietitians Association of Australia , International Journal of Obesity and the Journal of Human Nutrition and Dietetics and the bibliographies of retrieved articles . Selection criteria ( i ) Interventions that evaluated the effectiveness of nutrition or dietary interventions to treat or manage overweight and obesity ; ( ii ) Children aged less than 18 years ; and ( iii ) Participants were defined as overweight or obese by relative weight or a measure of body weight status , studies that reported body weight per se were excluded . Data collection and analysis An experienced professional librarian search ed the data bases , and two trained research assistants independently identified studies for retrieval and assessed each article for inclusion . The included studies were critically appraised for method ological quality by two people independently . Data were extracted from the appropriate articles and when a discrepancy arose , a third party would arbitrate . Main results There were 116 articles that met the inclusion criteria . While 49 articles described r and omised controlled trials , they arose from 37 separate studies . There were 67 non‐r and omised trials . Meta‐analyses were performed on eight studies that included both a dietary intervention component and an adequate control group and on four studies that had follow‐up data . There was a high degree of heterogeneity between studies and this made comparisons between studies problematic . Interventions that include diet therapy generally result in significant weight loss , at least in the short term . Many studies were poorly design ed and had no or only minimal follow up . The details of the dietary intervention were often inadequately described and dietary outcomes rarely reported , making repetition of the studies difficult . Review ers ' conclusions There is an urgent need for high quality studies investigating the optimal dietary approach to management of paediatric  overweight and obesity . These studies require adequate follow up to ascertain if weight loss can be sustained in the long term . Details of the dietary prescription , adherence to the dietary intervention and diet‐specific outcomes need to be reported in order to inform best practice Background The prevalence of overweight and obesity in children and adolescents is increasing at an alarming rate around the world and prevention has become a key public health objective . Treatment and management of those already overweight and obese must be aligned with the best available evidence on effectiveness , if the risk of obesity-related morbidity and mortality is yet be reduced . Diet plays a pivotal role in successful treatment of obesity but to date , there is limited evidence on which to base practice . Objectives To identify and present the best available evidence on the optimal dietetic treatment and management of children and adolescent who are overweight or obese . Search strategy Published English language literature was search ed using the electronic data bases CINAHL , MEDLINE , PRE- MEDLINE , DARE , COCHRANE , EMBASE , AUSTROM , Current Concepts and Dissertation Abstract s. The data bases were limited to English Language from 1975 until 2003 . Government reports from the UK , USA and Australian were also search ed and a h and search performed for the Journal of the Dietitians Association of Australia , International Journal of Obesity and the Journal of Human Nutrition and Dietetics and the bibliographies of retrieved articles . Selection criteria ( i ) Interventions that evaluated the effectiveness of nutrition or dietary interventions to treat or manage overweight and obesity ; ( ii ) Children aged less than 18 years ; and ( iii ) Participants were defined as overweight or obese by relative weight or a measure of body weight status , studies that reported body weight per se were excluded . Data collection and analysis An experienced professional librarian search ed the data bases , and two trained research assistants independently identified studies for retrieval and assessed each article for inclusion . The included studies were critically appraised for method ological quality by two people independently . Data were extracted from the appropriate articles and when a discrepancy arose , a third party would arbitrate . Main results There were 116 articles that met the inclusion criteria . While 49 articles described r and omised controlled trials , they arose from 37 separate studies . There were 67 non-r and omised trials . Meta-analyses were performed on eight studies that included both a dietary intervention component and an adequate control group and on four studies that had follow-up data . There was a high degree of heterogeneity between studies and this made comparisons between studies problematic . Interventions that include diet therapy generally result in significant weight loss , at least in the short term . Many studies were poorly design ed and had no or only minimal follow up . The details of the dietary intervention were often inadequately described and dietary outcomes rarely reported , making repetition of the studies difficult . Review ers ' conclusions There is an urgent need for high quality studies investigating the optimal dietary approach to management of paediatric overweight and obesity . These studies require adequate follow up to ascertain if weight loss can be sustained in the long term . Details of the dietary prescription , adherence to the dietary intervention and diet-specific outcomes need to be reported in order to inform best practice Background The prevalence of overweight and obesity is high amongst healthcare professionals and there is growing interest in delivering weight loss interventions in the workplace . We conducted a systematic review to ( i ) examine the effectiveness of workplace-based diet and /or physical activity interventions aim ed at healthcare professionals and to ( ii ) identify and describe key components of effective interventions . Seven electronic data bases were systematic ally search ed . Results Thirteen r and omised controlled trials met the inclusion criteria , of which seven had data available for meta- analysis . Where meta- analysis was possible , studies were grouped according to length of follow-up ( < 12 months and ≥12 months ) and behavioural target ( diet only , physical activity only or diet and physical activity ) , with outcome data pooled using a weighted r and om effects model . Nine studies reported statistically significant ( between-group ) differences . Four studies reported being informed by a behaviour change theory . Meta- analysis of all trials reporting weight data demonstrated healthcare professionals allocated to dietary and physical activity interventions lost significantly more body weight ( −3.95 Kg , [ 95 % CI −4.96 to- 2.95 Kg ] ) than controls up to 12 months follow up . Conclusions Workplace diet and /or physical activity interventions targeting healthcare professionals are limited in number and are heterogeneous . To improve the evidence base , we recommend additional evaluations of theory-based interventions and adequate reporting of intervention content 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 AIM The aim of this study was to evaluate the effects of diet alone , and in association with metformin in monotherapy or in cotreatment with myoinositol ( MYO ) on menstrual irregularities , hirsutism , body weight and composition in overweight/obese women with polycystic ovary syndrome ( PCOS ) . METHODS Twenty-seven PCOS overweight/obese patients were r and omly treated : nine with only diet ( D ) ; nine with diet and metformin 1000 mg/day continuously ( D+M ) ; nine with diet , metformin 500 mg/day and MYO 4 g/day plus 400 µg folic acid daily , continuously ( D+M+I ) . Menstrual cycle , Ferriman-Gallwey score , body mass index ( BMI ) , waist hip rate ( WHR ) , body composition by BIA 101 of AKERN SRL , were measured on basal condition and at 3 months . RESULTS Regularity of menstrual cycle was restored in a significantly number of patients of group D+M+I ( P<0.05 ) ; Ferriman score was significantly improved by weight loss ( P<0.05 ) . Body weight , BMI , waist and hip circumferences decreased significantly in all groups without WHR modification ; body weight loss significantly depended on adding metformin to diet . Fat mass ( FM ) kg and % was significantly reduced in groups D and D+M+I ; fat free mass ( FFM ) kg was slightly reduced by diet ( P<0.05 ) and correlated with Ferriman score . CONCLUSION Body weight loss  in obese PCOS patients improves symptoms and body composition ; weight loss was dependent on adding metformin to diet ; MYO was more effective in restoring regularity of menstrual cycle . Further investigation occurs to confirm metformin and MYO rule on body composition improvement , specially regarding FFM that is likewise FM correlated to cardiovascular risk 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 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 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 The prevalence of obesity and diabetes continues to rise in the US . Glucagon-like peptide-1 receptor agonist ( GLP-1RA ) is an effective treatment option for type 2 diabetes mellitus ( T2DM ) that promotes weight loss . Common and effective treatment options added to metformin therapy ( basal insulin , sulfonylureas , and pioglitazone ) contribute to weight gain , which makes the addition of GLP-1RAs advantageous . Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency . Until recently , there was a lack of data examining basal insulin combined with these agents . The main purpose of this article is to review the prospect i ve interventional data on the safety and efficacy of GLP-1RAs ( exenatide , liraglutide , albiglutide , lixisenatide ) combined with basal insulin therapy in nonpregnant adults with T2DM . Data bases search ed were PubMed , Cochrane Central Register of Controlled Trials and the Data base of Systematic Review s ( inception to January 2012 ) . Abstract s presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also review ed , as were reference lists of identified publications . A total of five studies met the criteria and were included in the review . Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes , such as additional lowering of A1c without major risk for hypoglycemia , lower basal insulin requirements , decreased postpr and ial glucose levels ( with or without fasting plasma glucose decreases ) , and weight loss , or at the very least , less weight gain . However , the gastrointestinal side effects and high cost of these agents may limit their use . This review demonstrates that adding a GLP-1RA to an existing basal insulin regimen is a reasonable treatment strategy in nonpregnant adult patients with T2DM Introduction Hearing loss is a major public health concern , affecting over 11 million people in the UK . While hearing aids are the most common clinical intervention for hearing loss , the majority of people that would benefit from using hearing aids do not take them up . Recent technological advances have led to a rapid increase of alternative listening devices to conventional hearing aids . These include hearing aids that can be customised using a smartphone , smartphone-based ‘ hearing aid ’ apps , personal sound amplification products and wireless hearing products . However , no systematic review has been published evaluating whether alternative listening devices are an effective management strategy for people with hearing loss . Methods and analysis The objective of this systematic review is to assess whether alternative listening devices are an effective intervention for adults with hearing loss . Methods are reported according to the Preferred Reporting Items for Systematic review s and Meta-analyses Protocol s ( PRISMA -P ) 2015 checklist . Retrospective or prospect i ve studies , r and omised controlled trials , non-r and omised controlled trials , and before-after comparison studies will be eligible for inclusion . We will include studies with adult participants ( ≥18 years ) with a mild or moderate hearing loss . The intervention should be an alternative listening device to a conventional hearing aid ( comparison ) . Studies will be restricted to outcomes associated with the consequences of hearing loss . We will search relevant data bases to identify published , completed but unpublished and ongoing trials . The overall quality of included evidence will be evaluated using the GRADE system , and meta- analysis performed if appropriate . Ethics and dissemination No ethical issues are foreseen . The findings will be reported at national and international conferences , primarily audiology , and ear , nose and throat , and in a peer- review ed journal using the PRISMA guidelines . Review registration number PROSPERO CRD4201502958 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 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 IMPORTANCE Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results . OBJECTIVE To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes . DESIGN , SETTING , AND PARTICIPANTS Multicenter ( 26 pediatric endocrinology clinics ) , double-blind , placebo-controlled r and omized clinical trial involving 140 adolescents aged 12.1 to 19.6 years ( mean [ SD ] 15.3 [ 1.7 ] years ) with mean type 1 diabetes duration 7.0 ( 3.3 ) years , mean body mass index ( BMI ) 94th ( 4 ) percentile , mean total daily insulin 1.1 ( 0.2 ) U/kg , and mean HbA1c 8.8 % ( 0.7 % ) . INTERVENTIONS R and omization to receive metformin ( n = 71 ) ( ≤2000 mg/d ) or placebo ( n = 69 ) . MAIN OUTCOMES AND MEASURES Primary outcome was change in HbA1c from baseline to 26 weeks adjusted for baseline HbA1c . Secondary outcomes included change in blinded continuous glucose monitor indices , total daily insulin , BMI , waist circumference , body composition , blood pressure , and lipids . RESULTS Between October 2013 and February 2014 , 140 participants were enrolled .  Baseline HbA1c was 8.8 % in each group . At 13-week follow-up , reduction in HbA1c was greater with metformin ( -0.2 % ) than placebo ( 0.1 % ; mean difference , -0.3 % [ 95 % CI , -0.6 % to 0.0 % ] ; P = .02 ) . However , this differential effect was not sustained at 26-week follow up when mean change in HbA1c from baseline was 0.2 % in each group ( mean difference , 0 % [ 95 % CI , -0.3 % to 0.3 % ] ; P = .92 ) . At 26-week follow-up , total daily insulin per kg of body weight was reduced by at least 25 % from baseline among 23 % ( 16 ) of participants in the metformin group vs 1 % ( 1 ) of participants in the placebo group ( mean difference , 21 % [ 95 % CI , 11 % to 32 % ] ; P = .003 ) , and 24 % ( 17 ) of participants in the metformin group and 7 % ( 5 ) of participants in the placebo group had a reduction in BMI z score of 10 % or greater from baseline to 26 weeks ( mean difference , 17 % [ 95 % CI , 5 % to 29 % ] ; P = .01 ) . Gastrointestinal adverse events were reported by more participants in the metformin group than in the placebo group ( mean difference , 36 % [ 95 % CI , 19 % to 51 % ] ; P < .001 ) . CONCLUSIONS AND RELEVANCE Among overweight adolescents with type 1 diabetes , the addition of metformin to insulin did not improve glycemic control after 6 months . Of multiple secondary end points , findings favored metformin only for insulin dose and measures of adiposity ; conversely , use of metformin result ed in an increased risk for gastrointestinal adverse events . These results do not support prescribing metformin to overweight adolescents with type 1 diabetes to improve glycemic control . TRIAL REGISTRATION clinical trials.org Identifier : NCT01881828 AIM The aim of the present study was to investigate the efficacy of Metformin compared with a hypocaloric diet on C-reactive protein ( CRP ) level and markers of insulin resistance in obese and overweight women with polycystic ovary syndrome ( PCOS ) . MATERIAL AND METHODS Forty women with body mass index ≥ 27 and PCOS were r and omly allocated to receive either Metformin or hypocaloric diet and were assessed before and after a treatment period of 12 weeks . High-sensitivity CRP ( hs-CRP ) and markers of insulin resistance ( IR ) , homeostasis model assessment -IR , quantitative insulin-sensitivity check index and fasting glucose to insulin ratio were evaluated in each patient . RESULTS A total of 10 subjects did not complete the trial ( three patients in the Metformin group and seven patients in the diet group ) and a total of 30 subjects completed the trial ( 17 subjects in the Metformin group and 13 subjects in the diet group ) . Serum concentration of hs-CRP significantly decreased in both the Metformin ( 5.29 ± 2.50 vs 3.81 ± 1.99 , P = 0.008 ) and diet groups ( 6.08 ± 2.14 vs 4.27 ± 1.60 , P = 0.004 ) . There were no significant differences in mean hs-CRP decrement between the two groups . Decrease in hs-CRP levels was significantly correlated with waist circumference in the diet group ( r = 0.8 , P < 0.001 ) . The effect of a hypocaloric diet with 5 - 10 % weight reduction on markers of insulin resistance ( homeostasis model assessment -IR , fasting glucose to insulin ratio , quantitative insulin-sensitivity check index ) was better than Metformin therapy ( P = 0.001 ) . CONCLUSIONS Although weight reduction has equal efficacy with Metformin in decreasing serum hs-CRP levels , it was significantly more effective in improving insulin resistance in obese and overweight PCOS women PURPOSE The purpose of this paper is to review the evidence on the role of physical activity in the treatment of adult overweight and obesity . Three specific questions are addressed : ( 1 ) Does exercise alone produce weight loss ? ( 2 ) Does exercise in combination with diet produce greater weight loss than diet only ? and ( 3 ) Does exercise in combination with diet produce better maintenance of weight loss than diet alone ? METHODS The literature initially identified by the Expert Panel on Clinical Guidelines for the Treatment of Obesity , three key meta analyses , and additional literature search es were used to identify r and omized trials related to the three aforementioned topics . These articles were review ed and tabulated . RESULTS Six of 10 r and omized studies found significantly greater weight loss in exercise alone versus no treatment controls . The magnitude of the effect averaged 1 - 2 kg . Only 2 of 13 studies found significant differences in initial weight loss for diet plus exercise versus diet only , although almost all studies pointed in this direction . Six studies were identified with maintenance periods of at least 1 yr . In two of the six there were significant long term differences favoring diet plus exercise , but in every study considered the direction of the difference favored diet plus exercise . Other strong evidence showing benefits of exercise for long-term weight loss comes from correlational analyses which consistently find that those individuals who report the greatest exercise have the best maintenance of weight loss . CONCLUSIONS R and omized trials consistently show benefits of exercise for weight loss , but the effects are often modest . This may result from small sample sizes , short study duration , and poor adherence to the exercise prescriptions . To better define the doses and types of exercise that will promote long-term weight loss , it is necessary to develop better ways to measure exercise and promote adherence to exercise 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 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 BACKGROUND Polycystic ovarian syndrome ( PCOS ) is the most common hormonal dysfunction in women . It 's a cause of female infertility by oligoanovulation , clinical and biochemical hyper and rogenism and polycystic ovaries . Weight loss , firstly proposed in overweight or obese patient suffering from PCOS , aims to reduce hyperinsulinism and hyper and rogenism . Recently , Metformin , an insulin sensitizer , has been proposed as an alternative first line treatment for polycystic ovarian syndrome by improving hyperinsulinemia and hyper and rogenism in these women . AIM The aim of our study , and through a literature review , is to demonstrate if Metformin should be used as a first-line drug for infertile women with this syndrome or as an adjunction to Clomifene Citrate , the longest established treatment already used in this syndrome . METHODS A prospect i ve comparative study including 63 patients with PCOS has been done during 2 years . Women were r and omly allocated to clomifene + Metformin ( Metformin group , Metformin took during 8 weeks , 850 mg twice a day , plus Clomifene 100 mg per day during five days ) or Clomifene only ( 100 mg per day during five days ) . All patients underwent a two- month 's diet . RESULTS The middle age was about 30.63 years and the body mass index ( BMI ) was about 29.88 kg/ m(2 ) . We noticed a 6.2 % weight loss in both groups ( a non significant difference in p=0.04 ) . The median of infertility period was about 2.49 years . The ovulation rate in the Metformin group was 53.12 % ( significant difference for inducing ovulation p=0.02 ) and 32.25 % in Clomifene group ( non-significant difference 0.07 ) . There was also a significant difference for ongoing pregnancies ( p=0.04 ) . In fact , 11 on 32 patients ( 34 % ) achieved a full-term pregnancy in Metformin group versus only 4 ones on 31 patients ( 12.9 % ) in Clomifene group . CONCLUSION Our conclusion is that Metformin is an effective addition to Clomifene Citrate in term of reestablishment of ovulation and full-term pregnancies achievement , excluding ART cycles BACKGROUND Binge drinking is common among young people but often relevant risk factors are not recognized . eHealth apps , attractive for young people , may be useful to enhance awareness of this problem . We aim ed at developing a current risk estimation model for binge drinking , incorporated into an eHealth app -- D-ARIANNA ( Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults)--for young people . METHODS A longitudinal approach with phase 1 ( risk estimation ) , phase 2 ( design ) , and phase 3 ( feasibility ) was followed . Risk/protective factors identified from the literature were used to develop a current risk estimation model for binge drinking . Relevant odds ratios were subsequently pooled through meta-analytic techniques with a r and om-effects model , deriving weighted estimates to be introduced in a final model . A set of questions , matching identified risk factors , were nested in a question naire and assessed for wording , content , and acceptability in focus groups involving 110 adolescents and young adults . RESULTS Ten risk factors ( 5 modifiable ) and 2 protective factors showed significant associations with binge drinking and were included in the model . Their weighted coefficients ranged between -0.71 ( school proficiency ) and 1.90 ( cannabis use ) . The model , nested in an eHealth app question naire , provides in percent an overall current risk score , accompanied by appropriate images . Factors that mostly contribute are shown in summary messages . Minor changes have been realized after focus groups review . Most of the subjects ( 74 % ) regarded the eHealth app as helpful to assess binge drinking risk . CONCLUSIONS We could produce an evidence -based eHealth app for young people , evaluating current risk for binge drinking . Its effectiveness will be tested in a large trial 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 HighlightsWe present associations of executive function with weight loss among overweight and obese adolescents and young adults . We performed a prospect i ve weight loss study with combination of exercise training and food restriction . Greater executive function correlated with better weight loss . ABSTRACT People with cognitive deficits or executive dysfunction are often overweight or obese . Several human neuroimaging studies have found that executive function ( EF ) predicts food intake and weight gain ; however , fewer studies have investigated the relationship between EF and weight loss . The Stroop task is a classic measure of EF that is used in many neuroimaging studies . In the present work , functional near infrared spectroscopy ( fNIRS ) data were collected during performance of the Stroop task from a sample of overweight or obese adolescents and young adults ( n = 31 ) who participated in a summer fitness and weight loss camp . We assessed the Stroop effect by interference in the reaction time ( RT ) to visual challenges , and by alterations in levels of oxygenated hemoglobin , as detected by fNIRS . In line with previous studies , we found that the Stroop effect was successfully induced by different visual task conditions among obese/overweight individuals . Moreover , our results reveal that better Stroop task performance is correlated with greater weight loss over a4‐weekfitness intervention . Indeed , behavioral data demonstrated that reduced RT interference predicted a greater percentage of weight loss . Moreover , overweight/obese individuals with a greater hemodynamic response in the left ventrolateral and bilateral dorsolateral prefrontal cortex due to the Stroop effect lost more weight during the short‐term fitness intervention than participants with lower levels of activation of these neural regions . Overall , our results support a role for prefrontal cortex‐mediated EF in influencing food intake and weight loss outcomes in a population of a previously unstudied age OBJECTIVES The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . INCLUSION CRITERIA Types of participants Adult caregivers who provide support for people with dementia living in the community ( non-institutional care).Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team - for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta-analyses , systematic review s , r and omised control trials , quasi-experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . SEARCH STRATEGY The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . ASSESSMENT OF QUALITY Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . DATA COLLECTION AND ANALYSIS St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta- analysis . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . RESULTS A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty-five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta- analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta- analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta- analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi-square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well-being , self-efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta- analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . EFFECTIVENESS OF INTERVENTION TYPE Four categories of intervention were included in the review - psycho-educational , support , multi-component and other . Psycho-educational Thirteen studies used  psycho-educational interventions  , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta- analysis . No significant impact of psycho-educational interventions was found for the outcome categories of subjective well-being , self-efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta- analysis and demonstrated a small but significant improvement on caregiver burden . Multi-component Twelve of the studies report multi-component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self-efficacy , depression , subjective well-being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta- analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits . Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . EFFECTIVENESS OF INTERVENTIONS USING SPECIFIC OUTCOME CATEGORIES In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on caregiver depression was available for meta- analysis from eight studies . This indicated that multi-component and psycho-educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta- analysis and findings indicated that there were no significant effects of any of interventions . No meta- analysis was possible for the outcome categories of health , self-efficacy or subjective well-being . IMPLICATION S FOR PRACTICE From this review there is evidence to support the use of well- design ed psycho-educational or multi-component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Factors which do not appear to have benefit in interventions are those which 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 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 OBJECTIVE : Polycystic ovary syndrome ( PCOS ) is characterized by obesity and insulin resistance ( IR ) , which result in elevated plasminogen activator inhibitor-1 ( PAI-1 ) levels . We aim ed to assess the changes in PAI-1 levels in PCOS during treatment with metformin and during weight loss . DESIGN : Twenty-three normal weight women with PCOS were given metformin 850 mg bid for 6 months . Fifty overweight/obese women with PCOS were prescribed an energy-restricted diet , were instructed to exercise and were r and omized to orlistat 120 mg tid or sibutramine 10 mg qd for 6 months . RESULTS : In normal weight women , treatment with metformin reduced the body mass index ( BMI ) and circulating and rogens , improved markers of IR and lowered PAI-1 levels . In overweight/obese women , sibutramine and orlistat yielded comparable reductions in BMI and markers of IR . In contrast , the effects on the free and rogen index ( FAI ) differed ( p=0.027 ) : sibutramine reduced the FAI ( p=0.005 ) , whereas orlistat had no effect . The effects of sibutramine and orlistat on PAI-1 levels also differed ( p=0.042 ) : sibutramine  reduced PAI-1 levels ( p<0.001 ) , whereas orlistat had no effect . CONCLUSIONS : Metformin and sibutramine , but not orlistat , reduce PAI-1 levels in PCOS . The reduction in circulating and rogens during metformin and sibutramine treatment might be implicated in this decline BACKGROUND The effectiveness of psychostimulants , primarily methylpheni date ( MPH ) , in the treatment of Attention Deficit Hyperactivity Disorder ( ADHD ) in the general population of typically growing children and adolescents is well established through many R and omised Controlled Trials ( RCTs ) . AIMS AND METHODS We carried out a systematic review of all the RCTs in people with intellectual disabilities ( ID ) that assessed effectiveness of MPH on the core ADHD symptoms . OUTCOMES AND RESULTS We included 15 papers from 13 studies that were all on children and adolescents with ID ( 315 participants were on MPH and placebo respectively ) , 12 of which used a cross over design , and one used a parallel design . On average around 40 - 50 % responded to MPH in the ID group whereas around 70 - 80 % response rate is reported among the non-ID children . Because of the heterogeneity of the outcome data it was not possible to carry out a meta- analysis . Significant adverse events included sleep difficulties and poor appetite along with weight loss and also irritability , social withdrawal and increased motor activities including tic . CONCLUSIONS AND IMPLEMENTATION On the basis of the poor quality evidence that is available , it seems that MPH may be effective in some but not all children and adolescents with ID and ADHD OBJECTIVE To obtain data from a pilot r and omized trial on the effect of metformin therapy and lifestyle modification on ovulation and and rogen concentrations in women with polycystic ovary syndrome ( PCOS ) . DESIGN Prospect i ve , r and omized , placebo-controlled pilot trial . SETTING Academic medical center . PATIENT(S ) Thirty-eight overweight or obese women with PCOS . INTERVENTION(S ) All subjects were r and omized to one of four 48-week interventions : metformin 850 mg two times per day , lifestyle modification plus metformin 850 mg two times per day , lifestyle modification plus placebo , or placebo alone . MAIN OUTCOME MEASURE(S ) Recruitment , dropout , and compliance with a long-term lifestyle intervention in PCOS ; preliminary estimates of treatment effect on ovulation , as measured by weekly urinary pregnanediol glucuronide , and on total T and free and rogen index . RESULT ( S ) It was necessary to screen seven women to have one subject r and omized . The dropout rate was 39 % , with the majority of dropouts occurring within the first 24 weeks . Mean body mass index was > 39 mg/kg(2 ) . Modest weight reduction was found in all treatment groups , with the most significant reduction occurring with the combination of metformin and lifestyle intervention .  Significant and rogen reduction occurred in the combination group only . Ovulation rates did not differ significantly between groups . However , when data were analyzed by presence or absence of weight reduction in subjects , independent of treatment group , the estimated odds ratio for weight loss was 9.0 ( 95 % confidence interval 1.2 - 64.7 ) with respect to regular ovulation . If weight loss occurred during metformin therapy , the odds ratio for regular ovulation was 16.2 ( 95 % confidence interval 4.4 - 60.2 ) . CONCLUSION ( S ) Key method ologic issues for a large-scale , r and omized trial of lifestyle intervention in PCOS include minimizing early dropout from the lifestyle intervention and including a range of body mass index that is not skewed toward severe obesity . Weight reduction might play the most significant role in restoration of ovulation in obese women with PCOS Objectives The objective of this review was to assess the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Inclusion criteria Types of participants Adult caregivers who provide support for people with dementia living in the community ( non‐institutional care ) . Types of interventions Interventions design ed to support caregivers in their role such as skills training , education to assist in caring for a person living with dementia and support groups/programs . Interventions of formal approaches to care design ed to support caregivers in their role , care planning , case management and specially design ated members of the healthcare team ‐ for example dementia nurse specialist or volunteers trained in caring for someone with dementia . Types of studies This review considered any meta‐analyses , systematic review s , r and omised control trials , quasi‐experimental studies , cohort studies , case control studies and observational studies without control groups that addressed the effectiveness of interventions that assist caregivers to provide support for people living with dementia in the community . Search strategy The search sought to identify published studies from 2000 to 2005 through the use of electronic data bases . Only studies in English were considered for inclusion . The initial search was conducted of the data bases , CINAHL , MEDLINE and PsychINFO using search strategies adapted from the Cochrane Dementia and Cognitive Improvement Group . A second more extensive search was then conducted using the appropriate Medical Subject Headings ( MeSH ) and keywords for other available data bases . Finally , h and search ing of reference lists of articles retrieved and of core dementia , geriatric and psycho geriatric journals was undertaken . Assessment of quality Method ological quality of each of the articles was assessed by two independent review ers using appraisal checklist developed by the Joanna Briggs Institute and based on the work of the Cochrane Collaboration and Centre for Review s and Dissemination . Data collection and analysis St and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each included study reported in the meta‐ analysis . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software from the Cochrane Collaboration . Heterogeneity between combined studies was tested using st and ard chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . Results A comprehensive search of relevant data bases , h and search ing and cross referencing found 685 articles that were assessed for relevance to the review . Eighty‐five papers appeared to meet the inclusion criteria based on title and abstract , and the full paper was retrieved . Of the 85 full papers review ed , 40 were accepted for inclusion , three were systematic review s , three were meta‐ analysis , and the remaining 34 were r and omised controlled trials . For the r and omised controlled trials that were able to be included in a meta‐ analysis , st and ardised mean differences or weighted mean differences and their 95 % confidence intervals were calculated for each . Results from comparable groups of studies were pooled in statistical meta‐ analysis using Review Manager Software and heterogeneity between combined studies was assessed by using the chi‐square test . Where statistical pooling was not appropriate or possible , the findings are summarised in narrative form . The results are discussed in two main sections . Firstly it was possible to assess the effectiveness of different types of caregiver interventions on the outcome categories of depression , health , subjective well‐being , self‐efficacy and burden . Secondly , results are reported by main outcome category . For each of these sections , meta‐ analysis was conducted where it was possible ; otherwise , a narrative summary describes the findings . Effectiveness of intervention type Four categories of intervention were included in the review ‐ psycho‐educational , support , multi‐component and other . Psycho‐educational Thirteen studies used  psycho‐educational interventions , and all but one showed positive results across a range of outcomes . Eight studies were entered in a meta‐ analysis . No significant impact of psycho‐educational interventions was found for the outcome categories of subjective well‐being , self‐efficacy or health . However , small but significant results were found for the categories of depression and burden . Support Seven studies discussed support only interventions and two of these showed significant results . These two studies were suitable for meta‐ analysis and demonstrated a small but significant improvement on caregiver burden . Multi‐component Twelve of the studies report multi‐component interventions and 10 of these report significant outcomes across a broad range of outcome measures including self‐efficacy , depression , subjective well‐being and burden . Unfortunately because of the heterogeneity of study design s and outcome measures , no meta‐ analysis was possible . Other interventions Other interventions included the use of exercise or nutrition which result ed in improvements in psychological distress and health benefits .  Case management and a computer aided support intervention provided mixed results . One cognitive behavioural therapy study reported a reduction in anxiety and positive impacts on patient behaviour . Effectiveness of interventions using specific outcome categories In addition to analysis by type of intervention it was possible to analyse results based on some outcome categories that were used across the studies . In particular the impact of interventions on  caregiver depression was available for meta‐ analysis from eight studies . This indicated that multi‐component and psycho‐educational interventions showed a small but significant positive effect on caregiver depression . Five studies using the outcome category of caregiver burden  were entered into a meta‐ analysis and findings indicated that there were no significant effects of any of interventions . No meta‐ analysis was possible for the outcome categories of health , self‐efficacy or subjective well‐being . Implication s for practice From this review there is evidence to support the use of well‐ design ed psycho‐educational or multi‐component interventions for caregivers of people with dementia who live in the community . Factors that appear to positively contribute to effective interventions are those which : Provide opportunities within the intervention for the person with dementia as well as the caregiver to be involved Encourage active participation in educational interventions for caregivers Offer individualised programs rather than group sessions Provide information on an ongoing basis , with specific information about services and coaching regarding their new role Target the care recipient particularly by reduction in behaviours Factors which do not appear to have benefit in interventions are those which : Simply refer caregivers to support groups Only provide self help material s Only offer peer BACKGROUND Rimonabant , a selective cannabinoid type 1 receptor blocker , reduces bodyweight and improves cardiovascular and metabolic risk factors in non-diabetic overweight or obese patients . The aim of the RIO-Diabetes trial was to assess the efficacy and safety of rimonabant in overweight or obese patients with type 2 diabetes that was inadequately controlled by metformin or sulphonylureas . METHODS 1047 overweight or obese type 2 diabetes patients ( body-mass index 27 - 40 kg/m2 ) with a haemoglobin A1c ( HbA1c ) concentration of 6.5 - 10.0 % ( mean 7.3 % [ SD 0.9 ] at baseline ) already on metformin or sulphonylurea monotherapy  were given a mild hypocaloric diet and advice for increased physical activity , and r and omly assigned placebo ( n=348 ) , 5 mg/day rimonabant ( 360 ) or 20 mg/day rimonabant ( 339 ) for 1 year . Two individuals in the 5 mg/day group did not receive double-blind treatment and were thus not included in the final analysis . The primary endpoint was weight change from baseline after 1 year of treatment . Analyses were done on an intention-to-treat basis . This trial is registered at Clinical Trials.gov , number NCT00029848 . FINDINGS 692 patients completed the 1 year follow-up ; numbers in each group after 1 year were much the same . Weight loss was significantly greater after 1 year in both rimonabant groups than in the placebo group ( placebo : -1.4 kg [ SD 3.6 ] ; 5 mg/day : -2.3 kg [ 4.2 ] , p=0.01 vs placebo ; 20 mg/day : -5.3 kg [ 5.2 ] , p<0.0001 vs placebo ) . Rimonabant was generally well tolerated . The incidence of adverse events that led to discontinuation was slightly greater in the 20 mg/day rimonabant group , mainly due to depressed mood disorders , nausea , and dizziness . INTERPRETATION These data indicate that 20 mg/day rimonabant , in combination with diet and exercise , can produce a clinical ly meaningful reduction in bodyweight and improve HbA1c and a number of cardiovascular and metabolic risk factors in overweight or obese patients with type 2 diabetes inadequately controlled by metformin or sulphonylureas OBJECTIVE The purpose of this study was to assess the effect of orlistat , a gastrointestinal lipase inhibitor , on body weight , glycemic control , and cardiovascular risk factors in metformin-treated type 2 diabetic patients . RESEARCH DESIGN AND METHODS A 1-year multicenter , r and omized , double-blind , placebo-controlled trial of 120 mg  orlistat t.i.d . ( n = 249 ) or placebo ( n = 254 )  combined with a reduced-calorie diet was conducted in overweight and obese patients with suboptimal control of type 2 diabetes . RESULTS After 1 year of treatment , mean ( + /-SE ) weight loss was greater in the orlistat than in the placebo group ( -4.6 + /- 0.3 % vs. -1.7 + /- 0.3 % of baseline wt , P < 0.001 ) . Orlistat treatment caused a greater improvement in glycemic control than placebo , as evidence d by a greater reduction in serum HbA(1c ) , adjusted for changes in metformin and sulfonylurea therapy ( -0.90 + /- 0.08 vs. -0.61 + /- 0.08 , P = 0.014 ) ; a greater proportion of patients achieving decreases in HbA(1c ) of > or = 0.5 and > or = 1.0 % ( both P < 0.01 ) ; and a greater reduction in fasting serum glucose ( -2.0 + /- 0.2 vs. -0.7 + /- 0.2 mmol/l , P = 0.001 ) . Compared with the placebo group , patients treated with orlistat also had greater decreases in total cholesterol , LDL cholesterol , and systolic blood pressure ( all P < 0.05 ) . Although more subjects treated with orlistat experienced gastrointestinal side effects than placebo ( 83 vs. 62 % , P < 0.05 ) , more subjects in the placebo group withdrew prematurely from the study than in the orlistat group ( 44 vs. 35 % , P < 0.05 ) . CONCLUSIONS Orlistat is a useful adjunctive treatment for producing weight loss and improving glycemic control , serum lipid levels , and blood pressure in obese patients with type 2 diabetes who are being treated with metformin
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 .