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The Cochrane Database of Systematic... Mar 2019Child and adolescent obesity is increasingly prevalent, and can be associated with significant short- and long-term health consequences. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Child and adolescent obesity is increasingly prevalent, and can be associated with significant short- and long-term health consequences.
OBJECTIVES
To assess the efficacy of lifestyle, drug and surgical interventions for treating obesity in childhood.
SEARCH METHODS
We searched CENTRAL on The Cochrane Library Issue 2 2008, MEDLINE, EMBASE, CINAHL, PsycINFO, ISI Web of Science, DARE and NHS EED. Searches were undertaken from 1985 to May 2008. References were checked. No language restrictions were applied.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of lifestyle (i.e. dietary, physical activity and/or behavioural therapy), drug and surgical interventions for treating obesity in children (mean age under 18 years) with or without the support of family members, with a minimum of six months follow up (three months for actual drug therapy). Interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity were excluded.
DATA COLLECTION AND ANALYSIS
Two reviewers independently assessed trial quality and extracted data following the Cochrane Handbook. Where necessary authors were contacted for additional information.
MAIN RESULTS
We included 64 RCTs (5230 participants). Lifestyle interventions focused on physical activity and sedentary behaviour in 12 studies, diet in 6 studies, and 36 concentrated on behaviorally orientated treatment programs. Three types of drug interventions (metformin, orlistat and sibutramine) were found in 10 studies. No surgical intervention was eligible for inclusion. The studies included varied greatly in intervention design, outcome measurements and methodological quality.Meta-analyses indicated a reduction in overweight at 6 and 12 months follow up in: i) lifestyle interventions involving children; and ii) lifestyle interventions in adolescents with or without the addition of orlistat or sibutramine. A range of adverse effects was noted in drug RCTs.
AUTHORS' CONCLUSIONS
While there is limited quality data to recommend one treatment program to be favoured over another, this review shows that combined behavioural lifestyle interventions compared to standard care or self-help can produce a significant and clinically meaningful reduction in overweight in children and adolescents. In obese adolescents, consideration should be given to the use of either orlistat or sibutramine, as an adjunct to lifestyle interventions, although this approach needs to be carefully weighed up against the potential for adverse effects. Furthermore, high quality research that considers psychosocial determinants for behaviour change, strategies to improve clinician-family interaction, and cost-effective programs for primary and community care is required.
Topics: Anti-Obesity Agents; Child; Diet, Reducing; Humans; Life Style; Motor Activity; Pediatric Obesity; Randomized Controlled Trials as Topic
PubMed: 30843601
DOI: 10.1002/14651858.CD001872.pub3 -
Health Technology Assessment... Nov 2018Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m] have an increased risk of comorbidities and psychological, social and economic consequences. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adults with severe obesity [body mass index (BMI) of ≥ 35 kg/m] have an increased risk of comorbidities and psychological, social and economic consequences.
OBJECTIVES
Systematically review bariatric surgery, weight-management programmes (WMPs) and orlistat pharmacotherapy for adults with severe obesity, and evaluate the feasibility, acceptability, clinical effectiveness and cost-effectiveness of treatment.
DATA SOURCES
Electronic databases including MEDLINE, EMBASE, PsycINFO, the Cochrane Central Register of Controlled Trials and the NHS Economic Evaluation Database were searched (last searched in May 2017).
REVIEW METHODS
Four systematic reviews evaluated clinical effectiveness, cost-effectiveness and qualitative evidence for adults with a BMI of ≥ 35 kg/m. Data from meta-analyses populated a microsimulation model predicting costs, outcomes and cost-effectiveness of Roux-en-Y gastric bypass (RYGB) surgery and the most effective lifestyle WMPs over a 30-year time horizon from a NHS perspective, compared with current UK population obesity trends. Interventions were cost-effective if the additional cost of achieving a quality-adjusted life-year is < £20,000-30,000.
RESULTS
A total of 131 randomised controlled trials (RCTs), 26 UK studies, 33 qualitative studies and 46 cost-effectiveness studies were included. From RCTs, RYGB produced the greatest long-term weight change [-20.23 kg, 95% confidence interval (CI) -23.75 to -16.71 kg, at 60 months]. WMPs with very low-calorie diets (VLCDs) produced the greatest weight loss at 12 months compared with no WMPs. Adding a VLCD to a WMP gave an additional mean weight change of -4.41 kg (95% CI -5.93 to -2.88 kg) at 12 months. The intensive Look AHEAD WMP produced mean long-term weight loss of 6% in people with type 2 diabetes mellitus (at a median of 9.6 years). The microsimulation model found that WMPs were generally cost-effective compared with population obesity trends. Long-term WMP weight regain was very uncertain, apart from Look AHEAD. The addition of a VLCD to a WMP was not cost-effective compared with a WMP alone. RYGB was cost-effective compared with no surgery and WMPs, but the model did not replicate long-term cost savings found in previous studies. Qualitative data suggested that participants could be attracted to take part in WMPs through endorsement by their health-care provider or through perceiving innovative activities, with WMPs being delivered to groups. Features improving long-term weight loss included having group support, additional behavioural support, a physical activity programme to attend, a prescribed calorie diet or a calorie deficit.
LIMITATIONS
Reviewed studies often lacked generalisability to UK settings in terms of participants and resources for implementation, and usually lacked long-term follow-up (particularly for complications for surgery), leading to unrealistic weight regain assumptions. The views of potential and actual users of services were rarely reported to contribute to service design. This study may have failed to identify unpublished UK evaluations. Dual, blinded numerical data extraction was not undertaken.
CONCLUSIONS
Roux-en-Y gastric bypass was costly to deliver, but it was the most cost-effective intervention. Adding a VLCD to a WMP was not cost-effective compared with a WMP alone. Most WMPs were cost-effective compared with current population obesity trends.
FUTURE WORK
Improved reporting of WMPs is needed to allow replication, translation and further research. Qualitative research is needed with adults who are potential users of, or who fail to engage with or drop out from, WMPs. RCTs and economic evaluations in UK settings (e.g. Tier 3, commercial programmes or primary care) should evaluate VLCDs with long-term follow-up (≥ 5 years). Decision models should incorporate relevant costs, disease states and evidence-based weight regain assumptions.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016040190.
FUNDING
The National Institute for Health Research Health Technology Assessment programme. The Health Services Research Unit and Health Economics Research Unit are core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorate.
Topics: Anti-Obesity Agents; Bariatric Surgery; Behavior Therapy; Cost-Benefit Analysis; Exercise; Humans; Life Style; National Health Programs; Obesity, Morbid; Orlistat; Technology Assessment, Biomedical; Treatment Outcome; United Kingdom
PubMed: 30511918
DOI: 10.3310/hta22680 -
Journal of Obstetrics and Gynaecology... Oct 2018Polycystic ovarian syndrome (PCOS), a commonly prevalent endocrinopathy among reproductive age group women, is most often associated with obesity. Increased insulin... (Review)
Review
BACKGROUND
Polycystic ovarian syndrome (PCOS), a commonly prevalent endocrinopathy among reproductive age group women, is most often associated with obesity. Increased insulin resistance appears to be the central pathophysiologic mechanism responsible for various complications of PCOS. This makes 'weight loss' as the first-line treatment approach in PCOS. So various trials have tried to compare metformin (an insulin-sensitizing agent) and orlistat (an anti-obesity drug) aiming to achieve weight loss and hence higher ovulation rate for the group of obese PCOS patients. Keeping an eye on all these background facts, we designed this systematic review and metaanalysis to compare the effects of metformin and orlistat on various aspects of PCOS and to pick the better among the two drugs.
MATERIALS AND METHODS
This is a systemic review of randomized control trials that studied the effectiveness of orlistat versus metformin in terms of improvement in ovulation rate, weight loss, lipid profile, etc. Systematic literature search over the period January 2000-December 2016 was performed in the following electronic databases: Medline, embase, google scholar, pubmed and The Cochrane Library and only randomized controlled clinical trials were included in our study. All authors carefully went through all sources of information independently.
RESULTS
According to this study, weight loss, testosterone level after 4 weeks of treatment, total serum cholesterol and triglyceride level showed significant fall in orlistat-treated group.
CONCLUSION
Our review shows that orlistat is a more effective drug than metformin and should be the preferred drug in obese PCOS in combination with weight loss.
PubMed: 30224835
DOI: 10.1007/s13224-018-1140-6 -
Obesity Reviews : An Official Journal... Sep 2018Obesity is an independent risk factor for the development of heart failure, and the two commonly co-exist. The European Society of Cardiology does not provide guidance...
OBJECTIVE
Obesity is an independent risk factor for the development of heart failure, and the two commonly co-exist. The European Society of Cardiology does not provide guidance regarding weight loss strategies in heart failure. The aim of this study was to systematically review the evidence for outcomes following intentional weight loss in patients with heart failure and obesity.
METHOD
A systematic review of English articles was undertaken using databases PubMed, Embase and CENTRAL. Randomized controlled trials and observational studies reporting outcomes following intentional weight loss by lifestyle, surgical or pharmacotherapy intervention in patients with obesity and heart failure were included.
RESULTS
Four randomized controlled trials and seven observational studies were identified. Two randomized controlled trials used diet and exercise as an intervention, one used diet alone and one used a pharmacological intervention (orlistat). All but one reported significant weight loss. Two reported improvement in exercise capacity and quality of life. One reported improvement in New York Heart Association functional class in heart failure with preserved ejection fraction. The observational studies, five of which reported on outcomes following bariatric surgery, despite being small, heterogeneous and high risk of bias, suggested a trend in improvement of left ventricular function, quality of life and exercise capacity following weight loss.
CONCLUSION
Weight loss is achievable with lifestyle intervention in those with heart failure and obesity and may result in improvements in New York Heart Association classification, quality of life and exercise capacity.
Topics: Anti-Obesity Agents; Body Mass Index; Diet, Reducing; Exercise; Heart Failure; Humans; Obesity; Orlistat; Quality of Life; Weight Loss
PubMed: 30051959
DOI: 10.1111/obr.12707 -
Biomedical Reports Jul 2018In the present meta-analysis, the efficacy and safety of orlistat in the treatment of non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) were...
In the present meta-analysis, the efficacy and safety of orlistat in the treatment of non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH) were evaluated. PubMed, Embase, the Cochrane Library, Web of Science, and Wan Fang data were searched for controlled trials of orlistat in patients with NAFLD or NASH, published before August 2017. Three randomized controlled trials and four single-arm trials were included. The involved participants with NAFLD or NASH (330 patients) were analyzed for clinical outcomes including alteration in hepatic histological variables and biomarkers of liver function. Improvements were observed in levels of alanine aminotransferase [standard mean difference (SMD)=-1.41; P=0.01], aspartate aminotransferase (SMD=-2.06; P=0.0005), γ-glutamyl transpeptidase (SMD=-1.91; P=0.05), glucose [mean difference (MD)=-0.51; P=0.01], triglycerides (MD=-0.93; P=0.01), homeostasis model assessment of insulin resistance index (MD=-1.05; P=0.04) and body mass index (MD=-1.97; P=0.02), but not in liver fibrosis score (SMD=-0.14; P=0.71). On sub-analyses of the different patient groups, no significant differences were observed in patients with NASH. Taken together, these findings demonstrate that orlistat could serve as a therapeutic drug to improve biochemical indicators of liver damage, but not as first-choice drug for the management of NAFLD or NASH; thus suggesting a novel palliative drug only for the treatment of NAFLD.
PubMed: 29930810
DOI: 10.3892/br.2018.1100 -
Gastroenterology Apr 2018We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
We performed a systematic review and network meta-analysis to evaluate the overall and comparative effects of weight-loss medications approved by the Food and Drug Administration for long-term use on cardiometabolic risk profiles of obese adults.
METHODS
We performed a systematic literature review through February 28, 2017 to identify randomized clinical trials of the effects of Food and Drug Administration-approved weight-loss medications (ie, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide) administered to obese adults for 1 year or more, compared with placebo or another active agent. Outcomes of interest included changes in blood glucose (fasting blood glucose [FBG] and hemoglobin A1c), cholesterol profile (low-density lipoprotein and high-density lipoproteins), blood pressure (BP; systolic/diastolic), and waist circumference (WC). We performed pair-wise and network meta-analyses with outcomes reported as weighted and standardized mean differences. Quality of evidence was rated using GRADE (Grading of Recommendations Assessment, Development and Evaluation).
RESULTS
In a meta-analysis of 28 randomized controlled trials (29,018 participants; median body mass index, 36.1 kg/m), we associated weight-loss medications with a modest decrease in FBG (weighted mean difference, 4.0 mg/dL; 95% confidence interval, -4.4 to -3.6 mg/dL) and WC (weighted mean difference, reduction of 3.3 cm; 95% confidence interval, -3.5 to -3.1 cm), without clinically meaningful changes in systolic/diastolic BP or cholesterol profile vs placebo (standardized mean difference <0.2); effects varied among drugs. Phentermine-topiramate use was associated with a substantial decrease in WC and a modest decrease in FBG, hemoglobin A1c, and BP, and had minimal effect on cholesterol. Liraglutide use was associated with a substantial decrease in FBG, hemoglobin A1c, and WC, and a minimal effect on BP and cholesterol. Naltrexone-bupropion use was associated with moderate increase in high-density lipoprotein cholesterol, but had a minimal effect on FBG and WC. Orlistat use was associated with a decrease in low-density lipoprotein and high-density lipoprotein cholesterol. No drug improved all cardiometabolic risk factors.
CONCLUSIONS
In a systematic review and network meta-analysis, we found Food and Drug Administration-approved weight-loss medications to have only modest positive effects on cardiometabolic risk profile. Further research is needed to evaluate the long-term cardiometabolic benefits of these medications.
PROSPERO
CRD42016039486.
Topics: Adult; Anti-Obesity Agents; Biomarkers; Blood Glucose; Blood Pressure; Female; Glycated Hemoglobin; Humans; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Protective Factors; Risk Assessment; Risk Factors; Treatment Outcome; Waist Circumference; Weight Loss
PubMed: 29305933
DOI: 10.1053/j.gastro.2017.12.024 -
The Cochrane Database of Systematic... Nov 2016Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Child and adolescent obesity has increased globally, and can be associated with significant short- and long-term health consequences.
OBJECTIVES
To assess the efficacy of drug interventions for the treatment of obesity in children and adolescents.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, PubMed (subsets not available on Ovid), LILACS as well as the trial registers ICTRP (WHO) and ClinicalTrials.gov. Searches were undertaken from inception to March 2016. We checked references and applied no language restrictions.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) of pharmacological interventions for treating obesity (licensed and unlicensed for this indication) in children and adolescents (mean age under 18 years) with or without support of family members, with a minimum of three months' pharmacological intervention and six months' follow-up from baseline. We excluded interventions that specifically dealt with the treatment of eating disorders or type 2 diabetes, or included participants with a secondary or syndromic cause of obesity. In addition, we excluded trials which included growth hormone therapies and pregnant participants.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data following standard Cochrane methodology. Where necessary we contacted authors for additional information.
MAIN RESULTS
We included 21 trials and identified eight ongoing trials. The included trials evaluated metformin (11 trials), sibutramine (six trials), orlistat (four trials), and one trial arm investigated the combination of metformin and fluoxetine. The ongoing trials evaluated metformin (four trials), topiramate (two trials) and exenatide (two trials). A total of 2484 people participated in the included trials, 1478 participants were randomised to drug intervention and 904 to comparator groups (91 participants took part in two cross-over trials; 11 participants not specified). Eighteen trials used a placebo in the comparator group. Two trials had a cross-over design while the remaining 19 trials were parallel RCTs. The length of the intervention period ranged from 12 weeks to 48 weeks, and the length of follow-up from baseline ranged from six months to 100 weeks.Trials generally had a low risk of bias for random sequence generation, allocation concealment and blinding (participants, personnel and assessors) for subjective and objective outcomes. We judged approximately half of the trials as having a high risk of bias in one or more domain such as selective reporting.The primary outcomes of this review were change in body mass index (BMI), change in weight and adverse events. All 21 trials measured these outcomes. The secondary outcomes were health-related quality of life (only one trial reported results showing no marked differences; very low certainty evidence), body fat distribution (measured in 18 trials), behaviour change (measured in six trials), participants' views of the intervention (not reported), morbidity associated with the intervention (measured in one orlistat trial only reporting more new gallstones following the intervention; very low certainty evidence), all-cause mortality (one suicide in the orlistat intervention group; low certainty evidence) and socioeconomic effects (not reported).Intervention versus comparator for mean difference (MD) in BMI change was -1.3 kg/m (95% confidence interval (CI) -1.9 to -0.8; P < 0.00001; 16 trials; 1884 participants; low certainty evidence). When split by drug type, sibutramine, metformin and orlistat all showed reductions in BMI in favour of the intervention.Intervention versus comparator for change in weight showed a MD of -3.9 kg (95% CI -5.9 to -1.9; P < 0.00001; 11 trials; 1180 participants; low certainty evidence). As with BMI, when the trials were split by drug type, sibutramine, metformin and orlistat all showed reductions in weight in favour of the intervention.Five trials reported serious adverse events: 24/878 (2.7%) participants in the intervention groups versus 8/469 (1.7%) participants in the comparator groups (risk ratio (RR) 1.43, 95% CI 0.63 to 3.25; 1347 participants; low certainty evidence). A total 52/1043 (5.0%) participants in the intervention groups versus 17/621 (2.7%) in the comparator groups discontinued the trial because of adverse events (RR 1.45, 95% CI 0.83 to 2.52; 10 trials; 1664 participants; low certainty evidence). The most common adverse events in orlistat and metformin trials were gastrointestinal (such as diarrhoea, mild abdominal pain or discomfort, fatty stools). The most frequent adverse events in sibutramine trials included tachycardia, constipation and hypertension. The single fluoxetine trial reported dry mouth and loose stools. No trial investigated drug treatment for overweight children.
AUTHORS' CONCLUSIONS
This systematic review is part of a series of associated Cochrane reviews on interventions for obese children and adolescents and has shown that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and bodyweight in obese children and adolescents. However, many of these drugs are not licensed for the treatment of obesity in children and adolescents, or have been withdrawn. Trials were generally of low quality with many having a short or no post-intervention follow-up period and high dropout rates (overall dropout of 25%). Future research should focus on conducting trials with sufficient power and long-term follow-up, to ensure the long-term effects of any pharmacological intervention are comprehensively assessed. Adverse events should be reported in a more standardised manner specifying amongst other things the number of participants experiencing at least one adverse event. The requirement of regulatory authorities (US Food and Drug Administration and European Medicines Agency) for trials of all new medications to be used in children and adolescents should drive an increase in the number of high quality trials.
Topics: Adolescent; Anti-Obesity Agents; Body Mass Index; Child; Cyclobutanes; Fluoxetine; Humans; Lactones; Metformin; Orlistat; Pediatric Obesity; Randomized Controlled Trials as Topic
PubMed: 27899001
DOI: 10.1002/14651858.CD012436 -
JAMA Jun 2016Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Five medications have been approved for the management of obesity, but data on comparative effectiveness are limited.
OBJECTIVE
To compare weight loss and adverse events among drug treatments for obesity using a systematic review and network meta-analysis.
DATA SOURCES
MEDLINE, EMBASE, Web of Science, Scopus, and Cochrane Central from inception to March 23, 2016; clinical trial registries.
STUDY SELECTION
Randomized clinical trials conducted among overweight and obese adults treated with US Food and Drug Administration-approved long-term weight loss agents (orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, or liraglutide) for at least 1 year compared with another active agent or placebo.
DATA EXTRACTION AND SYNTHESIS
Two investigators identified studies and independently abstracted data using a predefined protocol. A Bayesian network meta-analysis was performed and relative ranking of agents was assessed using surface under the cumulative ranking (SUCRA) probabilities. Quality of evidence was assessed using GRADE criteria.
MAIN OUTCOMES AND MEASURES
Proportions of patients with at least 5% weight loss and at least 10% weight loss, magnitude of decrease in weight, and discontinuation of therapy because of adverse events at 1 year.
RESULTS
Twenty-eight randomized clinical trials with 29 018 patients (median age, 46 years; 74% women; median baseline body weight, 100.5 kg; median baseline body mass index, 36.1) were included. A median 23% of placebo participants had at least 5% weight loss vs 75% of participants taking phentermine-topiramate (odds ratio [OR], 9.22; 95% credible interval [CrI], 6.63-12.85; SUCRA, 0.95), 63% of participants taking liraglutide (OR, 5.54; 95% CrI, 4.16-7.78; SUCRA, 0.83), 55% taking naltrexone-bupropion (OR, 3.96; 95% CrI, 3.03-5.11; SUCRA, 0.60), 49% taking lorcaserin (OR, 3.10; 95% CrI, 2.38-4.05; SUCRA, 0.39), and 44% taking orlistat (OR, 2.70; 95% CrI, 2.34-3.09; SUCRA, 0.22). All active agents were associated with significant excess weight loss compared with placebo at 1 year-phentermine-topiramate, 8.8 kg (95% CrI, -10.20 to -7.42 kg); liraglutide, 5.3 kg (95% CrI, -6.06 to -4.52 kg); naltrexone-bupropion, 5.0 kg (95% CrI, -5.94 to -3.96 kg); lorcaserin, 3.2 kg (95% CrI, -3.97 to -2.46 kg); and orlistat, 2.6 kg (95% CrI, -3.04 to -2.16 kg). Compared with placebo, liraglutide (OR, 2.95; 95% CrI, 2.11-4.23) and naltrexone-bupropion (OR, 2.64; 95% CrI, 2.10-3.35) were associated with the highest odds of adverse event-related treatment discontinuation. High attrition rates (30%-45% in all trials) were associated with lower confidence in estimates.
CONCLUSIONS AND RELEVANCE
Among overweight or obese adults, orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide, compared with placebo, were each associated with achieving at least 5% weight loss at 52 weeks. Phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss.
Topics: Anti-Obesity Agents; Bayes Theorem; Benzazepines; Drug Combinations; Female; Fructose; Humans; Lactones; Liraglutide; Male; Middle Aged; Naltrexone; Obesity; Orlistat; Phentermine; Randomized Controlled Trials as Topic; Topiramate; Weight Loss
PubMed: 27299618
DOI: 10.1001/jama.2016.7602