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Trials Apr 2016The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The quality of harms reporting in journal publications is often poor, which can impede the risk-benefit interpretation of a clinical trial. Clinical study reports can provide more reliable, complete, and informative data on harms compared to the corresponding journal publication. This case study compares the quality and quantity of harms data reported in journal publications and clinical study reports of orlistat trials.
METHODS
Publications related to clinical trials of orlistat were identified through comprehensive literature searches. A request was made to Roche (Genentech; South San Francisco, CA, USA) for clinical study reports related to the orlistat trials identified in our search. We compared adverse events, serious adverse events, and the reporting of 15 harms criteria in both document types and compared meta-analytic results using data from the clinical study reports against the journal publications.
RESULTS
Five journal publications with matching clinical study reports were available for five independent clinical trials. Journal publications did not always report the complete list of identified adverse events and serious adverse events. We found some differences in the magnitude of the pooled risk difference between both document types with a statistically significant risk difference for three adverse events and two serious adverse events using data reported in the clinical study reports; these events were of mild intensity and unrelated to the orlistat. The CONSORT harms reporting criteria were often satisfied in the methods section of the clinical study reports (70-90 % of the methods section criteria satisfied in the clinical study reports compared to 10-50 % in the journal publications), but both document types satisfied 80-100 % of the results section criteria, albeit with greater detail being provided in the clinical study reports.
CONCLUSIONS
In this case study, journal publications provided insufficient information on harms outcomes of clinical trials and did not specify that a subset of harms data were being presented. Clinical study reports often present data on harms, including serious adverse events, which are not reported or mentioned in the journal publications. Therefore, clinical study reports could support a more complete, accurate, and reliable investigation, and researchers undertaking evidence synthesis of harm outcomes should not rely only on incomplete published data that are presented in the journal publications.
Topics: Anti-Obesity Agents; Bibliometrics; Clinical Trials as Topic; Guidelines as Topic; Humans; Lactones; Orlistat; Patient Harm; Periodicals as Topic; Research Design; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 27103582
DOI: 10.1186/s13063-016-1327-z -
British Journal of Clinical Pharmacology May 2016To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of... (Meta-Analysis)
Meta-Analysis Review
AIMS
To conduct a systematic review and meta-analysis of relevant randomized clinical trials (RCTs) to ascertain the effect size of orlistat in modulating plasma levels of adipokines, ghrelin and C-reactive protein (CRP).
METHODS
Medline, SCOPUS, Web of Science and Google Scholar databases were searched. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Heterogeneity was quantitatively assessed using I(2) index. Sensitivity analyses were conducted using the one-study remove approach. Random-effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of duration of treatment, percentage change in body mass index (BMI) and baseline BMI values as potential confounders of the estimated effect size.
RESULTS
Meta-analysis suggested a significant increase in plasma levels of adiponectin [weighted mean difference (WMD): 19.18%, 95% confidence interval (CI): 5.80, 32.57, p = 0.005] and significant reductions in plasma levels of leptin (WMD: -13.24%, 95% CI: -20.69, -5.78, p = 0.001) and CRP (WMD: -11.52%, 95% CI: -16.55, -6.49, p < 0.001) following treatment with orlistat. In meta-regression, changes in plasma concentrations of adiponectin, leptin and CRP were associated with duration of treatment, but not with either change in BMI or baseline BMI values.
CONCLUSION
Orlistat is effective in increasing plasma concentrations of adiponectin and decreasing those of leptin and CRP.
Topics: Adiponectin; Anti-Obesity Agents; Body Weight; C-Reactive Protein; Ghrelin; Humans; Lactones; Leptin; Metabolic Syndrome; Orlistat; Randomized Controlled Trials as Topic
PubMed: 26717446
DOI: 10.1111/bcp.12874 -
Obesity Reviews : An Official Journal... Dec 2015Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat... (Meta-Analysis)
Meta-Analysis Review
Effect of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.
Orlistat is an effective adjunctive treatment to lifestyle modifications in the treatment of obesity. While the majority of current evidence is on the effect of orlistat in obese patients without diabetes, some studies suggest that patients who are obese and have diabetes mellitus lose more weight and have greater improvements in diabetic outcomes when treated with orlistat plus a lifestyle intervention than when treated by lifestyle interventions alone. The aim of this study was to review the evidence of the effects of orlistat on glycaemic control in overweight and obese patients with type 2 diabetes. A systematic review of randomized controlled trials of orlistat in people with type 2 diabetes reporting diabetes outcomes in studies published between January 1990 and September 2013 was conducted. We searched for articles published in English in MEDLINE and EMBASE. Inclusion criteria included all randomized controlled trials of orlistat carried out on adult participants with a body mass index of 25 kg m(-2) or over diagnosed with type 2 diabetes, which reported weight change and at least one diabetic outcome. A total of 765 articles were identified out of which 12 fulfilled the inclusion criteria. The overall mean weight reduction (3, 6 and 12 months) in the orlistat group was -4.25 kg (95% CI: -4.5 to -3.9 kg). The mean weight difference between treatment and control groups was -2.10 kg (95% CI: -2.3 to -1.8 kg, P < 0.001), the mean HbA1c difference was -6.12 mmol mol(-1) (95% CI: -10.3 to -1.9 mmol mol(-1) , P < 0.004) and the mean fasting blood glucose difference was -1.16 mmol L(-1) (95% CI: -1.4 to -0.8 mmol L(-1) , P < 0.001). Treatment with orlistat plus lifestyle intervention resulted in significantly greater weight loss and improved glycaemic control in overweight and obese patients with type 2 diabetes compared with lifestyle intervention alone.
Topics: Adult; Anti-Obesity Agents; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diet, Reducing; Glycated Hemoglobin; Humans; Lactones; Obesity; Orlistat; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Treatment Outcome; Weight Loss
PubMed: 26345590
DOI: 10.1111/obr.12318 -
American Journal of Men's Health Jul 2017Men are underrepresented in obesity services, suggesting current weight loss service provision is suboptimal. This systematic review evaluated evidence-based strategies... (Review)
Review
Men are underrepresented in obesity services, suggesting current weight loss service provision is suboptimal. This systematic review evaluated evidence-based strategies for treating obesity in men. Eight bibliographic databases and four clinical trials' registers were searched to identify randomized controlled trials (RCTs) of weight loss interventions in men only, with mean/median body mass index of ≥30 kg/m (or ≥28 kg/m with cardiac risk factors), with a minimum mean/median duration of ≥52 weeks. Interventions included diet, physical activity, behavior change techniques, orlistat, or combinations of these; compared against each other, placebo, or a no intervention control group; in any setting. Twenty-one reports from 14 RCTs were identified. Reducing diets produced more favorable weight loss than physical activity alone (mean weight change after 1 year from a reducing diet compared with an exercise program -3.2 kg, 95% confidence interval -4.8 to -1.6 kg, reported p < .01). The most effective interventions combined reducing diets, exercise, and behavior change techniques (mean difference in weight at 1 year compared with no intervention was -4.9 kg, 95% confidence interval -5.9 to -4.0, reported p < .0001). Group interventions produced favorable weight loss results. The average reported participant retention rate was 78.2%, ranging from 44% to 100% retention, indicating that, once engaged, men remained committed to a weight loss intervention. Weight loss for men is best achieved and maintained with the combination of a reducing diet, increased physical activity, and behavior change techniques. Strategies to increase engagement of men with weight loss services to improve the reach of interventions are needed.
Topics: Body Mass Index; Evidence-Based Medicine; Humans; Male; Men; Obesity; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss
PubMed: 26130729
DOI: 10.1177/1557988315587550 -
Obesity Research & Clinical Practice 2016We systematically reviewed the randomised controlled trial (RCT) evidence for long-term (≥12 months) weight management interventions for obese men in contrast to women... (Meta-Analysis)
Meta-Analysis Review
Should weight loss and maintenance programmes be designed differently for men? A systematic review of long-term randomised controlled trials presenting data for men and women: The ROMEO project.
We systematically reviewed the randomised controlled trial (RCT) evidence for long-term (≥12 months) weight management interventions for obese men in contrast to women to help understand whether programmes should be designed differently for men. We searched 11 databases up to October 2014. Twenty-two RCTs reported data separately for men and women in weight loss or weight maintenance interventions. We found men were under-represented in RCTs of weight loss interventions open to both sexes. Men comprised 36% of participants (4771 from 13,305 participants). Despite this, men were 11% (95% CI 8-14%, p<0.001) more likely to be trial completers compared to women. The trials did not report service user consultation and none were designed to investigate whether men and women responded differently to given interventions. Our meta-analysis of 13 trials showed no significant difference in weight loss between men and women, either for weight loss in kg (p=0.90) or percentage weight loss (p=0.78), although men tended to lose more weight with intensive low fat reducing diets, with or without meal replacements, and structured physical activity/exercise programmes than women. Orlistat was less beneficial for men for weight maintenance. Individual support and tailoring appeared more helpful for men than women. We found evidence that men and women respond differently to, and have different preferences for, varying types of weight management programme. We suggest that it is important to understand men's views on weight loss, as this is likely to also improve the uptake and effectiveness of programmes for men.
Topics: Anti-Obesity Agents; Behavior Therapy; Databases, Factual; Diet, Fat-Restricted; Diet, Healthy; Diet, Reducing; Exercise; Female; Health Behavior; Humans; Lactones; Male; Obesity; Orlistat; Randomized Controlled Trials as Topic; Sex Factors; Weight Loss; Weight Reduction Programs
PubMed: 25937165
DOI: 10.1016/j.orcp.2015.04.005 -
CMAJ Open 2015Childhood obesity is a public health concern. One-third of North American children and youth are overweight or obese. We reviewed the evidence of behavioural and...
BACKGROUND
Childhood obesity is a public health concern. One-third of North American children and youth are overweight or obese. We reviewed the evidence of behavioural and pharmacological weight-management interventions on body mass index (BMI), BMI z-score and the prevalence of overweight and obesity in children and youth.
METHODS
We updated the search of a previous review. We searched 4 databases up to August 2013. We included randomized trials of primary care-relevant behavioural (diet, exercise, lifestyle) and pharmacological (orlistat) interventions for treating overweight and obesity in children and youth aged 2-18 years if 6-month post-baseline data were provided for BMI, BMI z-score or prevalence of overweight and obesity. In addition, we examined secondary health outcomes such as lipid and glucose levels, blood pressure, quality of life and physical fitness. We included any study reporting harms. We performed meta-analyses when possible, and we examined the features of interventions that showed benefits.
RESULTS
Thirty-one studies (29 behavioural, 2 pharmacological and behavioural) were included. Both intervention types showed a significant effect on BMI or BMI z-score in favour of treatment (behavioural: standardized mean difference [SMD] -0.54, 95% confidence interval [CI] -0.73 to -0.36; orlistat plus behavioural: SMD -0.43, 95% CI -0.60 to -0.25). Studies reported no significant difference between groups in the likelihood of reduced prevalence of overweight or overweight and obesity. Pooled estimates for blood pressure and quality of life showed significant benefits in favour of treatment (systolic blood pressure mean difference [MD] -3.42, 95% CI -6.65 to -0.29; diastolic blood pressure MD -3.39, 95% CI -5.17 to -1.60; quality of life MD 2.10, 95% CI 0.60 to 3.60). Gastrointestinal difficulties were more common in youth taking orlistat than in the control group (risk ratio 3.77, 95% CI 2.56 to 5.55). We saw much variability across efficacious interventions.
INTERPRETATION
Low- to moderate-quality evidence suggests behavioural treatments are associated with a medium effect in terms of reduced BMI or BMI z-score compared with a small effect shown by combined pharmacological-behavioural interventions. Future research should evaluate active weight maintenance interventions in adolescents with longer follow-up and examine the effectiveness of combined pharmacological and behavioural interventions.
REGISTRATION
PROSPERO no. CRD42012002754.
PubMed: 25844368
DOI: 10.9778/cmajo.20140047 -
CMAJ Open Oct 2014Obesity is a major public health issue. This review updates the evidence on the effectiveness of behavioural and pharmacologic treatments for overweight and obesity in...
BACKGROUND
Obesity is a major public health issue. This review updates the evidence on the effectiveness of behavioural and pharmacologic treatments for overweight and obesity in adults.
METHODS
We updated the search conducted in a previous review. Randomized trials of primary-care-relevant behavioural (diet, exercise and lifestyle) and pharmacologic (orlistat and metformin) with or without behavioural treatments in overweight and obese adults were included if 12-month, postbaseline data were provided for weight outcomes. Studies reporting harms were included regardless of design. Data were extracted and pooled wherever possible for 5 weight outcomes, 6 secondary health outcomes and 4 adverse events categories.
RESULTS
We identified 68 studies, most consisted of short-term (≤ 12 mo) treatments using diet (n = 8), exercise (n = 4), diet and exercise (n = 10), lifestyle (n = 19), orlistat (n = 25) or metformin (n = 4). Compared with the control groups, intervention participants had a greater weight loss of -3.02 kg (95% confidence interval [CI] -3.52 to -2.52), a greater reduction in waist circumference of -2.78 cm (95% CI -3.34 to -2.22) and a greater reduction in body mass index of -1.11 kg/m(2) (95% CI -1.39 to -0.84). The relative risk for loss of ≥ 5% body weight was 1.77 (95% CI 1.58-1.99, [number needed to treat 5, 95% CI 4-7]), and the relative risk for loss of ≥ 10% body weight was 1.91 (95% CI 1.69-2.16, [number needed to treat 9, 95% CI 7-12]). Incidence of type 2 diabetes was lower among pre-diabetic intervention participants (relative risk 0.62 [95% CI 0.50-0.77], number needed to treat 17 [95% CI 13-29]). With prevalence rates for type 2 diabetes on the rise, weight loss coupled with a reduction in the incidence of type 2 diabetes could potentially have a significant benefit on population health and a possible reduction in need for drug treatments for glycemic control.
INTERPRETATION
There is moderate quality evidence that behavioural and pharmacologic plus behvioural, treatments for overweight and obesity in adults lead to clinically important reductions in weight and incidence of type 2 diabetes in pre-diabetic populations.
REGISTRATION
PROSPERO no. CRD42012002753.
PubMed: 25485258
DOI: 10.9778/cmajo.20140012 -
BMJ (Clinical Research Ed.) May 2014To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review and describe currently available approaches to supporting maintenance of weight loss in obese adults and to assess the evidence for the effectiveness of these interventions.
DESIGN
Systematic review with meta-analysis.
DATA SOURCES
Medline, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials.
STUDY SELECTION
Studies were identified through to January 2014. Randomised trials of interventions to maintain weight loss provided to initially obese adults (aged ≥ 18) after weight loss of ≥ 5% body weight with long term (≥ 12 months) follow-up of weight change (main outcome) were included.
STUDY APPRAISAL AND SYNTHESIS
Potential studies were screened independently and in duplicate; study characteristics and outcomes were extracted. Meta-analyses were conducted to estimate the effects of interventions on weight loss maintenance with the inverse variance method and a random effects model. Results are presented as mean differences in weight change, with 95% confidence intervals.
RESULTS
45 trials involving 7788 individuals were included. Behavioural interventions focusing on both food intake and physical activity resulted in an average difference of -1.56 kg (95% confidence interval -2.27 to -0.86 kg; 25 comparisons, 2949 participants) in weight regain compared with controls at 12 months. Orlistat combined with behavioural interventions resulted in a -1.80 kg (-2.54 to -1.06; eight comparisons, 1738 participants) difference compared with placebo at 12 months. All orlistat studies reported higher frequencies of adverse gastrointestinal events in the experimental compared with placebo control groups. A dose-response relation for orlistat treatment was found, with 120 mg doses three times a day leading to greater weight loss maintenance (-2.34 kg, -3.03 to -1.65) compared with 60 mg and 30 mg three times a day (-0.70 kg, 95% confidence interval -1.92 to 0.52), P=0.02.
CONCLUSIONS
Behavioural interventions that deal with both diet and physical activity show small but significant benefits on weight loss maintenance.
Topics: Behavior Therapy; Body Weight; Diet, Reducing; Exercise; Health Behavior; Humans; Obesity; Randomized Controlled Trials as Topic; Time Factors; Treatment Outcome; Weight Loss
PubMed: 25134100
DOI: 10.1136/bmj.g2646 -
Obesity (Silver Spring, Md.) Sep 2014To estimate the incremental cost-effectiveness of clinically proven nonsurgical commercial weight loss strategies for those with BMIs between 25 and 40. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To estimate the incremental cost-effectiveness of clinically proven nonsurgical commercial weight loss strategies for those with BMIs between 25 and 40.
METHODS
We performed a systematic literature review to identify randomized controlled trials of commercially available weight loss studies of at least 1 year in duration. Using the results of these trials and publicly available cost data, we quantified the incremental cost per kilogram of weight loss and per quality adjusted life year (QALY) gained. We then use probabilistic sensitivity analyses to quantify uncertainty in our results.
RESULTS
Based on the literature review, two lifestyle programs (Weight Watchers and Vtrim), one meal replacement program (Jenny Craig), and three pharmaceutical products (Qsymia, Lorcaserin, and Orlistat) were included in the analysis. Average cost per kilogram of weight lost ranged from $155 (95% CI: $110-$218) for Weight Watchers to $546 (95% CI: $390-$736) for Orlistat. The incremental cost per QALY gained for Weight Watchers and Qsymia was $34,630 and $54,130, respectively. All other interventions were prohibitively expensive or inferior in that weight loss could be achieved at a lower cost through one or a combination of the other strategies.
CONCLUSIONS
Results suggest that, in the absence of other considerations and at current market prices, Weight Watchers and Qsymia represent the two most cost-effective strategies for nonsurgical weight loss.
Topics: Body Weight; Cost-Benefit Analysis; Humans; Obesity; Practice Guidelines as Topic; Weight Loss
PubMed: 24962106
DOI: 10.1002/oby.20824 -
JAMA Jan 2014Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone. (Review)
Review
IMPORTANCE
Thirty-six percent of US adults are obese, and many cannot lose sufficient weight to improve health with lifestyle interventions alone.
OBJECTIVE
To conduct a systematic review of medications currently approved in the United States for obesity treatment in adults. We also discuss off-label use of medications studied for obesity and provide considerations for obesity medication use in clinical practice.
EVIDENCE REVIEW
A PubMed search from inception through September 2013 was performed to find meta-analyses, systematic reviews, and randomized, placebo-controlled trials for currently approved obesity medications lasting at least 1 year that had a primary or secondary outcome of body weight change, included at least 50 participants per group, reported at least 50% retention, and reported results on an intention-to-treat basis. Studies of medications approved for other purposes but tested for obesity treatment were also reviewed.
FINDINGS
Obesity medications approved for long-term use, when prescribed with lifestyle interventions, produce additional weight loss relative to placebo ranging from approximately 3% of initial weight for orlistat and lorcaserin to 9% for top-dose (15/92 mg) phentermine plus topiramate-extended release at 1 year. The proportion of patients achieving clinically meaningful (at least 5%) weight loss ranges from 37% to 47% for lorcaserin, 35% to 73% for orlistat, and 67% to 70% for top-dose phentermine plus topiramate-extended release. All 3 medications produce greater improvements in many cardiometabolic risk factors than placebo, but no obesity medication has been shown to reduce cardiovascular morbidity or mortality. Most prescriptions are for noradrenergic medications, despite their approval only for short-term use and limited data for their long-term safety and efficacy.
CONCLUSIONS AND RELEVANCE
Medications approved for long-term obesity treatment, when used as an adjunct to lifestyle intervention, lead to greater mean weight loss and an increased likelihood of achieving clinically meaningful 1-year weight loss relative to placebo. By discontinuing medication in patients who do not respond with weight loss of at least 5%, clinicians can decrease their patients' exposure to the risks and costs of drug treatment when there is little prospect of long-term benefit.
Topics: Anti-Obesity Agents; Humans; Life Style; Obesity; Off-Label Use; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss
PubMed: 24231879
DOI: 10.1001/jama.2013.281361