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You are here: HomeRecommendations for Primary Care PracticePublished RecommendationsRecommendation SummaryOther Supporting Document : Final Evidence Summary

Final Evidence Summary

Other Supporting Document for Obesity in Adults: Screening and Management

Preface

Release Date: October 2011


By Erin S. LeBlanc, MD, MPH; Elizabeth O’Connor, PhD; Evelyn P. Whitlock, MD, MPH; Carrie D. Patnode, PhD, MPH; and Tanya Kapka, MD, MPH


The information in this article is intended to help clinicians, employers, policymakers, and others make informed decisions about the provision of health care services. This article is intended as a reference and not as a substitute for clinical judgment.

This article may be used, in whole or in part, as the basis for the development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

This article was first published in Annals of Internal Medicine on October 4, 2011 (Ann Intern Med 2011;155:434-447; http://www.annals.org).

Abstract

Background: Overweight and obesity in adults are common and adversely affect health.

Purpose: To summarize effectiveness and harms of primary care–relevant weight-loss interventions for overweight and obese adults.

Data Sources: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2005 to September 2010; systematic reviews for identifying trials before 2005.

Study Selection: Two investigators appraised 6498 abstracts and 648 articles. Clinical trials were included if control groups received minimal interventions. Articles were rated as good, fair, or poor by using design-specific criteria.

Data Extraction: One investigator abstracted study characteristics and findings for good- and fair-quality studies; a second checked them.

Data Synthesis: Behaviorally based treatment resulted in 3-kg (6.6-lb) greater weight loss in intervention than control participants after 12 to 18 months, with more treatment sessions associated with greater loss. Limited data suggest weight-loss maintenance for 1 year or more. Orlistat plus behavioral intervention resulted in 3-kg (6.6-lb) more weight loss than did placebo after 12 months. Metformin resulted in less weight loss. Data on effects of weight-loss treatment on long-term health outcomes (for example, death and cardiovascular disease) were insufficient. Weight-loss treatment reduced diabetes incidence in participants with prediabetes. Effects on intermediate outcomes (for example, lipids and blood pressure) were mixed and small. Data on serious medication harms were insufficient. Medications commonly caused withdrawals due to gastrointestinal symptoms.

Limitations: Few studies reported health outcomes. Behaviorally based treatments were heterogeneous and specific elements were not well-described. Many studies could not be pooled because of insufficient reporting of variance data. Medication trials had high attrition, lacked postdiscontinuation data, and were inadequately powered for rare adverse effects.

Conclusion: Behaviorally based treatments are safe and effective for weight loss and maintenance.

Primary Funding Source: Agency for Healthcare Research and Quality

Introduction

The prevalence of adult obesity—defined as a body mass index (BMI) greater than 30 kg/m2—is high in the United States, exceeding 30% in most age- and sex-specific groups. In 2007–2008, 32% of men and 36% of women were obese. In addition, 40% of men and 28% of women met overweight criteria (BMI >25 kg/m2)1. The prevalence of obesity and of overweight have increased by 134% and 48%, respectively, since 1976–1980.2

Obesity is associated with increased mortality (particularly in adults <65 years)3–5, coronary heart disease (6), type 2 diabetes7, some types of cancer (8), and many other deleterious effects9. Whether being overweight is associated with an increased mortality risk is less clear, possibly because the association varies by sex, ethnicity, and age and depends on the obesity measure used (for example, BMI vs. waist circumference)10–12. Maternal obesity is associated with pregnancy complications and adverse fetal and neonatal health outcomes13.

In 2003, the U.S. Preventive Services Task Force (USPSTF) recommended that clinicians screen all adults for obesity and offer intensive counseling and behavioral interventions to promote sustained weight loss for obese adults (B recommendation: high certainty that net benefit was moderate or moderate certainty that net benefit was moderate to substantial). The USPSTF, however, concluded that evidence was insufficient to recommend for or against moderate- or low-intensity counseling together with behavioral interventions to promote sustained weight loss in obese adults (I recommendation: insufficient evidence to assess benefit and harm balance). The USPSTF concluded that evidence was insufficient to recommend for or against counseling of any intensity and/or behavioral interventions to promote sustained weight loss in overweight adults (I recommendation).

We undertook this systematic review to help update these recommendations. To conduct it, we developed an analytic framework with 4 key questions (Appendix Figure 1). The first was whether primary care screening programs to identify obesity or overweight in adults improved health or physiologic outcomes or resulted in weight loss. The other questions asked whether primary care feasible or referable weight-loss interventions (behaviorally based, with or without pharmacologic adjuncts) improved health outcomes, improved physiologic outcomes, resulted in short-term (12 to 18 months) or long-term (>18 months) weight loss, or caused harm.

Methods

The full report 9 describes our methods in detail.

Data Sources and Searches

We relied on existing reviews to cover part of the search window from the previous USPSTF review, following previously detailed guidance14. We identified a 2006 National Institute for Clinical Excellence systematic review on behavioral weight-loss interventions and orlistat15 and a 2008 review of metformin trials16. Their inclusion and exclusion criteria were congruent with ours, and investigators for both searched multiple databases and examined reference lists of pertinent reports. The reviews’ search and selection strategies were judged acceptable to substitute for ours through 2005. We bridge-searched MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials from 2005 through 9 September 2010. We supplemented our search with relevant existing systematic reviews identified through databases (Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and MEDLINE) and Web sites (Institute of Medicine, National Institutes of Health, and National Institute for Health and Clinical Excellence). We supplemented our searches with experts’ suggestions and reference lists from relevant publications, including evaluating all studies from the previous USPSTF review17.

Study Selection

Two investigators independently reviewed 6498 abstracts and 648 articles against prespecified inclusion and exclusion criteria (Appendix Figure 2). For key questions 1 to 3, we included randomized or controlled clinical trials with interventions focused on weight loss in adults (age ≥18 years) conducted in settings relevant to primary care (studies conducted in primary care or those that could in theory be implemented in a health care system, to which primary care clinicians could refer patients). We defined criteria for acceptable control groups a priori so that they would represent usual care and not overlap with low-intensity intervention groups. Acceptable control groups could not receive a personalized intervention, at-home workbook materials, or advice more frequently than annually; they also could not participate in frequent weigh-ins (<3 months). Healthy lifestyle messages were considered equivalent to weight-loss messages. For harms (key question 4), we included additional study designs (large cohort studies or case–control studies; large event monitoring; systematic evidence reviews of randomized, controlled trials [RCTs] or controlled clinical trials) and did not require 12 months of follow-up.

Data Extraction and Quality Assessment

Two independent investigators appraised all included articles as good, fair, or poor quality according to design-specific criteria and USPSTF methods18. A third investigator resolved discrepancies. We assessed validity of randomization and measurement procedures, attrition, baseline characteristics, intervention fidelity, and statistical methods. Good-quality trials blinded researchers to participant randomization if they performed tasks related to assessment, had follow-up data on 90% or more of participants with fewer than a 10–percentage point difference between groups, and described anthropomorphic measurements in detail. Trials were rated poor quality and excluded if attrition was greater than 40%, was missing, or differed by more than 20% between groups (except for harms data); key baseline characteristics differed substantially between groups and were not controlled for in analyses; or outcomes were measured unequally between groups. Additional issues caused trials to be downgraded but not excluded; these included inconsistently applied interventions, selective reporting, and unclear or suboptimal blinding or randomization procedures 9. A table of excluded studies is available in our full report9.

For included studies, one investigator abstracted data on study design, setting, population characteristics, baseline health and weight, intervention characteristics, prespecified outcomes, funding source, and adverse events into standardized evidence tables9. A second investigator reviewed abstraction for accuracy.

Data Synthesis and Analysis

We conducted separate random-effects meta-analyses to estimate the effect size of behavioral and pharmacologic interventions on weight loss (expressed in kg) and intermediate health outcomes (adiposity, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and glucose). Within each intervention type, trials were grouped according to the study population’s risk status—cardiovascular risk (diabetes, dyslipidemia, hypertension), subclinical risk (prediabetes [19], borderline high lipids [20], prehypertension[21], abdominal obesity as defined by study researchers[22, 23]), and unselected/low risk—and then ordered by the behavioral intervention’s intensity (number of sessions for behavioral trials and brief or intensive behavioral component accompanying medication trials).

We assessed the presence of statistical heterogeneity among studies by using standard chi-square tests and estimated heterogeneity magnitude by using the I2 statistic24. Tests of publication bias included funnel plots and the Egger linear regression method 25 when there were 10 or more studies26.

We explored heterogeneity of the effect size for weight loss with a series of meta-regressions9. Factors we included were population risk status, recruitment strategy, retention, study focus (weight maintenance vs. loss), whether the trial was conducted in primary care, setting (United States or not), quality, and selected patient characteristics. For behavioral trials, we also examined the number of sessions during the first year and presence of several key intervention components9. For medications, we also examined the percentage retained after run-in, medication type, and intensity of accompanying behavioral intervention.

All analyses were performed by using Stata 10.0 (Stata-Corp LP, College Station, Texas).

Role of the Funding Source

We worked with 4 USPSTF liaisons at key points throughout the process to develop and refine the analytic framework, address methodological issues, and define scope. This research was funded by the Agency for Healthcare Research and Quality under a contract to support the work of the USPSTF. Agency for Healthcare Research and Quality staff provided project oversight, reviewed the draft report, and assisted in external draft report review.

Results

Key Question 1: Screening for Obesity/Overweight

We identified no trials comparing screening with not screening for adult obesity.

Key Questions 2 and 3: Benefits of Weight-Loss Interventions

We identified 58 trials of benefits of weight-loss interventions. Thirty-eight trials (13,495 participants) involved behaviorally based intervention 23, 27–64, 18 (11,256 participants) involved orlistat plus behavioral interventions65–82, and 3 (2652 participants) involved metformin plus behavioral interventions22, 27, 83. About one third of weight-loss trials could not be included in a weight-loss meta-analysis because of missing information, usually a measure of variability around the mean.

Behavioral trial participants had mean BMIs ranging from 25 to 39 kg/m2, with an average baseline BMI across all trials (weighted for sample size) of 31.9 kg/m2. Participants had mean ages of 34 to 70 years. Overall, 60% of participants were female; less than 40% of patients were nonwhite. Orlistat trial participants were 66% female, and less than 12% were nonwhite. Only 1 metformin trial reported ethnicity; 45.3% of patients were nonwhite 84. Fifty-five percent of behavioral trials and 57% of orlistat trials examined participants with clinical or subclinical cardiovascular risk factors. Metformin trials examined participants with diabetes risk factors (prediabetes or elevated waist-to-hip ratio).

Weight Loss

Behavioral treatment trials were fairly high quality, with 24% being rated “good” (Appendix Table)27, 28, 38, 53–56, 58, 61. Among those rated “fair,” allocation concealment and blinding of outcomes assessment were frequently unclear or not reported (59% and 83% of trials, respectively). Approximately 30% of fair-quality trials had follow-up of 90% or more at 12 months (Appendix Table)23, 29, 32, 40, 42, 48, 57, 60. Just over one half of all trials limited analyses to completers23, 27–30, 34, 39, 40, 43, 46, 47, 49–51, 53–55, 57, 58, 60, 62, 63, although 3 trials had low (≤3%) attrition 32, 58, 61. When data substitution was used, studies used baseline-observation-carried-forward 33, 37, 38, 42, 52, multiple imputation35, 56, last-observation-carried-forward 37, 41, 44, 59, imputation of missing data through random-effects regression35, 45, 64, multiple imputation method35, 56, or unspecified method 31, 48, 61. We did not find an association between effect size and study quality, attrition, or presence of data imputation through meta-regression.

Most trials showed that behavioral interventions had a statistically significant effect on weight loss at 12 to 18 months 23, 27–64. Controls generally lost little or no weight, whereas intervention groups lost 1.5 to 5 kg (3.3 to 11 lb), an average of 4% of baseline weight. In 21 trials that could be combined by meta-analysis, patients receiving behavioral interventions lost 3.0 kg (6.6 lb) more (95% CI, −4.0 to −2.0 kg) than controls after 12 to 18 months (Figure 1). Statistical heterogeneity was high (I2 = 95%) because the amount of weight change varied greatly. Behavioral interventions lasting longer (24 to 54 months) continued to show greater weight loss (2 to 4 kg [4.4 to 8.8 lb]) compared with controls 28, 46, 53, 55, 58, 61. Weight loss could be maintained for an additional year or more after completion of an active weight-loss phase, particularly with additional support27, 34, 39, 41, 52, 60.

Interventions with more sessions showed more weight loss—patients receiving 12 to 26 intervention sessions generally lost 4 to 7 kg (8.8 to 15.4 lb) (6% of baseline weight) compared with 1.5 to 4 kg (3.3 to 8.8 lb) (2.8% of baseline weight) in intervention groups with fewer than 12 sessions in the first year. After adjustment for number of sessions in the first year, none of the following demonstrated a relationship with effect size: physical activity sessions, group sessions, individual sessions, technology-based intervention, specific weight-loss goals, spouse or family involvement, addressing barriers to weight loss, motivational assessment (for example, pros and cons of weight loss), self-monitoring, incentives, or support after active intervention phase. However, our confidence in these null results is limited because some behavioral trials did not detail their interventions. These studies may have provided one or more components but not reported them. In addition, more intensive interventions tended to involve more components; disentangling the effect of intensity from specific components was not possible.

The orlistat data were limited in that there was only 1 good-quality trial69 (Appendix Table). Randomization procedures (including allocation concealment) and medication adherence rates were rarely reported. Only 1 study specifically stated that funding was not from a pharmaceutical company69. Only 5 studies had greater than 80% follow-up at 12 to 18 months (range, 61% to 96%)69, 72, 74, 79, 82. Follow-up in control groups was often greater than 10% lower than in orlistat groups72, 74, 79, 82. Over 70% of orlistat trials65–67, 70–73, 77–82 and 33% of metformin trials22 used last-observation-carried-forward for data substitution. The remaining analyzed only those with complete data 27, 68, 75, 83 or did not describe data substitution methods69, 74, 76. We did not note an association between effect size and attrition or presence of data imputation through meta-regression, although power and range of attrition would be somewhat limited.

Orlistat treatment with accompanying behavioral component resulted in weight loss of 5 to 10 kg (11 to 22 lb; 8% of baseline weight) compared with 3 to 6 kg (7 to 13 lb; 5% of baseline weight) with placebo and the same behavioral component65–82. Almost all orlistat trials used intensive behavioral components. In the 12 trials that could be combined by meta-analysis, participants randomly assigned to orlistat lost 3.0 kg (6.6 lb) more (95% CI, −3.9 to −2.0 kg) than those receiving placebo after 12 months (Figure 1). With 1 exception69, the studies were not highly variable. Limited data showed no dose response72, 79. Weight loss was maintained with up to 24 to 36 months of orlistat therapy 78, 79. No trials reported weight outcomes after orlistat therapy was stopped. Metformin plus a behavioral intervention was associated with a smaller degree of weight loss (2 to 4 kg [4.4 to 8.8 lb]) 22, 83, 85, although the best evidence was limited to patients with prediabetes85.

The effect of weight-loss programs among participant subgroups was sparsely reported and often mixed. Behaviorally based interventions seemed on average to lead to less weight loss in black patients and women than nonblack patients and men; effects of baseline BMI and age were mixed 30, 38, 43, 54, 56, 57, 61, 63, 86–88. Medication trials did not examine subgroups, or their findings applied only to patients with prediabetes27, 87.

Health Outcomes

Included trials did not demonstrate an effect on mortality, cardiovascular disease, hospitalizations, or depression, although data were sparse for all outcomes (Table 1)22, 27, 42, 49, 56, 58, 63, 66, 72, 79, 81, 82, 84, 89–91. The 2 good-quality trials reporting 1 or more of these health outcomes were not powered to detect group differences in any health outcomes other than depressive symptoms27, 58, 89.

Diabetes Incidence

All intervention types reduced diabetes incidence, particularly in patients with elevated risk (Table 1). Behaviorally based interventions (7 to 23 sessions in first year), which led to weight loss of 4 to 7 kg (8.8 to 15.4 lb), cut diabetes incidence by about 50% or more over 2 to 3 years 58, 84. Metformin and orlistat reduced diabetes incidence 22, 78, 82, 84. However, orlistat data may not be reliable and generalizable78, 82; by year 4, 1 trial had 48% and 68% attrition in the orlistat and placebo groups, respectively82, and the other administered orlistat after participants experienced at least 5% weight loss during an 8-week very-low-calorie diet78.

Glucose Tolerance

Behaviorally based interventions, orlistat, and metformin all led to declines in fasting glucose levels in prediabetic and diabetic patients at 12 to 18 months compared with controls31, 42, 45, 46, 49, 58, 69, 71, 74, 77, 85. Mean decreases in glucose levels were 0.30 and 0.31 mmol/L (5.4 and 5.5 mg/dL) with behavioral interventions and metformin, respectively. Glucose reductions were greater with orlistat (0.672 mmol/L [12.1 mg/dL]) greater than placebo]], possibly because those studies were conducted in diabetic patients.

Lipids

Pooled estimates for lipid changes with behavioral interventions were at high risk for reporting bias because lipid outcomes were rarely reported (Figure 2). Trials included in meta-analyses were more likely to show effects than those not included. Although some trials did find statistically significant results, effect sizes were consistently small (most had reductions in low-density lipoprotein cholesterol level ≤0.26 mmol/L [10 mg/dL]). We concluded that behavioral weight-loss interventions had low or very small effects on low-density and high-density lipoprotein cholesterol and triglyceride levels23, 29–31, 38, 41, 42, 46, 48, 49, 53, 57, 58, 62–64. Orlistat reduced low-density lipoprotein cholesterol levels by a slightly greater amount (0.29 mmol/L [11 mg/dL]) more than placebo]], but high-density lipoprotein cholesterol levels were reduced and triglyceride levels did not change65–82. Metformin did not improve lipid profiles 22, 83, 90.

Blood Pressure

Absolute reductions of 2 to 5 mm Hg in systolic and diastolic blood pressure were reported in behaviorally based and orlistat {plus behavioral intervention) trials over 12 to 36 months. When examined with meta-analyses, this translated into approximately 2–mm Hg greater decreases than control conditions after 12 to 18 months with either treatment (Figure 3])23, 29–31, 42, 49, 53–55, 57, 58, 60, 63, 67, 68, 72, 77, 79–81, 90, 91. Behavioral treatment reduced the risk for a hypertension diagnosis in participants with prehypertension (34% and 22% reduced risk at 12 and 18 months, respectively)54, 55. Metformin did not have favorable effects on blood pressure 22, 90.

Waist Circumference

Waist circumference decreased by 2.7 cm more (CI, −4.1 to −1.4 cm) in behavioral intervention groups than in control groups. Statistical heterogeneity was high (I2 = 93.8%), but most trials showed statistically significant group differences23, 30, 31, 37, 38, 41, 42, 46, 48, 49, 57, 58, 60, 85. Orlistat and metformin reduced waist circumference by 2.3 cm (CI, −3.6 to −0.9 cm) and 1.5 cm (CI, −2.0 to −1.0 cm), respectively, compared with placebo 65, 66, 68, 69, 71, 74–76, 78, 79, 81–83, 85.

Key Question 4: Harms of Weight-Loss Interventions

Behavioral Studies

Ten studies reported on possible harms of behavioral weight-loss interventions. Weight loss reduced total61 or hip53, 59 bone mineral density in 3 fair- to good-quality trials53, 59, 61. Increased physical activity did not result in serious adverse effects or injuries over 1- to 2-year interventions38, 46, 92, 93. One study reported no increased risk for eating disorder pathology in those participating in weight-loss interventions 94.

Orlistat

We included 18 RCTs from key questions 2 and 3 65–82, 5 additional published RCTs not included in key questions 2 and 3 95–99 (12,174 participants in all trials combined), and 1 United Kingdom event-monitoring study100 (16,021 persons) on the harms of orlistat (120 mg 3 times per day). Sixty-two percent of trials recruited participants with at least 1 clinical or subclinical cardiovascular risk factor65, 66, 68, 69, 71, 74, 76–78, 81, 82, 95–98. Participants were 41 to 59 years of age; 66% of patients were female, and less than 15% were nonwhite. Although median trial duration was 52 weeks, 5 trials provided data beyond 52 weeks. Participants randomly assigned to receive orlistat were more likely to experience adverse effects and withdraw from trials because of adverse effects than those assigned to placebo (Table 2)65–82, 95–99, 101. Withdrawals were primarily due to gastrointestinal symptoms. In included studies, serious adverse effects were not increased with orlistat compared with placebo 66, 68, 69, 75, 76, 78–82, 95, 96, 99. Orlistat was associated with a decrease in some fat-soluble vitamin levels compared with placebo 73, 74, 79, 82, 99. Data did not suggest that higher dosages were associated with elevated adverse effect rates, although results were mixed72, 73, 79, 99.

Metformin

We included 4 trials on harms of metformin (850 mg twice daily): 3 trials from key questions 2 and 322, 83, 86 and 1 additionally published RCT102 (2712 participants). Participants randomly assigned to receive metformin were more likely than placebo recipients to have and withdraw because of adverse events (Table 2)22, 83, 102. Gastrointestinal symptoms were the main reason for excess adverse effects22, 83, 86, 102. No studies reported serious adverse effects.

Discussion

Because we found no trials directly examining the benefits and harms of obesity screening followed by expected appropriate treatment in adults, we focused on effectiveness and harms of primary care–relevant weight-loss interventions. Behavioral treatment trials were fairly recent and of high quality. However, orlistat trials were generally lower quality. Participants in behavioral treatment trials providing 12 to 26 intervention sessions during the first year lost 4 to 7 kg (8.8 to 15.4 lb) (average, 6% of baseline weight) at 12 to 18 months, compared with little to no weight loss in control groups. Participants receiving orlistat plus intensive behaviorally based intervention lost 5 to 10 kg (11 to 22 lb) (average, 8% of baseline weight), compared with 3 to 6 kg in the placebo groups. Metformin was associated with less weight loss (2 to 4 kg [4.4 to 8.8 lb]). Long-term weight loss (>18 months) was sparsely reported, but weight loss generally persisted with continued treatment. Five percent weight loss is considered clinically meaningful and is a primary weight-loss outcome according to the U.S. Food and Drug Administration103.

Most104–107, but not all108, epidemiologic data suggest that intentional weight loss less than 9 kg is not associated with reduced mortality. Epidemiologic data, however, are mixed and confounded by several factors, particularly health status. Prospective cohort studies of patients undergoing bariatric surgery show substantial improvements in health. Weight loss with surgery, however, is generally 25 to 50 kg (55 to 110 lb.)109, 110.

Because health outcome data were insufficient, we examined the metabolic consequences of weight-loss interventions. Two fair- to good-quality trials showed that diabetes incidence was reduced by 30% to 50% with behavioral weight-loss interventions among overweight and obese patients with elevated plasma glucose levels. Behavioral weight-loss interventions had little to no effect on lipids. Improved cholesterol levels may require large amounts of weight loss111. Lowering low-density lipoprotein cholesterol levels with orlistat may reflect reduced fat absorption112. Although summary measures showed small blood pressure reductions, absolute reductions of 2 to 5 mm Hg were reported in some orlistat and behaviorally based trials over 12 to 36 months, consistent with findings of a previous meta-analysis113. Reductions in diastolic blood pressure of 5 to 6 mm Hg over 5 to 10 years have been associated with small reductions in stroke and coronary heart disease events114.

Higher treatment intensity was associated with greater weight loss, despite limitations in our measure of treatment intensity. Most higher-intensity interventions included self-monitoring, setting goals, addressing barriers to change, and strategizing about maintaining long-term changes. However, we found that no component was associated with degree of weight loss in meta-regression. Specific articulation of essential elements of effective interventions was not possible.

Methods used to measure obesity in clinical practice (for example, BMI and waist circumference) are low cost and cause no direct physical harms. Secondary harms could include labeling stigma, higher insurance premiums, or reinforcement of poor self-esteem. Misclassifying a person’s risk status is possible if current BMI cut-offs are used during screening because BMI may predict future health risk differently among various ethnic and age groups115, 116.

Weight loss may be associated with decreased bone density, but data are lacking on post–weight-loss bone density and subsequent fracture risk. The validity of measuring bone changes during weight loss is also unclear. Fat distribution changes may alter bone measurement despite stable bone117–119. Limited data suggested no increased risk for serious injuries or eating disorders.

Orlistat and metformin caused mild to moderate gastrointestinal side effects resulting in discontinuation of therapy. Our inclusion and exclusion criteria were not designed to identify rare harms. We did not find studies associating orlistat with liver, kidney, or pancreas damage, other than case reports. However, in May 2010, the U.S. Food and Drug Administration revised its label for orlistat, 120 mg (prescription) and 60 mg (over-the-counter), to include “new safety information about cases of severe liver injury that have been reported rarely with the use of this medication120. Orlistat has been recently associated with possible kidney and pancreas damage121. Indeed, antiobesity medications have a long history of removal from the market or failing U.S. Food and Drug Administration approval122–124.

Several factors limited this evidence review. Because of missing information, we could not include about one third of trials in meta-analyses. Intermediate physiologic outcomes were even less likely to be studied and available for meta-analyses. We excluded 143 studies because control groups had more than minimal interventions (considered comparative effectiveness), including Look AHEAD, a weight-loss intervention trial in diabetic patients125. Its findings were similar to and slightly more positive than the findings of included trials. Comparative-effectiveness trials would shed more light on effective intervention components and are being reviewed elsewhere 126.

Few studies were conducted in primary care. Interventions were often intensive and possibly difficult to implement in primary care settings (although providers could refer to them). No trial had a mean BMI in the class III obese range (>40 kg/m2), so generalizability to extreme obesity is unknown. Because most medication trials had run-in periods, participants were probably more motivated, adherent, and responsive than primary care populations. Our results, especially medication findings, are possibly biased by high attrition.

We did not systematically examine the best screening approach for obesity. A growing body of evidence suggests that waist-to-hip ratio or waist circumference may be better predictors of future health effects than is BMI127–135, especially for some subgroups116, 136. Systematically rereviewing the best screening tool for adult obesity should be of high priority. We did not systematically review cost-effectiveness data. The economic impact of weight-loss interventions is an important clinical consideration.

Metformin is the only off-label medication we included. Other medications used off-label for weight loss include zonisamide, an antiepileptic agent137. We did not examine antiobesity drugs in development, including lorcaserin; a combination of phentermine plus topiramate; or a combination of naltrexone plus bupropion. We did not include phentermine because it is approved only for short-term use.

In summary, we found no direct evidence on benefits and harms of primary care–based obesity screening but did find that behavioral weight-loss interventions with or without orlistat or metformin yielded clinically meaningful weight loss; however, health outcomes data were sparse.

Harms of behavioral weight-loss interventions were minimal; data were insufficient on serious harms from medications. Long-term weight and health outcomes data were lacking and should be a high priority for future study. Research should clarify which benefits are derived specifically from weight loss itself or from behavioral mediators, such as physical activity or dietary changes.

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Copyright and Source Information

Source: This article was first published in Annals of Internal Medicine (Ann Intern Med 2011;155:434-447).

Acknowledgment: The authors thank Victor Stevens, PhD, MA, for providing his expertise; Daphne Plaut, MLS, for conducting the literature searches; Kevin Lutz, MFA, for his editorial support; Caitlyn Senger, MPH, Tracy Beil, MS, Catherine Livingston, MD, MPH, and Sarah Zuber, MSW, for their assistance in conducting the evidence review; and Leslie Perdue, MPH, for her assistance in conducting the evidence review and preparing the manuscript. They also thank the Agency for Healthcare Research and Quality and the USPSTF, as well as expert reviewers David Arterburn, MD, MPH; George Bray, MD; James Hill, PhD; Robert Jeffery, PhD; and Jarl Torgerson, MD, PhD, for their contribution to this evidence review.

Grant Support: By the Oregon Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality, Rockville, Maryland (contract HHS-290-2007-10057-I, task order no. 3).

Potential Conflicts of Interest: Dr. LeBlanc: Grant (money to institution): Agency for Healthcare Research and Quality. Dr. O’Connor: Grant (money to institution): Agency for Healthcare Research and Quality; Support for travel to meetings for the study or other purposes (money to institution): Agency for Healthcare Research and Quality; Payment for writing or reviewing the manuscript (money to institution): Agency for Healthcare Research and Quality; Provision of writing assistance, medicines, equipment, or administrative support (money to institution): Agency for Healthcare Research and Quality. Dr. Kapka: Grant (money to institution): Agency for Healthcare Research and Quality; Support for travel to meetings for the study or other purposes (money to institution): Agency for Healthcare Research and Quality; Payment for writing or reviewing the manuscript (money to institution): Agency for Healthcare Research and Quality; Provision of writing assistance, medicines, equipment, or administrative support (money to institution): Agency for Healthcare Research and Quality. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-0823.

Requests for Single Reprints: Reprints are available from the U.S. Preventive Services Task Force Web site (www.uspreventiveservicestaskforce.org).

Current author addresses and author contributions are available at http://www.annals.org.

Figure 1. Difference Between Intervention and Control Groups in Weight Change at 12 to 18 Months

Text Description is shown below.

Weights are from random-effects analysis. ADAPT = Activity, Diet and Blood Pressure Trial; CV = cardiovascular; DISH = Dietary Intervention to Study Hypertension; DPP = Diabetes Prevention Program; FDPS = Finnish Diabetes Prevention Study; HEED = Help Educate to Eliminate Diabetes; HI = intensive intervention; IV = intervention; LO = brief intervention; NR = not reported; ORBIT = Obesity Reduction Black Intervention Trial; PATH = Physical Activity for Total Health; PREDIAS = Prevention of Diabetes Self-Management Program; Subclinical = trials limited to those with elevated risk but without known disease (prehypertension; impaired glucose tolerance or elevated fasting glucose; borderline high total cholesterol, low-density lipoprotein, or triglyceride levels; low high-density lipoprotein levels; abdominal obesity); TOHP = Trials of Hypertension Prevention; WHLP = Women’s Healthy Lifestyle Project; WMD = weighted mean difference.

Text Description.

Figure 1 displays a forest plot of studies reporting the weighted mean difference in weight between intervention and control groups. The meta-analysis combines the 21 weight-loss trials reporting kilograms or pounds lost at 12 to 18 months and shows an estimated average effect of 3.0 more kg lost in the intervention than control groups (95% CI,-4.0 to -2.0; I2=94.9%; k=21; n=7,343). Overweight and obese participants randomized to orlistat lost an average of 3 kg more weight than those randomized to placebo after 12 months (WMD= -3.0 [95% CI, -3.9 to -2.0; I2=84.9%; k=12]).

Table 1. Summary of Evidence for Effect of Weight-Loss Interventions on Clinical Outcomes

Outcome Trials, n Overall Quality Summary of Findings
Distal health outcomes
  Behaviorally based interventions
     Death 2 Good No differences in death rate, but small number of deaths limits conclusions
     CVD 4 Fair to good No differences in CVD events or CVD-related deaths in 3 large good-quality trials; additional fair-quality trial showed no difference in percentage taking cardiovascular medication at 1 y
    Hospitalization 1 Fair to good No differences in hospitalization, but low hospitalization rate limits conclusions
    HRQL/depression 3 Fair None of 3 trials found group differences in depression outcomes; small change in HRQL correlated with weight change in the 1 good-quality trial (DPP)
  Pharmacotherapy
    Orlistat
      Death 4 Fair Each study only had 1 death; in all studies, deaths were in the orlistat group but there was no clear relationship with treatment
      HRQL/depression 2 Fair No difference in depression scores; orlistat group had greater satisfaction with treatment, less overweight distress, and improvement on 1 of 8 subscales (vitality) of SF-36
    Metformin
      Death 2 Fair to good No difference between groups, but small number of deaths limits conclusions
      Hospitalization 1 Good No difference in hospitalization, but low hospitalization rate limits conclusions
      CVD 2 Fair to good No difference in CVD events
      HRQL/depression 1 Good No difference in depression
Intermediate health outcome
   Behaviorally based interventions
      DM 3 Good In 2 large good-quality trials, approximately twice as many participants in the control group than in the lifestyle intervention group developed DM, but no DM reduction was seen in the small trial, which had very high baseline rates of elevated fasting glucose levels
  Pharmacotherapy
    Orlistat
      DM 2 Fair Both trials reported lower incidence of diabetes (by 9-10 percentage points) in orlistat group, but we had concerns about the generalizability and reliability of these findings
    Metformin
      DM 2 Fair to good Incidence of diabetes was reduced with metformin in the good-quality trial in participants with prediabetes after 3 y (21.7% vs. 28.9%); the smaller trial with unclear adjudication also found decreased risk for diabetes in participants randomly assigned to metformin

CVD = cardiovascular disease; DM = type 2 diabetes mellitus; DPP = Diabetes Prevention Program; HRQL = health-related quality of life; SF-36 = Short Form-36.

Table 2. Summary of Medication Harms

Adverse Events Trials in Meta-analysis, Additional Trials, n, n Meta-analysis Results: Relative Risk (95% CI) Weighted Means, % Results From Studies Not in Meta-analysis Comments
Orlistat
Withdrawals due to adverse effects 23, 0 1.67 (1.32–2.13) IG: 8
CG: 4
- GI symptoms were main reason for withdrawal
Any 8, 0 1.10 (1.03–1.17) IG: 78
CG: 70
- GI symptoms were main reason for AEs
Serious 11, 2 1.21 (0.88–1.68) IG: 10
CG: 9
0 serious AEs in either treatment group in 2 trials Examples of serious events included fecal incontinence, diverticulitis, abdominal pain
GI 18, 0 1.42 (1.33–1.52) IG: 83
CG: 59
- GI symptoms were of mild to moderate intensity and often resolved spontaneously
Hypoglycemia 0, 3 - - 2 of 3 found increased incidence of hypoglycemia with orlistat -
Bone mineral density 0, 1 - - In small subsample (n = 30) of larger study, bone density did not differ between groups -
Vitamin deficiencies 0, 5 - - 5 of 5 studies found lower vitamin E with orlistat; 4 of 4 studies found lower β-carotene levels with orlistat; 1 of 2 trials found lower vitamin A levels; 1 of 1 study found lower vitamin K levels; 5 of 5 studies found that orlistat recipients required more vitamin supplementation during the study -
Liver injury 0, 1 (event
monitoring
cohort)
- - UK monitoring study reported elevated liver test results in 2 cases of 16,021 dispenses analyzed; no cases of serious hepatic adverse reactions FDA recently added warning to label to orlistat about possible risk for severe liver disease
Metformin
Withdrawals 2, 0 3.92 (1.23–12.57) IG: 5
CG: 1
- -
Any 2, 0 4.83 (0.84–27.63) IG: 46
CG: 16
- -
Serious 0 - - - -
GI 1, 3 - - Increased risk of GI AEs in metformin group Main GI symptoms included diarrhea, flatulence, nausea, vomiting
Hypoglycemia 0 - - - -
Bone density 0 - - - -

AE = adverse event; CG = control group; FDA = U.S. Food and Drug Administration; GI = gastrointestinal; IG = intervention group; UK = United Kingdom.

Figure 2. Difference Between Intervention and Control Groups in Changes in LDL Cholesterol Levels

Text Description is shown below.

Weights are from random-effects analysis. Pooled estimates for lipid changes with behavioral interventions were at high risk for reporting bias because lipid outcomes were rarely reported. To convert LDL cholesterol values to mmol/L, multiply by 0.0259.

CV = cardiovascular; HEED = Help Educate to Eliminate Diabetes; HI = intensive intervention; IV = intervention; LDL = low-density lipoprotein; LO = brief intervention; NR = not reported; PATH = Physical Activity for Total Health; Subclinical = trials limited to those with elevated risk but without known disease (prehypertension; impaired glucose tolerance or elevated fasting glucose; borderline high total cholesterol, low-density lipoprotein, or triglyceride levels; low high-density lipoprotein levels; abdominal obesity); WHLP = Women’s Healthy Lifestyle Project; WMD = weighted mean difference.

Text Description.

Figure 2 displays a forest plot of studies reporting the weighted mean difference in LDL cholesterol between the intervention and control groups. According to the meta-analysis, weight-loss intervention groups showed an average 4.9 mg/dL greater decline in LDL cholesterol (95% CI, −7.3 to −2.6; I2=0.0%; k=8; n=1,755) compared with control groups at 12 to 18 months. Overweight and obese participants in the orlistat group had a 11.4 mg/dL greater decline in LDL cholesterol (95% CI, −15.8 to -7.0; I2=86.3%; k=12; N=4,213) compared with placebo participants over 12 to 18 months.

Appendix Figure 1. Analytic Framework: Primary Care Screening and Interventions for Obesity and Overweight

KQ 1: Is there direct evidence that primary care screening programs for adult obesity or overweight improve health outcomes or result in short-term (12 to 18 mo) or sustained (>18 mo) weight loss or improved physiologic measures (i.e., glucose tolerance, blood pressure, and dyslipidemia)? a) How well is weight loss maintained after an intervention is completed?
KQ 2: Do primary care–relevant interventions (behaviorally based interventions and/or pharmacotherapy) in obese or overweight adults lead to improved health outcomes (morbidity from diabetes mellitus, cardiovascular disease, cancer, arthritis, asthma, sleep apnea, depression, emotional functioning, physical fitness capacity or performance, physical functioning, disability, mortality)? a) What are common elements of efficacious interventions? b) Are there differences in efficacy between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk)?
KQ 3: Do primary care–relevant interventions in obese or overweight adults lead to short-term or sustained weight loss, with or without improved physiologic measures? a) How well is weight loss maintained after an intervention is completed? b) What are common elements of efficacious interventions? c) Are there differences in efficacy between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk)?
KQ 4: What are the adverse effects of primary care–relevant interventions in obese or overweight adults (e.g., nutritional deficits, cardiovascular disease, bone mass loss, injuries, death)? a) Are there differences in adverse effects between patient subgroups (i.e., age 65 y or older, sex, race/ethnicity, degree of obesity, baseline cardiovascular risk status)? KQ = key question.

Text Description.

Appendix Figure 1 is an analytic framework for the key questions of this report that depicts the events that adults (18-64 years) and older adults (65 years and older) could experience while undergoing screening and interventions for obesity. In general, the figure illustrates how obesity screening in adults leads to interventions. The obesity interventions may lead to short-term or maintained weight loss, and/or improved glucose tolerance, blood pressure, and dyslipidemia. These intermediate outcomes may also lead to decreased morbidity from selected conditions, improved physical fitness, reduced disability, improved emotional functioning, and reduced mortality. The figure also depicts the possibility of harms or adverse events occurring as a result of screening or interventions.

Appendix Figure 2. Literature Search and Selection

Text Description is shown below.

KQ = key question.

Text Description.

Appendix Figure 2 shows the search results and article flow of the review. Initially, 11,875 records were identified through database searching, along with 371 records found using other search methods. After duplicates were removed, 6498 records remained and were screened by the review team. Upon review of each study abstract, 5850 records were excluded and 648 full-text articles were assessed for eligibility (22 for Key Question [KQ] 1, 583 for KQ2, 588 for KQ3, and 629 for KQ4). During full-text review, 22 publications were excluded for KQ1 (4 for relevance , 1 for setting, 1 for outcomes, 5 for interventions, 10 for design, and 1 for quality), 551 for KQ2 (64 for relevance, 17 for setting, 116 for outcomes, 59 for interventions, 265 for design, 20 for quality, and 2 for study period), 490 for KQ3 (64 for relevance, 17 for setting, 10 for population, 49 for outcomes, 61 for interventions, 266 for design, 20 for quality, and 3 for study period), and 569 for KQ4 (66 for relevance, 17 for setting, 9 for population, 197 for outcomes, 79 for interventions, 193 for design, 6 for quality, and 2 for study period). In the end, no studies were included for KQ1, 32 publications (15 trials) were included for KQ2, 98 publications (58 trials) were included for KQ3, and 60 publications (38 trials) were included for KQ4.

Appendix Table. Outcomes Reported and Quality Issues for Included Trials (Parts 1 and 2)

Part 1

Study, Year (Reference) Outcomes
Weight
Loss
Distal
Health
Outcome
DM Glucose
Tolerance
Lipids Blood
Pressure
Waist
Circumference
Adverse
Events
Behavioral trials
  With CV risk factor
    Diabetes
      Christian et al, 2008 31 XX     X XX XX XX  
      Mayer-Davis et al, 2004 45 X     X X X    
    Hypertension
      Burke et al, 2005 (ADAPT) 30 XX         XX XX  
      Cohen et al, 1991 32 XX         X    
      Davis et al, 1992 (TAIM) 34 X X       X    
      Jones et al, 1999 (HOT) 40 X         X    
      Kastarinen et al, 2002 (LIHEF) 41 X     X X X X  
      Langford et al, 1985 (DISH) 43 XX              
      Whelton et al, 1998 (DISH) 61 X X       X   X
    Multiple risk factors
      Anderssen et al, 1995 (ODES) 29 X X     X XX    
      Svetkey et al, 2008 (WLM) 56 X X            
      ter Bogt et al, 2009 57 XX     XX XX XX XX  
      Woollard et al, 2003 64 XX       X      
  Subclinical
      Parikh et al, 2010 (Project HEED) 49 XX   X XX XX XX XX  
      HPT, 1990 28 X         X    
      DPP, 2005 85 XX X X XX   XX XX X
      Stevens et al, 1993 (TOHP I) 54 XX         XX    
      Stevens et al, 2001 (TOHP II) 55 XX         XX    
      Villareal et al, 2008 59 X X   X X X   X
      Mensink et al, 2003 46 XX     XX XX   XX X
      Tuomilehto et al, 2001 58 XX X X XX XX XX XX  
      Kulzer et al, 2009 42 XX X   XX XX XX XX  
      Mitsui et al, 2008 23 X     XX XX XX XX  
  Low risk or unselected
      Cussler et al, 2008 33 X              
      Fitzgibbon et al, 2010 (ORBIT) 35 XX              
      Haapala et al, 2009 37 XX           XX  
      Irwin et al, 2003 (PATH) 38 XX     X XX   XX X
      Jeffery et al, 1993 39 X              
      Martin et al, 2008 44 XX              
      Moore et al, 2003 47 X              
      Narayan et al, 1998 48 X   X X X X X  
      Perri et al, 1988 50 X              
      Pritchard et al, 1999 51 X              
      Silva et al, 2010 52 X              
      Simkin-Silverman et al, 2003 (WHLP) 53 XX     XX XX XX    
      Werkman et al, 2010 60 XX         XX XX  
      Wood et al, 1991 63 XX X     XX XX    
      Wood et al, 1988 62 XX       XX      
Medication trials
  Orlistat
      Berne et al, 2005 65 X     X XX X XX XX
      Broom et al, 2002 66 XX     X X X X XX
      Davidson et al, 1999 67 XX     X X XX   XX
      Derosa et al, 2003 68 XX       XX XX XX XX
      Derosa et al, 2010 69 XX     XX XX   XX XX
      Finer et al, 2000 70 X     XX XX     XX
      Hanefeld and Sachse, 2002 71 XX     XX XX X XX XX
      Hauptman et al, 2000 72 XX X   XX XX XX   XX
      Hill et al, 1999 73 X     X X X   XX
      Hollander et al, 1998 74 XX     XX XX   XX XX
      Krempf et al, 2003 75 XX       X   XX XX
      Lindgärde, 2000 76 XX     XX XX XX X XX
      Miles et al, 2002 77 XX     XX XX XX   XX
      Richelsen et al, 2007 78 X   X X X X X XX
      Rössner et al, 2000 79 XX X   XX XX XX X XX
      Sjöström et al, 1998 80 X     XX XX XX   XX
      Swinburn et al, 2005 81 XX X   XX XX XX XX XX
      Torgerson et al, 2004 (XENDOS) 82 X   X X X X X XX
   Metformin
       Fontbonne et al, 1996 (BIGPRO) 22 XX X X XX XX XX   XX
      Gambineri et al, 2006 83 XX     XX XX   XX XX
      DPP, 2005 85 XX X X XX X XX XX X

Part 2

Study, Year (Reference) Allocation Concealment Quality Issues
BOA Retention* ITT Analysis Overall Quality and Other Quality Concerns or Clarifications
Behavioral trials
  With CV risk factor
    Diabetes
      Christian et al, 2008 31 Yes NR 88% Unclear Fair
Use of the term “ITT” not clear
      Mayer-Davis et al, 2004 45 NR NR 81% RER Fair
    Hypertension
      Burke et al, 2005 (ADAPT) 30 Yes NR 80% No Fair
      Cohen et al, 1991 32 NR NR 100% NA Fair
Small number of participants
      Davis et al, 1992 (TAIM) 34 Yes Yes (blood pressure)
NR (weight loss)
Unclear No Fair
Retention NR at 12 mo, 89% at 6 mo, 59% at 24 mo
      Jones et al, 1999 (HOT) 40 Unclear NR 91% No Fair
Unclear information on outcome blinding (described as “single blind”), assessment and statistical methods not well described
      Kastarinen et al, 2002 (LIHEF) 41 Yes NR 83% LOCF Fair
Retention lower in control than intervention group at 12 mo (77% vs. 88%)
      Langford et al, 1985 (DISH) 43 NR NR 82% No Fair
Attrition lower in control than intervention group (77% vs. 88%)
Minimal description of control group contact
      Whelton et al, 1998 (DISH) 61 NR Yes 98% NR Good
    Multiple risk factors
      Anderssen et al, 1995 (ODES) 29 Yes NR 95% No Fair
Lack of information about assessment blinding, but well-defined procedures probably minimized bias
      Svetkey et al, 2008 (WLM) 56 Yes Yes 95% MImp Good
      ter Bogt et al, 2009 57 NR NR 91% No Fair
Lack of information about assessment blinding, but well-defined procedures probably minimized bias
      Woollard et al, 2003 64 NR No (weight loss), yes (lipid) 71% RER Fair
Outcome measurement by nurse giving intervention
Details of outcome measures NR
  Subclinical
      Parikh et al, 2010 (Project HEED) 49 NR NR 73% No Fair
Small number of participants
      HPT, 1990 28 Yes Likely 91% No Good
      DPP, 2005 85 Yes Partial 95% No Good
Outcomes assessment seems unblinded but required initial certification and annual recertification of assessment staff, which should minimize if not eliminate bias introduced by lack of blinding
      Stevens et al, 1993 (TOHP I) 54 Yes Yes 94% No Good
      Stevens et al, 2001 (TOHP II) 55 Yes Yes 92% No Good
      Villareal et al, 2008 59 Yes Yes 89% LOCF Fair
      Mensink et al, 2003 46 Unclear NR 81% No Fair
      Tuomilehto et al, 2001 58 Unclear NR 97% No Good
Uncertain if allocation concealed; person scheduling baseline appointments was blinded to randomization list, but there is uncertainty whether this was the person who conducted the assessment
      Kulzer et al, 2009 42 NR NR 91% BOCF Fair
Group-specific follow-up NR
      Mitsui et al, 2008 23 NR NR 94% No Fair
Small number of participants, higher proportion of control group had the metabolic syndrome than intervention group (32% vs. 21%)
 Low risk or unselected
      Cussler et al, 2008 33 NR NR 82% BOCF Fair
Did not adjust analysis for cluster randomization
      Fitzgibbon et al, 2010 (ORBIT) 35 Yes No 89% Mlmp Fair
Assessment not blinded, but well-defined procedures probably minimized bias
      Haapala et al, 2009 37 Yes NR 68% BOCF or LOCF value that was highest Fair
      Irwin et al, 2003 (PATH) 38 Yes Yes 98% BOCF Good
      Jeffery et al, 1993 39 NR NR 87% No Fair
Measurement procedures not well described, attrition by group NR
      Martin et al, 2008 44 NR NR 65% LOCF Fair
Group-specific attrition not provided at 12 mo, retention was lower in intervention group than control group at 6-mo (71% vs. 88%) and 18-mo (54% vs. 77%) follow-up
      Moore et al, 2003 47 Yes Yes 67% No Fair
      Narayan et al, 1998 48 NR NR 93% NR Fair
BMI, weight, waist circumference, and fasting glucose levels higher in intervention group at baseline; measurement procedures not clearly described.
      Perri et al, 1988 50 NR NR 74% No Fair
Little information about baseline comparability
      Pritchard et al, 1999 51 Likely NR 66% No Fair
Lower retention in dietitian group than other 2 groups (54.5% vs. 71% and 71%); outcomes reported only for overweight/obesity, hypertension, and DM subgroups, although randomization was not stratified by disease status; statistical procedures not well-described
      Silva et al, 2010 52 NR NR 81% BOCF Fair
Lower retention in control group than intervention group 80% vs. 93%; lack of information about blinding of assessment and blinding, but well-defined procedures probably minimized bias
      Simkin-Silverman et al, 2003 (WHLP) 53 Yes Yes 94% No Good
      Werkman et al, 2010 60 No NR 95% No Fair
Did not have blinded outcomes assessment, but well-defined procedures probably minimized bias; analyzed only male participants (so not truly randomized comparison)
      Wood et al, 1991 63 NR NR 88% No Fair
      Wood et al, 1988 62 Yes NR 85% No Fair
Retention higher in exercise than other groups (90% vs. 81% and 82%)
Medication trials
  Orlistat
      Berne et al, 2005 65 NR Yes 86% LOCF Fair
Possible selective reporting of weight outcomes
      Broom et al, 2002 66 NR Yes 65% LOCF Fair
Statistical procedures not well described
      Davidson et al, 1999 67 NR Yes 66% LOCF Fair
High dropout during run-in
      Derosa et al, 2003 68 Yes Yes 96% No Fair
Small sample, measurement methods not clearly described
      Derosa et al, 2010 69 Yes Yes 92% NR Good
      Finer et al, 2000 70 Yes Yes 61% LOCF Fair
      Hanefeld and Sachse, 2002 71 NR Yes 69% LOCF Fair
Measurement procedures not well described
      Hauptman et al, 2000 72 NR Yes 67% LOCF Fair
      Hill et al, 1999 73 NR Yes 74% LOCF Fair
Measurement procedures not well described
Did not report whether placebo matched active medicine
      Hollander et al, 1998 74 NR Yes 79% Unclear Fair
      Krempf et al, 2003 75 NR Yes 61% No Fair
      Lindgärde, 2000 76 NR Yes 86% NR Fair
      Miles et al, 2002 77 NR Yes 60% LOCF Fair
Did not report whether placebo matched active medicine
      Richelsen et al, 2007 78 Yes Yes 65% LOCF Fair
      Rössner et al, 2000 79 NR Yes 72% LOCF Fair
      Sjöström et al, 1998 80 Likely Yes 79% LOCF Fair
      Swinburn et al, 2005 81 NR Yes 79% LOCF Fair
Did not report whether placebo matched active medicine
      Torgerson et al, 2004 (XENDOS)82 Yes Yes 83% LOCF Fair
Higher retention in control than intervention group (90% vs. 78%)
  Metformin
       Fontbonne et al, 1996 (BIGPRO)22 NR Yes 71% LOCF Fair
      Gambineri et al, 200683 NR NR 98% No Fair
Not double blind—only participants blinded
      DPP, 200585 Yes Partial 95% No Good
Nonlaboratory outcomes assessment seems unblinded but required initial certification and annual recertification of assessment staff, which should minimize if not eliminate bias introduced by lack of blinding

ADAPT = Activity, Diet and Blood Pressure Trial; BIGPRO = BIGuanides and Prevention of the Risks in Obesity; BMI = body mass index; BOA = blinding of outcomes assessment; BOCF = baseline-observation-carried-forward method; CV = cardiovascular; DM = diabetes mellitus; DISH = Dietary Intervention to Study Hypertension; DPP = Diabetes Prevention Program; HEED = Help Educate to Eliminate Diabetes; HOT = Hypertension Optimal Treatment; HPT = Hypertension Prevention Trial; ITT = intention-to-treat; LIHEF = Lifestyle Intervention against Hypertension in Eastern Finland; LOCF = last-observation-carried-forward method; MImp = multiple imputation method; NA = not applicable; NR = not reported; ODES = Oslo Diet and Exercise Study; ORBIT = Obesity Reduction Black Intervention Trial; PATH = Physical Activity for Total Health; RER = imputation of missing data through use of random-effects regression; TAIM = Trial of Antihypertensive Interventions and Management; TOHP = Trials of Hypertension Prevention; TONE = Trial of Nonpharmacologic Interventions in the Elderly; WHLP = Women's Healthy Lifestyle Project; WLM = Weight Loss Maintenance; X = outcome was reported; XENDOS = XENical in the Prevention of Diabetes in Obese Subjects; XX = outcome was included in the meta-analysis.
* Proportion with follow-up data.

Current as of: October 2011

Internet Citation: Final Evidence Summary: Obesity in Adults: Screening and Management. U.S. Preventive Services Task Force. October 2011.
https://www.uspreventiveservicestaskforce.org/Page/Document/final-evidence-summary38/obesity-in-adults-screening-and-management

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