Weight Loss to Prevent Obesity-Related Morbidity and Mortality in Adults: Behavioral Interventions
September 18, 2018
Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.
By Erin S. LeBlanc, MD, MPH; Carrie D. Patnode, PhD, MPH; Elizabeth M. Webber, MS; Nadia Redmond, MSPH; Megan Rushkin, MPH; and Elizabeth A. O’Connor, PhD
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 published in JAMA on September 18, 2018.
Importance: Overweight and obesity have been associated with adverse health effects.
Objective: To systematically review evidence on benefits and harms of behavioral and pharmacotherapy weight loss and weight loss maintenance interventions in adults to inform the US Preventive Services Task Force.
Data Sources: MEDLINE, PubMed Publisher-Supplied Records, PsycINFO, and the Cochrane Central Register of Controlled Trials for studies published through June 6, 2017; ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials through August 2017; and ongoing surveillance in targeted publications through March 23, 2018. Studies from previous reviews were re-evaluated for inclusion.
Study Selection: Randomized clinical trials (RCTs) focusing on weight loss or weight loss maintenance in adults.
Data Extraction and Synthesis: Data were abstracted by one reviewer and confirmed by another. Random-effects meta-analyses were conducted for weight loss outcomes in behavior-based interventions.
Main Outcomes and Measures: Health outcomes, weight loss or weight loss maintenance, reduction in obesity-related conditions, and adverse events.
Results: A total of 122 RCTs (N = 62,533) and 2 observational studies (N = 209,993) were identified. Compared with controls, participants in behavior-based interventions had greater mean weight loss at 12 to 18 months (−2.39 kg [95% CI, −2.86 to −1.93]; 67 studies [n = 22,065]) and less weight regain (−1.59 kg [95% CI, −2.38 to −0.79]; 8 studies [n = 1408]). Studies of medication-based weight loss and maintenance interventions also reported greater weight loss or less weight regain in intervention compared with placebo groups at 12 to 18 months (range, −0.6 to −5.8 kg; no meta-analysis). Participants with prediabetes in weight loss interventions had a lower risk of developing diabetes compared with controls (relative risk, 0.67 [95% CI, 0.51 to 0.89]). There was no evidence of other benefits, but most health outcomes such as mortality, cardiovascular disease, and cancer were infrequently reported. Small improvements in quality of life in some medication trials were noted but were of unclear clinical significance. There was no evidence of harm such as cardiovascular disease from behavior-based interventions; higher rates of adverse events were associated with higher dropout rates in medication groups than in placebo groups.
Conclusions and Relevance: Behavior-based weight loss interventions with or without weight loss medications were associated with more weight loss and a lower risk of developing diabetes than control conditions. Weight loss medications, but not behavior-based interventions, were associated with higher rates of harms. Long-term weight and health outcomes data, as well as data on important subgroups, were limited.
Between 2011 and 2014, 73.0% of US men and 66.2% of US women were overweight or had obesity,1 which are associated with multiple negative health effects.2-7 Although measuring weight at periodic health examinations is now part of standard clinical practice in most medical settings, rates of consistently and systematically documenting obesity and tracking weight over time are low,8,9 as are rates of primary care–delivered, weight-related counseling.8,10-14
In 2012, the US Preventive Services Task Force (USPSTF) recommended that clinicians screen all adults for obesity and offer or refer patients with body mass index (BMI) of 30 or higher (calculated as weight in kilograms divided by height in meters squared) to intensive, multicomponent behavioral interventions (B recommendation).15 This review was undertaken to provide current evidence to the USPTF for an updated recommendation on this topic.
Scope of Review
This review addressed 3 key questions (KQs) (Figure 1). Full methodological details (including study selection, excluded studies, and description of data analyses) are publicly available in the full evidence report at https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/obesity-in-adults-interventions1.
Data Sources and Searches
In addition to considering all studies from the previous review on this topic,17 a comprehensive search of MEDLINE, PubMed Publisher-Supplied Records, PsycINFO, and the Cochrane Central Register of Controlled Trials was performed. The search was between January 1, 2010, and June 6, 2017, building on the most recent full search for this topic. We worked with a research librarian to develop the search strategy, which was peer-reviewed by a second research librarian. All searches were limited to articles published in English.
In addition to these database searches, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (http://www.who.int/ictrp) were searched for ongoing trials through August 2017. The reference lists of previously published reviews, meta-analyses, and primary studies were also examined to identify any potential studies for inclusion. The US Food and Drug Administration (FDA) review documents for each included medication were examined to identify any additional studies not published in the primary literature. The searches were supplemented with suggestions from experts and articles identified through news and table-of-contents alerts such as those produced by the USPSTF Scientific Resource Center LitWatch activity.16 Since June 2017, ongoing surveillance through article alerts and targeted searches of journals with a high impact factor and journals relevant to the topic was conducted to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and therefore the related USPSTF recommendation. The last surveillance was conducted on March 23, 2018, and identified no additional studies.
Two reviewers independently reviewed all identified titles and abstracts and relevant full-text articles against a priori inclusion and exclusion criteria for design, population, intervention, and outcomes. Disagreements in the abstract and full-text review were resolved by discussion. Eligible studies included fair- and good-quality randomized clinical trials (RCTs) of primary care–relevant weight loss or weight loss maintenance interventions (behavioral counseling [either alone or part of a multicomponent intervention], training of clinicians, and pharmacologic interventions approved by the FDA as first-line long-term weight loss or weight loss maintenance medications [orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide]). Weight outcomes at least 12 months after intervention start were required. For harms, RCTs, systematic reviews, and large cohort, case-control, or event-monitoring studies were allowed; there was no minimum follow-up.
Studies were required to focus on weight loss in adults 18 years or older who were candidates for weight loss or weight loss maintenance interventions and selected based on an above-normal BMI (eg, ≥25) or other weight-related measure (eg, waist circumference). In cases in which lower BMI thresholds were used for eligibility (eg, ≥23) or in which participants were selected based on other cardiovascular risk factors without weight-related eligibility criteria and the focus of the intervention was clearly weight loss, the distribution of the mean BMI at baseline was examined to evaluate potential inclusion. Studies were included in which 100% of the sample had a BMI above 23, 95% of the sample had a BMI above 24, or 90% of the sample had a BMI above 25. Individuals may have had additional cardiovascular risk factors (eg, hypertension); however, studies of adults with a chronic disease for which weight loss or weight loss maintenance is part of disease management (eg, known cardiovascular disease, diabetes mellitus) were excluded. In addition, studies in adults with known chronic diseases not generalizable to the primary care population (eg, eating disorders, chronic kidney disease) were excluded. Studies in adults with secondary causes of obesity, in pregnant women, and in institutionalized adults were excluded.
For studies of behavior-based interventions, it was required that controls have no intervention (eg, wait list, usual care, assessment only), minimal intervention (eg, usual care limited to quarterly counseling sessions or generic brochures), or be attention controls (eg, similar format and intensity but different content). For studies of pharmacologic interventions, only placebo-controlled studies in which participants all received the same behavior-based interventions were included. Studies had to report a health outcome (mortality, morbidity, depression, health-related quality of life, and disability), intermediate outcomes (weight measurements, measures of total and central adiposity, incidence or prevalence of obesity-related conditions, and proportion of individuals taking medication for obesity-related conditions), or adverse events (treatment-related harms and discontinuation of medication because of adverse effects at any point during intervention).
Data Extraction and Quality Assessment
Two investigators independently assessed the methodological quality of each study using predefined study design–specific criteria developed by the USPSTF.16 Disagreements in quality were resolved by discussion. Each study was given a final quality rating of good, fair, or poor. Studies were excluded as poor quality if there were several important major risks of biases, including high attrition (generally >40%) or differential attrition between groups (generally >20%), lack of baseline comparability between groups without adjustment, methods for ascertainment of weight outcomes that were unclear or that differed between groups, or issues in trial conduct, analysis, or reporting of results that could invalidate results. Because this review was an update, critical appraisal of the original studies was not repeated, but the quality rating was confirmed during data abstraction. One reviewer extracted key elements and a second reviewer checked the data for accuracy. For each study, general characteristics of the study, clinical and demographic characteristics of the sample and setting, analytic methods, and results were extracted. This included both absolute weight change and percentage of participants who achieved 5% loss of their baseline weight, which is considered by the FDA to be clinically meaningful and a primary weight loss outcome.18
Data Synthesis and Analysis
Summary tables of study, population, and intervention characteristics, as well as outcomes for each KQ, were created according to the focus of the intervention (ie, behavior-based weight loss interventions, behavior-based weight loss maintenance interventions, medication-based weight loss interventions, and medication-based weight loss maintenance interventions). The data on health outcomes (KQ1) and adverse events (KQ3) did not allow for quantitative pooling because of the limited number of contributing studies and the variability in outcomes measured.
Details of the data analysis methods are included in the full report. For weight outcomes in behavior-based interventions, random-effects meta-analyses were conducted using the method of DerSimonian and Laird to calculate the pooled differences in mean changes (for continuous data) and a pooled risk ratio (for binary data) for weight outcomes (KQ2).19 Statistical heterogeneity among the pooled studies was examined using standard χ2 tests, and the proportion of total variability in point estimates was estimated using the I2 statistic.20 Funnel plots were generated to evaluate small-study effects (a possible indication of publication bias) and the Egger21 or Peters22 tests were used to assess the statistical significance of imbalance in study size as well as findings that suggested a pattern. Data from medication trials could not be pooled because of the small number of studies for each medication or variability in reporting between trials.
A series of meta-regression analyses were conducted to investigate whether variability among the results was associated with any prespecified study, population, or intervention characteristics. Specifically, we examined study quality (good vs fair), percentage of participants retained at 12 to 18 months, link to primary care (conducted in or recruited from primary care), whether the trial was set in the United States, risk status of the sample (increased cardiovascular risk [eg, hypertension], subclinical cardiovascular risk [eg, impaired fasting glucose], or cancer risk vs low risk or unselected), participant selection approach (self-selected vs directly recruited), and several intervention characteristics (number of sessions and contacts in the first year; intervention duration; main mode of intervention delivery; presence of any group, individual, or technology-based components; and use of self-monitoring).
Quantitative analyses were conducted using Stata version 13.1 (Stata Corp LP). All significance testing was 2-sided, and results were considered statistically significant if the P value was 0.05 or less.
A total of 15,483 titles and abstracts and 572 articles were reviewed to determine if they met inclusion criteria, and 124 trials reported in 238 publications, including 122 RCTs (N = 62,533) and 2 observational studies (N = 209,993), were included (Figure 2).23-147 Forty-one studies were carried over from the prior review and were synthesized with 83 newly identified studies. Eighty-nine trials examined the effectiveness of behavior-based weight loss and weight loss maintenance interventions,24,25,27,29,32,34-36,39-44, 46, 47, 49, 53, 55, 56, 58, 62-71, 73,75,76,78-81,83-86,88-98,100,102-105,107-110,115-118,121, 122,124-127,130-147 and 35 examined the effectiveness or harms of medication for weight loss and weight loss maintenance.23,26,28,30,31,33,37, 38, 45, 48, 50-52, 54, 57, 59-61, 72, 74, 77, 82,87, 99, 101, 106, 111-114,119,120,123,128,129
Within the 89 behavior-based weight loss and weight loss maintenance trials, 120 unique weight loss interventions were evaluated. Although interventions were highly variable, specific weight loss messages and behavior change techniques were consistent across the trials. To better summarize the interventions, each intervention group was categorized according to the main mode of intervention delivery into the following groups: (1) group (41 groups in 28 trials), (2) individual (37 groups in 33 trials), (3) mixed (18 groups in 16 trials), (4) technology-based (22 groups in 20 trials), and (5) print-based (2 groups in 1 trial). The comparison groups in these trials included (1) minimal intervention (44 trials), (2) usual care (25 trials), (3) no intervention (9 trials), (4) wait list (7 trials), and (5) attention control (4 trials). Medication-based weight loss and weight loss maintenance studies examined FDA-approved dosages of medications: liraglutide (1.8 mg or 3.0 mg daily), lorcaserin (20 mg [10 mg twice daily]), naltrexone and bupropion (32/360 mg [16/180 mg 3 times daily]), orlistat (prescription strength dosage of 360 mg daily [120 mg 3 times daily] and over-the-counter dosage of 180 mg [60 mg 3 times daily]), and phentermine-topiramate (15/92 mg and 7.5/46 mg). Medication and placebo groups both received identical behavioral interventions.
Benefits for Health Outcomes
Key Question 1. Do primary care–relevant behavioral and/or pharmacotherapy weight loss and weight loss maintenance interventions lead to improved health outcomes among adults who are overweight or have obesity and are a candidate for weight loss interventions?
Health outcomes were infrequently reported in the behavior-based weight loss and maintenance trials (20 trials [n = 9910]). In 4 weight loss trials (n = 4442) reporting mortality, there were no significant differences between groups over 2 to 16 years.73,116,122,143,148-150 Two weight loss trials (n = 2666) reported on cardiovascular events, with neither trial finding significant differences between groups over 3 and 10 years.73,122,149,151 Health-related quality of life (QOL) was evaluated in 17 weight loss and maintenance trials (n = 7120), with 14 showing no differences between groups on any measure; in the 3 trials that noted statistically significant findings, the differences were only for some QOL components and were of unclear clinical significance (Table 1).29,46,47,56,62,65,73,76,89,92,96,102,110,126,127,132,140
Trials of medications for weight loss examined few health outcomes beyond QOL (10 trials [n = 13,145]).28,31,51,54,57,99,106,113,119,128 Although there was evidence of greater improvement on an obesity-specific QOL scale in participants randomized to receive medications for weight loss compared with placebo within most of the trials, the differences were small and of unclear clinical significance, especially given high dropout rates in medication trials. None of the medication-based maintenance trials reported the effects of the interventions on health outcomes.
Benefits for Weight Control
Key Question 2. Do primary care–relevant behavioral and/or pharmacotherapy weight loss and weight loss maintenance interventions lead to weight loss, weight loss maintenance, or a reduction in the incidence or prevalence of obesity-related conditions among adults who are overweight or have obesity and are a candidate for weight loss interventions?
Participants who received behavior-based weight loss interventions generally lost more weight and had greater reductions in waist circumference than those in control conditions at up to 24 months of follow-up. Intervention participants had a pooled −2.4 kg (−5.3 lb) (95% CI, −2.8 to −1.9 kg; 67 trials [n = 22,065]; I2 = 90.0%) greater weight loss at 12 to 18 months (Figure 3). Mean absolute changes in weight ranged from −0.5 kg (−1.1 lb) to −9.3 kg (−20.5 lb) among intervention participants and from 1.4 kg (3.0 lb) to −5.6 (−12.3 lb) among control participants. In addition, intervention participants were more likely to achieve 5% weight loss from baseline compared with control participants (pooled risk ratio, 1.94 [95% CI, 1.70 to 2.22]; 38 trials [n = 12,231]; I2 = 67.2%), which translated into a number needed to treat of 8. Heterogeneity in the interventions, confounded with differences in the populations, settings, and trial quality, made it difficult to identify which variables (ie, number of sessions, in-person vs remote sessions, group- vs individual-based) may be driving larger effects. Although weight outcomes were less well reported beyond 12 months, weight loss remained significantly greater in intervention compared with control conditions in interventions lasting up to 36 months. Participants who received behavior-based weight loss maintenance interventions generally maintained more of their weight loss compared with those in control conditions (pooled mean difference, −1.6 kg [−3.5 lb] [95% CI, −2.4 to −0.8 kg]; 8 trials [n = 1408]; I2 = 26.8%) in the intervention vs control groups.
In the 2 largest and longest good-quality trials (n = 1818), participants randomized to behavior-based weight loss interventions had a decreased probability of developing type 2 diabetes compared with control conditions, with an absolute risk reduction of approximately 14.5% in both trials over 3 to 9 years.73,122,159 Although 11 smaller and generally shorter-duration weight loss trials did not find significant differences between groups, when pooled with the larger trials, there was a significant reduction in risk of developing diabetes over 1 to 9 years (pooled risk ratio, 0.67 [95% CI, 0.51 to 0.89]; 9 trials [n = 3140]; I2 = 49.2%) (Figure 4). Across all 13 of these trials, almost all were limited to adults with impaired fasting glucose. Three large trials (n = 3916) noted benefits of behavior-based weight loss on hypertension and hyperlipidemia diagnosis, medication use, or both116,148,151; however, effects were not found in 5 smaller trials.43,66,102,105,144 Effects on the metabolic syndrome56,73,79,100,105 and cardiovascular disease risk score were mixed.24,56
Participants randomized to receive weight loss medications had more weight loss, were more likely to lose 5% of their weight, and experienced a greater decrease in waist circumference than those receiving placebo (Table 2). Participants who received medications to assist with weight loss maintenance generally maintained more of their weight loss and waist circumference decrease compared with those in control conditions. However, the results were limited by high dropout rates and relatively short follow-up duration in some trials. The most common intermediate outcome reported (4 studies [n = 9763]) was incident diabetes, and there was a decreased risk of developing diabetes over 1 to 4 years in participants given medications; however, these trials were similarly limited by high dropout rates. Other intermediate outcomes were sparsely reported and showed mixed results.
Harms of Interventions
Key Question 3. What are the adverse effects of primary care–relevant behavioral and/or pharmacotherapy weight loss and weight loss maintenance interventions in adults who are overweight or have obesity and are a candidate for weight loss interventions?
Rates of adverse events were infrequently reported in the behavior-based weight loss and weight loss maintenance trials (30 trials [n = 12,824]).25,27,29,35,36,47,49,55,62,64,66,71,73,78,80,92,96,103-105,110,121,125, 127,137,138,140,142,145,147 In general, there were no serious harms related to the interventions and most trials noted no differences between groups in the rates of adverse events, including cardiovascular events. In the 3 trials large enough to examine differences in musculoskeletal issues between groups, results were mixed.25,73,105
Almost all medication trials reported adverse events. Weight loss medications were associated with more adverse events than placebo, which was associated with higher dropout rates for adverse events in the medication groups than in the placebo groups. However, serious adverse events were not generally more common in participants randomized to medications. There are multiple potential harms required by the FDA to be listed on weight loss medication labels, but these harms have not been well evaluated in the trials included in this review.
The summary of evidence is shown in Table 3. Behavior-based weight loss interventions were associated with more weight loss, and behavior-based weight loss maintenance interventions were associated with less weight regain, than control conditions over 12 to 18 months. The degree of weight loss in the current review is slightly smaller but consistent in magnitude with the 2011 review on this topic. Although addressed in fewer trials, weight loss or weight loss maintenance interventions lasting up to 36 months reported significantly greater weight loss or weight loss maintenance in the intervention participants compared with control participants. Weight loss estimates were consistent and precise over time; however, pooled analyses showed considerable statistical heterogeneity, reflecting heterogeneity in intervention groups and differences in populations, settings, and designs. Using various modes of intervention delivery (group, individual, mixed, technology-based, and print-based), trials were generally designed to help participants achieve or maintain a 5% or greater weight loss through a combination of dietary changes and increased physical activity. As in the previous review, behavior-based weight loss interventions were associated with a decreased risk of progressing from prediabetes to type 2 diabetes at up to 36 months of follow-up. Other intermediate- and longer-term health outcomes were infrequently reported, and in those studies reporting such outcomes, most were underpowered. Adverse events of behavior-based interventions were sparsely reported, but no serious harms were related to interventions.
FDA-approved weight loss medications (liraglutide, lorcaserin, naltrexone and bupropion, orlistat, and phentermine-topiramate) were associated with more weight loss and weight loss maintenance and a decreased incidence of progression to type 2 diabetes compared with placebo at up to 48 months of follow-up. Although weight loss medication studies reported improvements on obesity-specific QOL measures, comparative scores were often missing, and differences were small and of unclear significance. Although rates of serious adverse events were low and generally similar between groups, participants randomized to medications experienced more adverse events, resulting in higher withdrawal rates, compared with those in the placebo groups. The medication evidence was limited by the small number of trials for each medication, methodological variability, missing data regarding dispersion, poor follow-up, and limited applicability (given that participants had to meet narrowly defined inclusion criteria).
Intentional weight loss among individuals who have obesity may lead to a small decrease in mortality risk, although the observational literature is conflicting, especially for men and for individuals without obesity-related comorbidities.161-163 The literature is limited on the effects of intentional weight loss on other outcomes (eg, cardiovascular disease and cancer).164,165 In the context of sparse direct trial evidence on health outcomes, observational evidence does not suggest that intentional weight loss among those who are overweight, especially those with BMIs less than 28, is associated with decreased mortality.166-170 Individuals who undergo bariatric surgery experience significant improvements in diabetes,171,172 sleep apnea,172,173 QOL,174 depression,175 and pain and physical function,176 although data on long-term health outcomes such as mortality, cardiovascular disease, and cancer are still lacking. The amount of weight loss that occurs with weight loss surgery, however, is much greater than what can usually be achieved with behavior-based weight loss interventions and there are metabolic changes that occur after surgery, independent of weight loss, that could contribute to improvements in health outcomes after surgery.177
This review had several limitations. First, tertiary prevention studies were excluded if they specifically focused on persons with conditions for which weight loss is considered as part of disease management (eg, diabetes, polycystic ovarian syndrome), and studies of surgery or nonsurgical devices were excluded because these studies were considered outside the scope of primary care–relevant interventions.
Second, the review did not include continuous intermediate outcomes (eg, continuous measures of blood pressure, cholesterol levels, glucose levels); rather, it focused on specific diseases or risk factors (eg, diabetes, hypertension).
Third, data were pooled across a body of literature that was heterogeneous with respect to demographic characteristics, interventions, and settings. The considerable statistical heterogeneity (I2 >85%) indicates that the pooled results should be interpreted with caution and confidence interval estimates should be primarily used to understand the magnitude of effects. Across the trials, there were large standard deviations relative to the mean change, suggesting that some adults showed fairly large reductions in weight, some showed no or modest changes, and some gained weight.
Fourth, given the heterogeneity among intervention groups and differences in populations and settings, it was not possible to identify if particular intervention variables (ie, number of sessions, in-person vs remote, group- vs individual-based) were more effective. To fully address this would require examination of comparative effectiveness studies (which were specifically excluded in this review). However, the consistency seen across specific interventions and across various subgroups (albeit with a wide range in effect sizes) suggests that benefits are likely dependent on individual, social, and environmental factors rather than specific intervention characteristics.
Fifth, although weight loss interventions (both behavior-based and medication-based) were associated with short-term weight loss, there remains a paucity of data on what happens long term. Only a limited number of trials reported follow-up beyond 24 months, and in most of those, ongoing weight loss or maintenance sessions, medication use, or both occurred throughout follow-up. Survey data suggest that a minority of individuals are successful at long-term weight loss maintenance.178,179
Sixth, there was also a paucity of data on long-term health outcomes. While it appears that weight loss interventions can reduce diabetes incidence, larger trials with longer-term follow-up are required to understand the full benefits of these interventions on health outcomes and whether those effects are long-lasting. Additionally, there were few data on patient-centered outcomes such as QOL and psychological outcomes such as weight stigmatization,180 eating disorders,181-183 and weight fluctuation (“yo-yo” dieting).184-186
Seventh, many of the trials, especially those examining weight loss medications, may have been biased by high attrition; nearly half of the studies had attrition of 35% or more. Studies with high attrition were included because early discontinuation was likely a result of the intervention (ie, adverse effects, lack of weight loss, time commitments) and not necessarily design flaws. Although it was required that trials use multiple imputation methods or procedures for accounting for missing data, imputing such large amounts of data might have led to biased comparisons in unknown directions.
Eighth, almost all studies relied on BMI to identify their populations. Although long-term health risks increase with increasing BMI, the precise BMI at which increased risk occurs—and the strength of the relationship—appears to vary by race/ethnicity, age, and personal or lifestyle factors.187-213 Participants generally fell into the overweight and obese categories, and results were not reliably stratified by BMI. It was therefore not possible to make conclusions about whether the health effects of weight loss interventions varied according to baseline BMI category, age, and race/ethnicity. Future trials should examine the effects of weight loss interventions in diverse populations stratified by BMI as well as emerging classification systems, which include assessment of physical, mental, and functional health to characterize obesity severity.214,215
Behavior-based weight loss interventions with or without weight loss medications were associated with more weight loss and a lower risk of developing diabetes than control conditions. Weight loss medications, but not behavior-based interventions, were associated with higher rates of harms. Long-term weight and health outcomes data, as well as data on important subgroups, were limited.
Source: This article was first published in the Journal of the American Medical Association on September 18, 2018 (JAMA. 2018;320(11):1172-1991).
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr LeBlanc reported that her institution received a grant from Merck Inc for a project (unrelated to the topic of this article) on which she served as principal investigator. No other disclosures were reported.
Funding/Support: This research was funded under contract HHSA290201200015I, Task Order 6, from the Agency for Healthcare Research and Quality (AHRQ), US Department of Health and Human Services, under a contract to support the USPSTF.
Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ had no role in study selection, quality assessment, or synthesis. AHRQ staff provided project oversight, reviewed the report to ensure that the analysis met methodological standards, and distributed the draft for peer review. Otherwise, AHRQ had no role in the conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript findings. The opinions expressed in this document are those of the authors and do not reflect the official position of AHRQ or the US Department of Health and Human Services.
Additional Information: A draft version of this evidence report underwent external peer review from 7 content experts (George A. Bray, MD, Louisiana State University; Stephanie Fitzpatrick, PhD, Kaiser Permanente; Katherine Flegal, PhD, Stanford University; James O. Hill, PhD, University of Colorado; F. Xavier Pi-Sunyer, MD, Columbia University; Nancy E. Sherwood, PhD, University of Minnesota; Thomas A. Wadden, PhD, University of Pennsylvania) and 4 federal partners (Centers for Disease Control and Prevention, Department of Veterans Affairs, National Cancer Institute, and National Institutes of Health). Comments from reviewers were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.
1. United States, Report 2016: With Chartbook on Long-term Trends in Health. Centers for Disease Control and Prevention website. https://www.cdc.gov/nchs/data/hus/hus16.pdf. 2017. Accessed May 23, 2017.
2. Bogers RP, Bemelmans WJ, Hoogenveen RT, et al; BMI-CHD Collaboration Investigators. Association of overweight with increased risk of coronary heart disease partly independent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300,000 persons. Arch Intern Med. 2007;167(16):1720-1728. doi:10.1001/archinte.167.16.1720
3. Colditz GA, Willett WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122(7):481-486. doi:10.7326/0003-4819-122-7-199504010-00001
4. Guh DP, Zhang W, Bansback N, Amarsi Z, Birmingham CL, Anis AH. The incidence of co-morbidities related to obesity and overweight: a systematic review and meta-analysis. BMC Public Health. 2009;9:88. doi:10.1186/1471-2458-9-88
5. Bhaskaran K, Douglas I, Forbes H, dos-Santos-Silva I, Leon DA, Smeeth L. Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5.24 million UK adults. Lancet. 2014;384(9945):755-765. doi:10.1016/S0140-6736(14)60892-8
6. Kyrgiou M, Kalliala I, Markozannes G, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017;356:j477. doi:10.1136/bmj.j477
7. Afshin A, Forouzanfar MH, Reitsma MB, et al; GBD 2015 Obesity Collaborators. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377(1):13-27. doi:10.1056/NEJMoa1614362
8. Smith AW, Borowski LA, Liu B, et al. U.S. primary care physicians’ diet-, physical activity-, and weight-related care of adult patients. Am J Prev Med. 2011;41(1):33-42. doi:10.1016/j.amepre.2011.03.017
9. Steeves JA, Liu B, Willis G, Lee R, Smith AW. Physicians’ personal beliefs about weight-related care and their associations with care delivery: the U.S. National Survey of Energy Balance Related Care Among Primary Care Physicians. Obes Res Clin Pract. 2015;9(3):243-255. doi:10.1016/j.orcp.2014.08.002
10. Kraschnewski JL, Sciamanna CN, Stuckey HL, et al. A silent response to the obesity epidemic: decline in US physician-weight counseling. Med Care. 2013;51(2):186-192. doi:10.1097/MLR.0b013e3182726c33
11. Ma J, Xiao L, Yank V. Variations between obese Latinos and whites in weight-related counseling during preventive clinical visits in the United States. Obesity (Silver Spring). 2013;21(8):1734-1741. doi:10.1002/oby.20285
12. Ma J, Xiao L, Stafford RS. Underdiagnosis of obesity in adults in US outpatient settings. Arch Intern Med. 2009;169(3):313-314. doi:10.1001/archinternmed.2008.582
13. Simkin-Silverman LR, Gleason KA, King WC, et al. Predictors of weight control advice in primary care practices: patient health and psychosocial characteristics. Prev Med. 2005;40(1):71-82. doi:10.1016/j.ypmed.2004.05.012
14. Stafford RS, Farhat JH, Misra B, Schoenfeld DA. National patterns of physician activities related to obesity management. Arch Fam Med. 2000;9(7):631-638. doi:10.1001/archfami.9.7.631
15. U.S. Preventive Services Task Force. Screening for and management of obesity in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157(5):373-378.
16. U.S. Preventive Services Task Force. U.S. Preventive Services Task Force Procedure Manual. Rockville, MD: U.S. Preventive Services Task Force; 2015.
17. LeBlanc E, O’Connor E, Whitlock EP, Patnode C, Kapka T. Screening for and Management of Obesity and Overweight in Adults. Rockville, MD: Agency for Healthcare Research and Quality; 2011. Evidence synthesis 89.
18. Guidance for Industry: Developing Products for Weight Management: Draft Guidance. US Food and Drug Administration website. https://www.fda.gov/downloads/Drugs/Guidances/ucm071612.pdf. Published February 2007. Accessed June 22, 2018.
19. DerSimonian R, Laird N. Meta-analysis in clinical trials. Am J Clin Nutr. 1986;7(3):177-188. doi:10.1016/0197-2456(86)90046-2
20. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-1558. doi:10.1002/sim.1186
21. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-634. doi:10.1136/bmj.315.7109.629
22. Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L. Comparison of two methods to detect publication bias in meta-analysis. JAMA. 2006;295(6):676-680. doi:10.1001/jama.295.6.676
23. Acharya NV, Wilton LV, Shakir SA. Safety profile of orlistat: results of a prescription-event monitoring study. Int J Obes (Lond). 2006;30(11):1645-1652. doi:10.1038/sj.ijo.0803323
24. Ackermann RT, Finch EA, Brizendine E, Zhou H, Marrero DG. Translating the diabetes prevention program into the community: the DEPLOY pilot study. Am J Prev Med. 2008;35(4):357-363. doi:10.1016/j.amepre.2008.06.035
25. Ackermann RT, Liss DT, Finch EA, et al. A randomized comparative effectiveness trial for preventing type 2 diabetes. Am J Public Health. 2015;105(11):2328-2334. doi:10.2105/AJPH.2015.302641
26. Allison DB, Gadde KM, Garvey WT, et al. Controlled-release phentermine/topiramate in severely obese adults: a randomized controlled trial (EQUIP). Obesity (Silver Spring). 2012;20(2):330-342. doi:10.1038/oby.2011.330
27. Anderson AS, Craigie AM, Caswell S, et al. The impact of a bodyweight and physical activity intervention (BeWEL) initiated through a national colorectal cancer screening programme: randomised controlled trial. BMJ. 2014;348:g1823. doi:10.1136/bmj.g1823
28. Apovian CM, Aronne L, Rubino D, et al; COR-II Study Group. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity (Silver Spring). 2013;21(5):935-943. doi:10.1002/oby.20309
29. Appel LJ, Clark JM, Yeh HC, et al. Comparative effectiveness of weight-loss interventions in clinical practice. N Engl J Med. 2011;365(21):1959-1968. doi:10.1056/NEJMoa1108660
30. Aronne LJ, Wadden TA, Peterson C, Winslow D, Odeh S, Gadde KM. Evaluation of phentermine and topiramate versus phentermine/topiramate extended-release in obese adults. Obesity (Silver Spring). 2013;21(11):2163-2171. doi:10.1002/oby.20584
31. Astrup A, Carraro R, Finer N, et al; NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obes (Lond). 2012;36(6):843-854. doi:10.1038/ijo.2011.158
32. Aveyard P, Lewis A, Tearne S, et al. Screening and brief intervention for obesity in primary care: a parallel, two-arm, randomised trial. Lancet. 2016;388(10059):2492-2500. doi:10.1016/S0140-6736(16)31893-1
33. Bakris G, Calhoun D, Egan B, Hellmann C, Dolker M, Kingma I; Orlistat and Resistant Hypertension Investigators. Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens. 2002;20(11):2257-2267. doi:10.1097/00004872-200211000-00026
34. Befort CA, Klemp JR, Sullivan DK, et al.Weight loss maintenance strategies among rural breast cancer survivors: the rural women connecting for better health trial. Obesity (Silver Spring). 2016;24(10):2070-2077. doi:10.1002/oby.21625
35. Bennett GG, Warner ET, Glasgow RE, et al; Be Fit, Be Well Study Investigators. Obesity treatment for socioeconomically disadvantaged patients in primary care practice. Arch Intern Med. 2012;172(7):565-574. doi:10.1001/archinternmed.2012.1
36. Bhopal RS, Douglas A, Wallia S, et al. Effect of a lifestyle intervention on weight change in South Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trial. Lancet Diabetes Endocrinol. 2014;2(3):218-227. doi:10.1016/S2213-8587(13)70204-3
37. Broom I, Hughes E, Dodson P, Reckless J. The role of orlistat in the treatment of obese patients with mild to moderate hypercholesterolaemia: consequences for coronary risk. Br J Cardiol. 2002;9(8):460-468.
38. Broom I, Wilding J, Stott P, Myers N; UK Multimorbidity Study Group. Randomised trial of the effect of orlistat on body weight and cardiovascular disease risk profile in obese patients: UK Multimorbidity Study. Int J Clin Pract. 2002;56(7):494-499.
39. Burke V, Beilin LJ, Cutt HE, Mansour J, Wilson A, Mori TA. Effects of a lifestyle programme on ambulatory blood pressure and drug dosage in treated hypertensive patients: a randomized controlled trial. J Hypertens. 2005;23(6):1241-1249. doi:10.1097/01.hjh.0000170388.61579.4f
40. Cadmus-Bertram L, Nelson SH, Hartman S, Patterson RE, Parker BA, Pierce JP. Randomized trial of a phone- and web-based weight loss program for women at elevated breast cancer risk: the HELP study. J Behav Med. 2016;39(4):551-559. doi:10.1007/s10865-016-9735-9
41. Chirinos DA, Goldberg RB, Llabre MM, et al. Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial. J Behav Med. 2016;39(3):483-492. doi:10.1007/s10865-016-9721-2
42. Christian JG, Byers TE, Christian KK, et al. A computer support program that helps clinicians provide patients with metabolic syndrome tailored counseling to promote weight loss. J Am Diet Assoc. 2011;111(1):75-83. doi:10.1016/j.jada.2010.10.006
43. Cohen MD, D’Amico FJ, Merenstein JH. Weight reduction in obese hypertensive patients. Fam Med. 1991;23(1):25-28.
44. Cussler EC, Teixeira PJ, Going SB, et al. Maintenance of weight loss in overweight middle-aged women through the Internet. Obesity (Silver Spring). 2008;16(5):1052-1060. doi:10.1038/oby.2008.19
45. Davidson MH, Hauptman J, DiGirolamo M, et al. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial. JAMA. 1999;281(3):235-242. doi:10.1001/jama.281.3.235
46. de Vos BC, Runhaar J, Bierma-Zeinstra SM. Effectiveness of a tailor-made weight loss intervention in primary care. Eur J Nutr. 2014;53(1):95-104. doi:10.1007/s00394-013-0505-y
47. Demark-Wahnefried W, Jones LW, Snyder DC, et al. Daughters and Mothers Against Breast Cancer (DAMES): main outcomes of a randomized controlled trial of weight loss in overweight mothers with breast cancer and their overweight daughters. Cancer. 2014;120(16):2522-2534. doi:10.1002/cncr.28761
48. Derosa G, Mugellini A, Ciccarelli L, Fogari R. Randomized, double-blind, placebo-controlled comparison of the action of orlistat, fluvastatin, or both on anthropometric measurements, blood pressure, and lipid profile in obese patients with hypercholesterolemia prescribed a standardized diet. Clin Ther. 2003;25(4):1107-1122. doi:10.1016/S0149-2918(03)80070-X
49. Eaton CB, Hartman SJ, Perzanowski E, et al. A randomized clinical trial of a tailored lifestyle intervention for obese, sedentary, primary care patients. Ann Fam Med. 2016;14(4):311-319. doi:10.1370/afm.1952
50. Farr OM, Upadhyay J, Gavrieli A, et al. Lorcaserin administration decreases activation of brain centers in response to food cues and these emotion- and salience-related changes correlate with weight loss effects: a 4-week-long randomized, placebo-controlled, double-blind clinical trial. Diabetes. 2016;65(10):2943-2953. doi:10.2337/db16-0635
51. Fidler MC, Sanchez M, Raether B, et al; BLOSSOM Clinical Trial Group. A one-year randomized trial of lorcaserin for weight loss in obese and overweight adults: the BLOSSOM trial. J Clin Endocrinol Metab. 2011;96(10):3067-3077. doi:10.1210/jc.2011-1256
52. Finer N, James WP, Kopelman PG, Lean ME, Williams G. One-year treatment of obesity: a randomized, double-blind, placebo-controlled, multicentre study of orlistat, a gastrointestinal lipase inhibitor. Int J Obes Relat Metab Disord. 2000;24(3):306-313. doi:10.1038/sj.ijo.0801128
53. Fitzgibbon ML, Stolley MR, Schiffer L, Sharp LK, Singh V, Dyer A. Obesity Reduction Black Intervention Trial (ORBIT): 18-month results. Obesity (Silver Spring). 2010;18(12):2317-2325. doi:10.1038/oby.2010.47
54. Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial [published correction appears in Lancet. 2011;377(9776):1494]. Lancet. 2011;377(9774):1341-1352. doi:10.1016/S0140-6736(11)60205-5
55. Godino JG, Merchant G, Norman GJ, et al. Using social and mobile tools for weight loss in overweight and obese young adults (Project SMART): a 2 year, parallel-group, randomised, controlled trial. Lancet Diabetes Endocrinol. 2016;4(9):747-755. doi:10.1016/S2213-8587(16)30105-X
56. Greaves C, Gillison F, Stathi A, et al. Waste the waist: a pilot randomised controlled trial of a primary care based intervention to support lifestyle change in people with high cardiovascular risk. Int J Behav Nutr Phys Act. 2015;12:1. doi:10.1186/s12966-014-0159-z
57. Greenway FL, Fujioka K, Plodkowski RA, et al; COR-I Study Group. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [published corrections appear in Lancet. 2010;376(9750):1392 and 2010;376(9741):594]. Lancet. 2010;376(9741):595-605. doi:10.1016/S0140-6736(10)60888-4
58. Haapala I, Barengo NC, Biggs S, Surakka L, Manninen P. Weight loss by mobile phone: a 1-year effectiveness study. Public Health Nutr. 2009;12(12):2382-2391. doi:10.1017/S1368980009005230
59. Hauptman J, Lucas C, Boldrin MN, Collins H, Segal KR. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000;9(2):160-167. doi:10.1001/archfami.9.2.160
60. Hill JO, Hauptman J, Anderson JW, et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am J Clin Nutr. 1999;69(6):1108-1116. doi:10.1093/ajcn/69.6.1108
61. Hong JL, Meier CR, Sandler RS, Jick SS, Stürmer T. Risk of colorectal cancer after initiation of orlistat: matched cohort study. BMJ. 2013;347:f5039. doi:10.1136/bmj.f5039
62. Hunt K, Wyke S, Gray CM, et al. A gender-sensitised weight loss and healthy living programme for overweight and obese men delivered by Scottish Premier League football clubs (FFIT): a pragmatic randomised controlled trial. Lancet. 2014;383(9924):1211-1221. doi:10.1016/S0140-6736(13)62420-4
63. Huseinovic E, Bertz F, Leu Agelii M, Hellebö Johansson E, Winkvist A, Brekke HK. Effectiveness of a weight loss intervention in postpartum women: results from a randomized controlled trial in primary health care. Am J Clin Nutr. 2016;104(2):362-370. doi:10.3945/ajcn.116.135673
64. Jakicic JM, Otto AD, Lang W, et al. The effect of physical activity on 18-month weight change in overweight adults. Obesity (Silver Spring). 2011;19(1):100-109. doi:10.1038/oby.2010.122
65. Jansson SP, Engfeldt P, Magnuson A, Pt GL, Liljegren G. Interventions for lifestyle changes to promote weight reduction, a randomized controlled trial in primary health care. BMC Res Notes. 2013;6:213. doi:10.1186/1756-0500-6-213
66. Jebb SA, Ahern AL, Olson AD, et al. Primary care referral to a commercial provider for weight loss treatment versus standard care: a randomised controlled trial. Lancet. 2011;378(9801):1485-1492. doi:10.1016/S0140-6736(11)61344-5
67. Jeffery RW, Wing RR, Thorson C, et al. Strengthening behavioral interventions for weight loss: a randomized trial of food provision and monetary incentives. J Consult Clin Psychol. 1993;61(6):1038-1045. doi:10.1037/0022-006X.61.6.1038
68. Jolly K, Lewis A, Beach J, et al. Comparison of range of commercial or primary care led weight reduction programmes with minimal intervention control for weight loss in obesity: Lighten Up randomised controlled trial. BMJ. 2011;343:d6500. doi:10.1136/bmj.d6500
69. Jones DW, Miller ME, Wofford MR, et al. The effect of weight loss intervention on antihypertensive medication requirements in the Hypertension Optimal Treatment (HOT) study. Am J Hypertens. 1999;12(12, pt 1-2):1175-1180. doi:10.1016/S0895-7061(99)00123-5
70. Kanke S, Kawai T, Takasawa N, Mashiyama Y, Ishii A, Kassai R. Interventions for body weight reduction in obese patients during short consultations: an open-label randomized controlled trial in the Japanese primary care setting. Asia Pac Fam Med. 2015;14(1):5. doi:10.1186/s12930-015-0022-7
71. Katula JA, Vitolins MZ, Rosenberger EL, et al. One-year results of a community-based translation of the Diabetes Prevention Program: Healthy-Living Partnerships to Prevent Diabetes (HELP PD) Project [published correction appears in Diabetes Care. 2012;35(2):455]. Diabetes Care. 2011;34(7):1451-1457. doi:10.2337/dc10-2115
72. Kim SH, Abbasi F, Lamendola C, et al. Benefits of liraglutide treatment in overweight and obese older individuals with prediabetes. Diabetes Care. 2013;36(10):3276-3282. doi:10.2337/dc13-0354
73. Knowler WC, Barrett-Connor E, Fowler SE, et al; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. doi:10.1056/NEJMoa0125
74. Krempf M, Louvet JP, Allanic H, Miloradovich T, Joubert JM, Attali JR. Weight reduction and long-term maintenance after 18 months treatment with orlistat for obesity. Int J Obes Relat Metab Disord. 2003;27(5):591-597. doi:10.1038/sj.ijo.0802281
75. Kuller LH, Pettee Gabriel KK, Kinzel LS, et al. The Women on the Move Through Activity and Nutrition (WOMAN) study: final 48-month results. Obesity (Silver Spring). 2012;20(3):636-643. doi:10.1038/oby.2011.80
76. Kulzer B, Hermanns N, Gorges D, Schwarz P, Haak T. Prevention of diabetes self-management program (PREDIAS): effects on weight, metabolic risk factors, and behavioral outcomes. Diabetes Care. 2009;32(7):1143-1146. doi:10.2337/dc08-2141
77. Lindgärde F. The effect of orlistat on body weight and coronary heart disease risk profile in obese patients: the Swedish Multimorbidity Study. J Intern Med. 2000;248(3):245-254. doi:10.1046/j.1365-2796.2000.00720.x
78. Little P, Stuart B, Hobbs FR, et al. An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial. Lancet Diabetes Endocrinol. 2016;4(10):821-828. doi:10.1016/S2213-8587(16)30099-7
79. Luley C, Blaik A, Götz A, et al. Weight loss by telemonitoring of nutrition and physical activity in patients with metabolic syndrome for 1 year. J Am Coll Nutr. 2014;33(5):363-374. doi:10.1080/07315724.2013.875437
80. Ma J, Yank V, Xiao L, et al. Translating the Diabetes Prevention Program lifestyle intervention for weight loss into primary care: a randomized trial. JAMA Intern Med. 2013;173(2):113-121. doi:10.1001/2013.jamainternmed.987
81. Marrero DG, Palmer KN, Phillips EO, Miller-Kovach K, Foster GD, Saha CK. Comparison of commercial and self-initiated weight loss programs in people with prediabetes: a randomized control trial. Am J Public Health. 2016;106(5):949-956. doi:10.2105/AJPH.2015.303035
82. Martin CK, Redman LM, Zhang J, et al. Lorcaserin, a 5-HT(2C) receptor agonist, reduces body weight by decreasing energy intake without influencing energy expenditure. J Clin Endocrinol Metab. 2011;96(3):837-845. doi:10.1210/jc.2010-1848
83. Martin PD, Dutton GR, Rhode PC, Horswell RL, Ryan DH, Brantley PJ. Weight loss maintenance following a primary care intervention for low-income minority women. Obesity (Silver Spring). 2008;16(11):2462-2467. doi:10.1038/oby.2008.399
84. Mitsui T, Shimaoka K, Tsuzuku S, Kajioka T, Sakakibara H. Gentle exercise of 40 minutes with dietary counseling is effective in treating metabolic syndrome. Tohoku J Exp Med. 2008;215(4):355-361. doi:10.1620/tjem.215.355
85. Moore H, Summerbell CD, Greenwood DC, et al. Improving management of obesity in primary care: cluster randomised trial. BMJ. 2003;327(7423):1085. doi:10.1136/bmj.327.7423.1085
86. Morgan PJ, Lubans DR, Collins CE, Warren JM, Callister R. 12-month outcomes and process evaluation of the SHED-IT RCT: an internet-based weight loss program targeting men. Obesity (Silver Spring). 2011;19(1):142-151. doi:10.1038/oby.2010.119
87. Muls E, Kolanowski J, Scheen A, Van Gaal L; ObelHyx Study Group. The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study. Int J Obes Relat Metab Disord. 2001;25(11):1713-1721. doi:10.1038/sj.ijo.0801814
88. Nakade M, Aiba N, Suda N, et al; SCOP Group. Behavioral change during weight loss program and one-year follow-up: Saku Control Obesity Program (SCOP) in Japan. Asia Pac J Clin Nutr. 2012;21(1):22-34.
89. Nanchahal K, Power T, Holdsworth E, et al. A pragmatic randomised controlled trial in primar care of the Camden Weight Loss (CAMWEL) programme. BMJ Open. 2012;2(3):e000793. doi:10.1136/bmjopen-2011-000793
90. Narayan KM, Hoskin M, Kozak D, et al. Randomized clinical trial of lifestyle interventions in Pima Indians: a pilot study. Diabet Med. 1998;15(1):66-72. doi:10.1002/(SICI)1096-9136(199801)15:1<66::AID-DIA515>3.0.CO;2-A
91. Nicklas JM, Zera CA, England LJ, et al. A web-based lifestyle intervention for women with recent gestational diabetes mellitus: a randomized controlled trial. Obstet Gynecol. 2014;124(3):563-570. doi:10.1097/AOG.0000000000000420
92. Ockene IS, Tellez TL, Rosal MC, et al. Outcomes of a Latino community-based intervention for the prevention of diabetes: the Lawrence Latino Diabetes Prevention Project. Am J Public Health. 2012;102(2):336-342. doi:10.2105/AJPH.2011.300357
93. Pacanowski CR, Levitsky DA. Frequent self-weighing and visual feedback for weight loss in overweight adults. J Obes. 2015;2015:763680. doi:10.1155/2015/763680
94. Parikh P, Simon EP, Fei K, Looker H, Goytia C, Horowitz CR. Results of a pilot diabetes prevention intervention in East Harlem, New York City: Project HEED. Am J Public Health. 2010;100(suppl 1):S232-S239. doi:10.2105/AJPH.2009.170910
95. Patrick K, Calfas KJ, Norman GJ, et al. Outcomes of a 12-month web-based intervention for overweight and obese men. Ann Behav Med. 2011;42(3):391-401. doi:10.1007/s12160-011-9296-7
96. Pekkarinen T, Kaukua J, Mustajoki P. Long-term weight maintenance after a 17-week weight loss intervention with or without a one-year maintenance program: a randomized controlled trial. J Obes. 2015;2015:651460. doi:10.1155/2015/651460
97. Penn L, White M, Oldroyd J, Walker M, Alberti KG, Mathers JC. Prevention of type 2 diabetes in adults with impaired glucose tolerance: the European Diabetes Prevention RCT in Newcastle upon Tyne, UK. BMC Public Health. 2009;9:342. doi:10.1186/1471-2458-9-342
98. Perri MG, McAllister DA, Gange JJ, Jordan RC, McAdoo G, Nezu AM. Effects of four maintenance programs on the long-term management of obesity. J Consult Clin Psychol. 1988;56(4):529-534. doi:10.1037/0022-006X.56.4.529
99. Pi-Sunyer X, Astrup A, Fujioka K, et al; SCALE Obesity and Prediabetes NN8022-1839 Study Group. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373(1):11-22. doi:10.1056/NEJMoa1411892
100. Puhkala J, Kukkonen-Harjula K, Mansikkamäki K, et al. Lifestyle counseling to reduce body weight and cardiometabolic risk factors among truck and bus drivers—a randomized controlled trial. Scand J Work Environ Health. 2015;41(1):54-64. doi:10.5271/sjweh.3463
101. Richelsen B, Tonstad S, Rössner S, et al. Effect of orlistat on weight regain and cardiovascular risk factors following a very-low-energy diet in abdominally obese patients: a 3-year randomized, placebo-controlled study. Diabetes Care. 2007;30(1):27-32. doi:10.2337/dc06-0210
102. Rock CL, Flatt SW, Byers TE, et al. Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) trial: a behavioral weight loss intervention in overweight or obese breast cancer survivors. J Clin Oncol. 2015;33(28):3169-3176. doi:10.1200/JCO.2015.61.1095
103. Rock CL, Pakiz B, Flatt SW, Quintana EL. Randomized trial of a multifaceted commercial weight loss program. Obesity (Silver Spring). 2007;15(4):939-949. doi:10.1038/oby.2007.614
104. Rosas LG, Thiyagarajan S, Goldstein BA, et al. The effectiveness of two community-based weight loss strategies among obese, low-income US Latinos. J Acad Nutr Diet. 2015;115(4):537-50. doi:10.1016/j.jand.2014.10.020
105. Ross R, Lam M, Blair SN, et al. Trial of prevention and reduction of obesity through active living in clinical settings: a randomized controlled trial. Arch Intern Med. 2012;172(5):414-424. doi:10.1001/archinternmed.2011.1972
106. Rössner S, Sjöström L, Noack R, Meinders AE, Noseda G; European Orlistat Obesity Study Group. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res. 2000;8(1):49-61. doi:10.1038/oby.2000.8
107. Shapiro JR, Koro T, Doran N, et al. Text4Diet: a randomized controlled study using text messaging for weight loss behaviors. Prev Med. 2012;55(5):412-417. doi:10.1016/j.ypmed.2012.08.011
108. Sherwood NE, Crain AL, Martinson BC, et al. Enhancing long-term weight loss maintenance: 2 year results from the Keep It Off randomized controlled trial. Prev Med. 2013;56(3-4):171-177. doi:10.1016/j.ypmed.2012.12.014
109. Silva MN, Vieira PN, Coutinho SR, et al. Using self-determination theory to promote physical activity and weight control: a randomized controlled trial in women. J Behav Med. 2010;33(2):110-122. doi:10.1007/s10865-009-9239-y
110. Simpson SA, McNamara R, Shaw C, et al. A feasibility randomised controlled trial of a motivational interviewing–based intervention for weight loss maintenance in adults. Health Technol Assess. 2015;19(50):1-378. doi:10.3310/hta19500
111. Sjöström L, Rissanen A, Andersen T, et al; European Multicentre Orlistat Study Group. Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. Lancet. 1998;352(9123):167-172. doi:10.1016/S0140-6736(97)11509-4
112. Smith SR, Stenlof KS, Greenway FL, et al. Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial. Obesity (Silver Spring). 2011;19(9):1796-1803. doi:10.1038/oby.2011.143
113. Smith SR, Weissman NJ, Anderson CM, et al; Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) Study Group. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363(3):245-256. doi:10.1056/NEJMoa0909809
114. Smith TJ, Crombie A, Sanders LF, et al. Efficacy of orlistat 60 mg on weight loss and body fat mass in US Army soldiers. J Acad Nutr Diet. 2012;112(4):533-540. doi:10.1016/j.jada.2011.10.006
115. Stevens VJ, Corrigan SA, Obarzanek E, et al; TOHP Collaborative Research Group. Weight loss intervention in phase 1 of the Trials of Hypertension Prevention. Arch Intern Med. 1993;153(7):849-858. doi:10.1001/archinte.1993.00410070039006
116. Stevens VJ, Obarzanek E, Cook NR, et al; Trials for the Hypertension Prevention Research Group. Long-term weight loss and changes in blood pressure: results of the Trials of Hypertension Prevention, Phase II. Ann Intern Med. 2001;134(1):11. doi:10.7326/0003-4819-134-1-200101020-00007
117. Svetkey LP, Batch BC, Lin PH, et al. Cell phone intervention for you (CITY): a randomized, controlled trial of behavioral weight loss intervention for young adults using mobile technology [published correction appears in Obesity (Silver Spring). 2016;24(2):536]. Obesity (Silver Spring). 2015;23(11):2133-2141. doi:10.1002/oby.21226
118. Svetkey LP, Stevens VJ, Brantley PJ, et al; Weight Loss Maintenance Collaborative Research Group. Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. JAMA. 2008;299(10):1139-1148. doi:10.1001/jama.299.10.1139
119. Swinburn BA, Carey D, Hills AP, et al. Effect of orlistat on cardiovascular disease risk in obese adults. Diabetes Obes Metab. 2005;7(3):254-262. doi:10.1111/j.1463-1326.2004.00467.x
120. Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. XENical in the prevention of Diabetes in Obese Subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients. Diabetes Care. 2004;27(1):155-161. doi:10.2337/diacare.27.1.155
121. Tsai AG, Wadden TA, Rogers MA, Day SC, Moore RH, Islam BJ. A primary care intervention for weight loss: results of a randomized controlled pilot study. Obesity (Silver Spring). 2010;18(8):1614-1618. doi:10.1038/oby.2009.457
122. Tuomilehto J, Lindström J, Eriksson JG, et al; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343-1350. doi:10.1056/NEJM200105033441801
123. Van Gaal LF, Broom JI, Enzi G, Toplak H; Orlistat Dose-Ranging Study Group. Efficacy and tolerability of orlistat in the treatment of obesity: a 6-month dose-ranging study. Eur J Clin Pharmacol. 1998;54(2):125-132. doi:10.1007/s002280050433
124. van Wier MF, Dekkers JC, Hendriksen IJ, et al. Effectiveness of phone and e-mail lifestyle counseling for long term weight control among overweight employees. J Occup Environ Med. 2011;53(6):680-686. doi:10.1097/JOM.0b013e31821f2bbb
125. Voils CI, Olsen MK, Gierisch JM, et al. Maintenance of weight loss after initiation of nutrition training: a randomized trial. Ann Intern Med. 2017;166(7):463-471. doi:10.7326/M16-2160
126. von Gruenigen V, Frasure H, Kavanagh MB, et al. Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEED): a randomized controlled trial. Gynecol Oncol. 2012;125(3):699-704. doi:10.1016/j.ygyno.2012.03.042
127. Wadden TA, Volger S, Sarwer DB, et al. A two-year randomized trial of obesity treatment in primary care practice. N Engl J Med. 2011;365(21):1969-1979. doi:10.1056/NEJMoa1109220
128. Wadden TA, Foreyt JP, Foster GD, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity (Silver Spring). 2011;19(1):110-120. doi:10.1038/oby.2010.147
129. Wadden TA, Hollander P, Klein S, et al; NN8022-1923 Investigators. Weight maintenance and additional weight loss with liraglutide after low-calorie-diet-induced weight loss: the SCALE Maintenance randomized study [published corrections appear in Int J Obes (Lond). 2015;39(1):187, 2013;37(11):1514, and 2015;39(1):187]. Int J Obes (Lond). 2013;37(11):1443-1451. doi:10.1038/ijo.2013.120
130. Wing RR, Tate DF, Gorin AA, Raynor HA, Fava JL. A self-regulation program for maintenance of weight loss. N Engl J Med. 2006;355(15):1563-1571. doi:10.1056/NEJMoa061883
131. Wing RR, Venditti E, Jakicic JM, Polley BA, Lang W. Lifestyle intervention in overweight individuals with a family history of diabetes. Diabetes Care. 1998;21(3):350-359. doi:10.2337/diacare.21.3.350
132. Wylie-Rosett J, Swencionis C, Ginsberg M, et al. Computerized weight loss intervention optimizes staff time: the clinical and cost results of a controlled clinical trial conducted in a managed care setting. J Am Diet Assoc. 2001;101(10):1155-1162. doi:10.1016/S0002-8223(01)00284-X
133. Yeh MC, Heo M, Suchday S, et al. Translation of the Diabetes Prevention Program for diabetes risk reduction in Chinese immigrants in New York City. Diabet Med. 2016;33(4):547-551. doi:10.1111/dme.12848
134. Young MD, Callister R, Collins CE, Plotnikoff RC, Aguiar EJ, Morgan PJ. Efficacy of a gender-tailored intervention to prevent weight regain in men over 3 years: a weight loss maintenance RCT. Obesity (Silver Spring). 2017;25(1):56-65. doi:10.1002/oby.21696
135. Beeken RJ, Leurent B, Vickerstaff V, et al. A brief intervention for weight control based on habit-formation theory delivered through primary care: results from a randomised controlled trial. Int J Obes (Lond). 2017;41(2):246-254. doi:10.1038/ijo.2016.206
136. Fischer HH, Fischer IP, Pereira RI, et al. Text message support for weight loss in patients with prediabetes: a randomized clinical trial. Diabetes Care. 2016;39(8):1364-1370. doi:10.2337/dc15-2137
137. Jenkins DJ, Boucher BA, Ashbury FD, et al. Effect of current dietary recommendations on weight loss and cardiovascular risk factors. J Am Coll Cardiol. 2017;69(9):1103-1112. doi:10.1016/j.jacc.2016.10.089
138. O’Brien MJ, Perez A, Scanlan AB, et al. PREVENT-DM comparative effectiveness trial of lifestyle intervention and metformin. Am J Prev Med. 2017;52(6):788-797. doi:10.1016/j.amepre.2017.01.008
139. Thomas JG, Raynor HA, Bond DS, et al. Weight loss in Weight Watchers Online with and without an activity tracking device compared to control: a randomized trial. Obesity (Silver Spring). 2017;25(6):1014-1021. doi:10.1002/oby.21846
140. Ahern AL, Wheeler GM, Aveyard P, et al. Extended and standard duration weight-loss programme referrals for adults in primary care (WRAP): a randomised controlled trial. Lancet. 2017;389(10085):2214-2225. doi:10.1016/S0140-6736(17)30647-5
141. Logue E, Sutton K, Jarjoura D, Smucker W, Baughman K, Capers C. Transtheoretical model–chronic disease care for obesity in primary care: a randomized trial. Obes Res. 2005;13(5):917-927. doi:10.1038/oby.2005.106
142. Mensink M, Corpeleijn E, Feskens EJ, et al. Study on lifestyle-intervention and impaired glucose tolerance Maastricht (SLIM): design and screening results. Diabetes Res Clin Pract. 2003;61(1):49-58. doi:10.1016/S0168-8227(03)00067-6
143. Whelton PK, Appel LJ, Espeland MA, et al; TONE Collaborative Research Group. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). JAMA. 1998;279(11):839-846. doi:10.1001/jama.279.11.839
144. Nilsen V, Bakke PS, Gallefoss F. Effects of lifestyle intervention in persons at risk for type 2 diabetes mellitus—results from a randomised, controlled trial. BMC Public Health. 2011;11:893. doi:10.1186/1471-2458-11-893
145. Kumanyika SK, Fassbender JE, Sarwer DB, et al. One-year results of the Think Health! study of weight management in primary care practices. Obesity (Silver Spring). 2012;20(6):1249-1257. doi:10.1038/oby.2011.329
146. Rodriguez-Cristobal JJ, Alonso-Villaverde C, Panisello JM, et al. Effectiveness of a motivational intervention on overweight/obese patients in the primary healthcare: a cluster randomized trial. BMC Fam Pract. 2017;18(1):74. doi:10.1186/s12875-017-0644-y
147. Phelan S, Hagobian T, Brannen A, et al. Effect of an internet-based program on weight loss for low-income postpartum women: a randomized clinical trial. JAMA. 2017;317(23):2381-2391. doi:10.1001/jama.2017.7119
148. Trials of Hypertension Prevention Collaborative Research Group. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels: results of the Trials of Hypertension Prevention, Phase I. JAMA. 1992;267(9):1213-1220. doi:10.1001/jama.1992.03480090061028
149. Uusitupa M, Peltonen M, Lindström J, et al; Finnish Diabetes Prevention Study Group. Ten-year mortality and cardiovascular morbidity in the Finnish Diabetes Prevention Study—secondary analysis of the randomized trial. PLoS One. 2009;4(5):e5656. doi:10.1371/journal.pone.0005656
150. Shea MK, Nicklas BJ, Houston DK, et al. The effect of intentional weight loss on all-cause mortality in older adults: results of a randomized controlled weight-loss trial. Am J Clin Nutr. 2011;94(3):839-846. doi:10.3945/ajcn.110.006379
151. Ratner R, Goldberg R, Haffner S, et al; Diabetes Prevention Program Research Group. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the Diabetes Prevention Program. Diabetes Care. 2005;28(4):888-894. doi:10.2337/diacare.28.4.888
152. Rubin RR, Peyrot M, Wang NY, et al. Patient-reported outcomes in the practice-based opportunities for weight reduction (POWER) trial. Qual Life Res. 2013;22(9):2389-2398. doi:10.1007/s11136-013-0363-3
153. Florez H, Pan Q, Ackermann RT, et al; Diabetes Prevention Program Research Group. Impact of lifestyle intervention and metformin on health-related quality of life: the Diabetes Prevention Program randomized trial. J Gen Intern Med. 2012;27(12):1594-1601. doi:10.1007/s11606-012-2122-5
154. Ackermann RT, Edelstein SL, Narayan KM, et al; Diabetes Prevention Program Research Group. Changes in health state utilities with changes in body mass in the Diabetes Prevention Program. Obesity (Silver Spring). 2009;17(12):2176-2181. doi:10.1038/oby.2009.114
155. Demark-Wahnefried W, Colditz GA, Rock CL, et al; ENERGY Trial Group. Quality of life outcomes from the Exercise and Nutrition Enhance Recovery and Good Health for You (ENERGY) randomized weight loss trial among breast cancer survivors. Breast Cancer Res Treat. 2015;154(2):329-337. doi:10.1007/s10549-015-3627-5
156. McCarroll ML, Armbruster S, Frasure HE, et al. Self-efficacy, quality of life, and weight loss in overweight/obese endometrial cancer survivors (SUCCEED): a randomized controlled trial. Gynecol Oncol. 2014;132(2):397-402. doi:10.1016/j.ygyno.2013.12.023
157. Sarwer DB, Moore RH, Diewald LK, et al; POWER-UP Research Group. The impact of a primary care-based weight loss intervention on the quality of life. Int J Obes (Lond). 2013;37(suppl 1):S25-S30. doi:10.1038/ijo.2013.93
158. Swencionis C, Wylie-Rosett J, Lent MR, et al. Weight change, psychological well-being, and vitality in adults participating in a cognitive-behavioral weight loss program. Health Psychol. 2013;32(4):439-446. doi:10.1037/a0029186
159. Lindström J, Peltonen M, Eriksson JG, et al; Finnish Diabetes Prevention Study (DPS). Improved lifestyle and decreased diabetes risk over 13 years: long-term follow-up of the randomised Finnish Diabetes Prevention Study (DPS). Diabetologia. 2013;56(2):284-293. doi:10.1007/s00125-012-2752-5
160. le Roux CW, Astrup A, Fujioka K, et al; SCALE Obesity Prediabetes NN8022-1839 Study Group. 3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial. Lancet. 2017;389(10077):1399-1409. doi:10.1016/S0140-36(17)30069-7
161. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in never-smoking overweight US white women aged 40-64 years. Am J Epidemiol. 1995;141(12):1128-1141. doi:10.1093/oxfordjournals.aje.a117386
162. Wannamethee SG, Shaper AG, Walker M. Overweight and obesity and weight change in middle aged men: impact on cardiovascular disease and diabetes. J Epidemiol Community Health. 2005;59(2):134-139. doi:10.1136/jech.2003.015651
163. Gregg EW, Gerzoff RB, Thompson TJ, Williamson DF. Intentional weight loss and death in overweight and obese U.S. adults 35 years of age and older. Ann Intern Med. 2003;138(5):383-389. doi:10.7326/0003-4819-138-5-200303040-00007
164. Parker ED, Folsom AR. Intentional weight loss and incidence of obesity-related cancers: the Iowa Women’s Health Study. Int J Obes Relat Metab Disord. 2003;27(12):1447-1452. doi:10.1038/sj.ijo.0802437
165. Danaei G, Robins JM, Young JG, Hu FB, Manson JE, Hernán MA. Weight loss and coronary heart disease: sensitivity analysis for unmeasured confounding by undiagnosed disease. Epidemiology. 2016;27(2):302-310.
166. Wijnhoven HA, van Zon SK, Twisk J, Visser M. Attribution of causes of weight loss and weight gain to 3-year mortality in older adults: results from the Longitudinal Aging Study Amsterdam. J Gerontol A Biol Sci Med Sci. 2014;69(10):1236-1243. doi:10.1093/gerona/glu005
167. French SA, Folsom AR, Jeffery RW, Williamson DF. Prospective study of intentionality of weight loss and mortality in older women: the Iowa Women’s Health Study. Am J Epidemiol. 1999;149(6):504-514. doi:10.1093/oxfordjournals.aje.a009844
168. Williamson DF, Pamuk E, Thun M, Flanders D, Byers T, Heath C. Prospective study of intentional weight loss and mortality in overweight white men aged 40-64 years. Am J Epidemiol. 1999;149(6):491-503. doi:10.1093/oxfordjournals.aje.a009843
169. Sørensen TI, Rissanen A, Korkeila M, Kaprio J. Intention to lose weight, weight changes, and 18-y mortality in overweight individuals without co-morbidities. PLoS Med. 2005;2(6):e171. doi:10.1371/journal.pmed.0020171
170. Yaari S, Goldbourt U. Voluntary and involuntary weight loss: associations with long-term mortality in 9,228 middle-aged and elderly men. Am J Epidemiol. 1998;148(6):546-555. doi:10.1093/oxfordjournals.aje.a009680
171. Courcoulas AP, Goodpaster BH, Eagleton JK, et al. Surgical vs medical treatments for type 2 diabetes mellitus: a randomized clinical trial. JAMA Surg. 2014;149(7):707-715. doi:10.1001/jamasurg.2014.467
172. Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012. JAMA Surg. 2014;149(3):275-287. doi:10.1001/jamasurg.2013.3654
173. Sarkhosh K, Switzer NJ, El-Hadi M, Birch DW, Shi X, Karmali S. The impact of bariatric surgery on obstructive sleep apnea: a systematic review. Obes Surg. 2013;23(3):414-423. doi:10.1007/s11695-012-0862-2
174. Sarwer DB, Wadden TA, Moore RH, Eisenberg MH, Raper SE, Williams NN. Changes in quality of life and body image after gastric bypass surgery. Surg Obes Relat Dis. 2010;6(6):608-614. doi:10.1016/j.soard.2010.07.015
175. Dawes AJ, Maggard-Gibbons M, Maher AR, et al. Mental health conditions among patients seeking and undergoing bariatric surgery: a meta-analysis. JAMA. 2016;315(2):150-163. doi:10.1001/jama.2015.18118
176. King WC, Chen JY, Belle SH, et al. Change in pain and physical function following bariatric surgery for severe obesity. JAMA. 2016;315(13):1362-1371. doi:10.1001/jama.2016.3010
177. Kamvissi-Lorenz V, Raffaelli M, Bornstein S, Mingrone G. Role of the gut on glucose homeostasis: lesson learned from metabolic surgery. Curr Atheroscler Rep. 2017;19(2):9. doi:10.1007/s11883-017-0642-5
178. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005;82(1)(suppl):222S-225S. doi:10.1093/ajcn/82.1.222S
179. Weiss EC, Galuska DA, Kettel Khan L, Gillespie C, Serdula MK. Weight regain in U.S. adults who experienced substantial weight loss, 1999-2002. Am J Prev Med. 2007;33(1):34-40. doi:10.1016/j.amepre.2007.02.040
180. Puhl RM, Quinn DM, Weisz BM, Suh YJ. The role of stigma in weight loss maintenance among U.S. adults. Ann Behav Med. 2017;51(5):754-763. doi:10.1007/s12160-017-9898-9
181. Kruseman M, Schmutz N, Carrard I. Long-term weight maintenance strategies are experienced as a burden by persons who have lost weight compared to persons with a lifetime normal, stable weight. Obes Facts. 2017;10(4):373-385. doi:10.1159/000478096
182. Vieira PN, Silva MN, Mata J, et al. Correlates of health-related quality of life, psychological well-being, and eating self-regulation after successful weight loss maintenance. J Behav Med. 2013;36(6):601-610. doi:10.1007/s10865-012-9454-9
183. Feller S, Müller A, Mayr A, Engeli S, Hilbert A, de Zwaan M. What distinguishes weight loss maintainers of the German Weight Control Registry from the general population? Obesity (Silver Spring). 2015;23(5):1112-1118. doi:10.1002/oby.21054
184. Dulloo AG, Montani JP. Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview. Obes Rev. 2015;16(suppl 1):1-6. doi:10.1111/obr.12250
185. Mackie GM, Samocha-Bonet D, Tam CS. Does weight cycling promote obesity and metabolic risk factors? Obes Res Clin Pract. 2017;11(2):131-139. doi:10.1016/j.orcp.2016.10.284
186. DerSarkissian M, Bhak RH, Huang J, et al. Maintenance of weight loss or stability in subjects with obesity: a retrospective longitudinal analysis of a real-world population. Curr Med Res Opin. 2017;33(6):1105-1110. doi:10.1080/03007995.2017.1307173
187. Abell JE, Egan BM, Wilson PW, Lipsitz S, Woolson RF, Lackland DT. Age and race impact the association between BMI and CVD mortality in women. Public Health Rep. 2007;122(4):507-512. doi:10.1177/003335490712200412
188. Abell JE, Egan BM, Wilson PW, Lipsitz S, Woolson RF, Lackland DT. Differences in cardiovascular disease mortality associated with body mass between black and white persons. Am J Public Health. 2008;98(1):63-66. doi:10.2105/AJPH.2006.093781
189. Chen Y, Henson S, Jackson AB, Richards JS. Obesity intervention in persons with spinal cord injury. Spinal Cord. 2006;44(2):82-91. doi:10.1038/sj.sc.3101818
190. Low S, Chin MC, Ma S, Heng D, Deurenberg-Yap M. Rationale for redefining obesity in Asians. Ann Acad Med Singapore. 2009;38(1):66-69.
191. Maskarinec G, Grandinetti A, Matsuura G, et al. Diabetes prevalence and body mass index differ by ethnicity: the Multiethnic Cohort. Ethn Dis. 2009;19(1):49-55.
192. Ni Mhurchu C, Rodgers A, Pan WH, Gu DF, Woodward M; Asia Pacific Cohort Studies Collaboration. Body mass index and cardiovascular disease in the Asia-Pacific Region: an overview of 33 cohorts involving 310,000 participants. Int J Epidemiol. 2004;33(4):751-758. doi:10.1093/ije/dyh163
193. Huxley R, Barzi F, Lee CM, et al; Obesity in Asia Collaboration. Waist circumference thresholds provide an accurate and widely applicable method for the discrimination of diabetes. Diabetes Care. 2007;30(12):3116-3118. doi:10.2337/dc07-1455
194. Razak F, Anand S, Vuksan V, et al; SHARE Investigators. Ethnic differences in the relationships between obesity and glucose-metabolic abnormalities: a cross-sectional population-based study. Int J Obes (Lond). 2005;29(6):656-667. doi:10.1038/sj.ijo.0802937
195. Razak F, Anand SS, Shannon H, et al. Defining obesity cut points in a multiethnic population. Circulation. 2007;115(16):2111-2118. doi:10.116/CIRCULATIONAHA.106.635011
196. Sánchez-Castillo CP, Velázquez-Monroy O, Berber A, Lara-Esqueda A, Tapia-Conyer R, James WP; Encuesta Nacional de Salud (ENSA) 2000 Working Group. Anthropometric cutoff points for predicting chronic diseases in the Mexican National Health Survey 2000. Obes Res. 2003;11(3):442-451. doi:10.1038/oby.2003.60
197. Stevens J, Juhaeri, Cai J, Jones DW. The effect of decision rules on the choice of a body mass index cutoff for obesity: examples from African American and white women. Am J Clin Nutr. 2002;75(6):986-992. doi:10.1093/ajcn/75.6.986
198. Stommel M, Schoenborn CA. Variations in BMI and prevalence of health risks in diverse racial and ethnic populations. Obesity (Silver Spring). 2010;18(9):1821-1826. doi:10.1038/oby.2009.472
199. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. 2004;363(9403):157-163. doi:10.1016/S0140-6736(03)15268-3
200. Wen CP, David Cheng TY, Tsai SP, et al. Are Asians at greater mortality risks for being overweight than Caucasians? redefining obesity for Asians. Public Health Nutr. 2009;12(4):497-506. doi:10.1017/S1368980008002802
201. Jackson CL, Wang NY, Yeh HC, Szklo M, Dray-Spira R, Brancati FL. Body-mass index and mortality risk in U.S. blacks compared to whites. Obesity (Silver Spring). 2014;22(3):842-851. doi:10.1002/oby.20471
202. Adams KF, Schatzkin A, Harris TB, et al. Overweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old. N Engl J Med. 2006;355(8):763-778. doi:10.1056/NEJMoa055643
203. Whitlock G, Lewington S, Sherliker P, et al; Prospective Studies Collaboration. Body-mass index and cause-specific mortality in 900,000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083-1096. doi:10.1016/S0140-6736(09)60318-4
204. Danaei G, Ding EL, Mozaffarian D, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med. 2009;6(4):e1000058. doi:10.1371/journal.pmed.1000058
205. Peeters A, Barendregt JJ, Willekens F, Mackenbach JP, Al Mamun A, Bonneux L; Netherlands Epidemiology and Demography Compression of Morbidity Research Group. Obesity in adulthood and its consequences for life expectancy: a life-table analysis. Ann Intern Med. 2003;138(1):24-32. doi:10.7326/0003-4819-138-1-200301070-00008
206. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med. 2010;363(23):2211-2219. doi:10.1056/NEJMoa1000367
207. Di Angelantonio E, Bhupathiraju ShN, Wormser D, et al; Global BMI Mortality Collaboration. Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents. Lancet. 2016;388(10046):776-786. doi:10.1016/S0140-6736(16)30175-1
208. Flegal KM, Williamson DF, Pamuk ER, Rosenberg HM. Estimating deaths attributable to obesity in the United States. Am J Public Health. 2004;94(9):1486-1489. doi:10.2105/AJPH.94.9.1486
209. Calle EE, Thun MJ, Petrelli JM, Rodriguez C, Heath CW Jr. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341(15):1097-1105. doi:10.1056/NEJM199910073411501
210. Lenz M, Richter T, Mühlhauser I. The morbidity and mortality associated with overweight and obesity in adulthood: a systematic review. Dtsch Arztebl Int. 2009;106(40):641-648.
211. Flegal KM, Kit BK, Orpana H, Graubard BI. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis. JAMA. 2013;309(1):71-82. doi:10.1001/jama.2012.113905
212. Yu E, Ley SH, Manson JE, et al. Weight history and all-cause and cause-specific mortality in three prospective cohort studies. Ann Intern Med. 2017;166(9):613-620. doi:10.7326/M16-1390
213. Flegal KM, Ioannidis JP. A meta-analysis but not a systematic review: an evaluation of the Global BMI Mortality Collaboration. J Clin Epidemiol. 2017;88:21-29. doi:10.1016/j.jclinepi.2017.04.007
214. Padwal RS, Pajewski NM, Allison DB, Sharma AM. Using the Edmonton obesity staging system to predict mortality in a population-representative cohort of people with overweight and obesity. CMAJ. 2011;183(14):E1059-E1066. doi:10.1503/cmaj.110387
215. Sharma AM, Campbell-Scherer DL. Redefining obesity: beyond the numbers. Obesity (Silver Spring) 2017;25(4):660-661. doi:10.1002/oby.21801
Evidence reviews for the US Preventive Services Task Force (USPSTF) use an analytic framework to visually display the key questions that the review will address to allow the USPSTF to evaluate the effectiveness and safety of a preventive service. The questions are depicted by linkages that relate interventions and outcomes. A dashed line indicates a relationship between an intermediate outcome and a health outcome that is presumed to describe the natural progression of the disease. Refer to the USPSTF Procedure Manual for further details.16
Reasons for exclusion: Aim: Study aim was not relevant. Setting: Study was not conducted in a country relevant to United States practice or not conducted in, recruited from, or feasible for primary care or a health system. No relevant outcomes: Study did not have relevant outcomes or had incomplete outcomes. Reporting of outcomes: Outcomes not presented in a way that could be abstracted for the review. Population inclusion criteria: Study was not conducted in an included population. Population not generalizable or relevant: Included population was not generalizable to a primary care population. Chronic disease management: Aim of the intervention was the management of an existing chronic disease. Intervention: Intervention was out of scope. Excluded study design: Study did not use an included design. <12 months of follow-up: Follow-up for health or weight loss outcomes was less than 12 months. Not an included comparator: Comparator did not meet review criteria. Language: Publication not in English. Quality: Study was poor quality. Protocol only: Publication represented a study protocol without an identified publication of full study results. Unable to locate: Full text not available. USPSTF indicates US Preventive Services Task Force.
|Intervention||Control||Study-Reported Between-Group Mean Difference (95% CI or SD)||Study Quality|
|Group||No.||Instrument||Mean (SD) Score at Baseline||Mean Change
(95% CI or SD)
|No.||Mean (SD) Score at Baseline||Mean Change
(95% CI or SD)
Ahern et al,140
|12||1||504||EQ5D-3L||0.793 (0.249)||−0.012 (0.011)a||197||0.786 (0.266)||−0.014 (0.018)a||0.014 (−0.025 to 0.054)
P = 0.476
|2||508||0.783 (0.249)||0.009 (0.011)a||197||0.786 (0.266)||−0.014 (0.018)a||0.029 (−0.011 to 0.069)
P = 0.150
|24||1||504||0.793 (0.249)||−0.018 (0.011)a||197||0.786 (0.266)||−0.005 (0.018)a||−0.014 (−0.052 to 0.025)
P = 0.486
|2||508||0.783 (0.249)||−0.015 (0.012)a||197||0.786 (0.266)||−0.005 (0.018)a||−0.011 (−0.050 to 0.028)
P = 0.486
Appel et al,29 2011
Rubin et al,152 2013b
|24||1||100||SF-12 mental||52.16 (9.60)||−0.50 (0.76)a||88||51.06 (8.71)||0.62 (0.95)a||−1.12 (−3.52 to 1.27)||Good|
|SF-12 physical||47.06 (8.92)||2.23 (0.75)||46.83 (7.95)||−0.29 (0.97)||2.52 (0.11 to 4.93)
P < 0.05
|EQ-5D VAS||75.12 (18.95)||6.14 (1.78)||73.34 (17.63)||4.31 (1.77)||1.83 (−3.07 to 6.7)|
|EQ-5D single index||0.88 (0.12)||−0.01 (0.01)||0.87 (0.11)||−0.01 (0.01)||−0.0003 (−0.04 to 0.03)|
|2||115||SF-12 mental||47.53 (8.42)||1.16 (0.77)||46.83 (7.95)||−0.29 (0.97)||1.45 (−0.99 to 3.90)|
|SF-12 physical||52.53 (7.40)||−1.07 (0.68)||51.06 (8.71)||0.62 (0.95)||−1.70 (−3.99 to 0.60)|
|EQ-5D VAS||76.64 (15.72)||3.45 (1.53)||73.34 (17.63)||4.31 (1.77)||−0.86 (−5.47 to 3.75)|
|EQ-5D single index||0.88 (0.12)||−0.01 (0.01)||0.87 (0.11)||−0.01 (0.01)||−0.004 (−0.04 to 0.03)|
de Vos et al,46 2014
et al,47 2014
|12||1||23||SF-36 mental||56.6 (8.2)||−1.9 (−6.0 to 2.2)||18||53.7 (8.5)||2.4 (−1.0 to 5.8)||P = 0.35||Good|
|2||52.1 (11.7)||0.6 (−3.8 to 5.0)||18||53.7 (8.5)||2.4 (−1.0 to 5.8)||P = 0.46|
|1||23||SF-36 physical||44.3 (8.3)||2.2 (−2.1 to 6.5)||18||45.3 (8.5)||0.9 (−1.4 to 3.2)||P = 0.73|
|2||44.3 (11.9)||−2.3 (−5.0 to 0.4)||18||45.3 (8.5)||0.9 (−1.4 to 3.2)||P = 0.16|
|Waste the Waist
Greaves et al,56 2015
|12||1||55||EQ-5D VAS||77.0 (14.9)||NR||53||76.4 (17.0)||NR||1.36 (−3.37 to 6.04)||Fair|
|Jansson et al,65 2013||12||1||45||SF-36 and EQ-5D||NR||NR||49||NR||NR||NRc||Fair|
Hunt et al,62 2014
|12||1||316||SF-36 mental||48.9 (10.1)||1.9 (0.9 to 2.8)||351||48.3 (9.2)||1.6 (0.8 to 2.4)||0.50 (−0.62 to 1.62)
P = 0.3822
|SF-36 physical||47.0 (7.9)||2.3 (1.5 to 3.2)||351||47.7 (7.5)||0.2 (−0.6 to 0.9)||1.89 (0.89 to 2.90)
P = 0.0002
Knowler et al,73 2002d
Florez et al,153 2012e
Ackermann et al,154 2009f
|12||1||1017||SF-36 mental||53.7 (7.6)||−0.70 (8.67)||1018||54.0 (7.4)||−1.16 (8.33)||NR||Good|
|SF-36 physical||50.6 (6.9)||1.33 (7.0)||1018||50.4 (7.2)||−0.04 (7.12)||NR|
|38||1||1048||SF-36 mental||53.7 (7.6)||NR||850||50.4 (7.2)||NR||0.29 (0.32)|
|SF-36 physical||50.6 (6.9)||NR||850||50.4 (7.2)||NR||1.57 (0.30)
P < 0.01
|12||1||268||QWB-SA||0.7 (0.1)||0.02 (0.1)||252||0.7 (0.1)||0.01 (0.1)||NR|
|12||1||1015||SF-6D health utility index||0.8 (0.1)||0.0 (0.1)||1018||0.8 (0.1)||0.01 (0.1)||NR|
|38||1||1048||SF-6D health utility index||0.8 (0.1)||NR||850||0.8 (0.1)||NR||0.01 (0.004)
P < 0.05
Kulzer et al,76 2009d
|12||1||91||WHO-5||15.3 (5.1)||1.4 (3.9)||91||14.3 (4.9)||0.0 (4.2)||1.40 (0.22 to 2.58)
P = 0.101
Nanchahal et al,89 2012
|Ockene et al,92 2012||12||1||147||SF-12||NR||NR||142||NR||NR||NRc||Fair|
|Pekkarinen et al,96 2015g||24||1||50||SF-36||NR||NR||38||NR||NR||NRc||Fair|
Rock et al,102 2015
et al,155 2015
|58.7 (21.35)||NR||244||58.7||NR||P = 0.51||Good|
|80.2 (18.67)||NR||244||79.0 (18.38)||NR||P = 0.05|
|58.7 (21.35)||NR||248||58.7||NR||P = 0.19|
|80.2 (18.67)||NR||248||79.0 (18.38)||NR||P = 0.62|
Simpson et al,110 2015g
|12||1||45||EQ-5D index score||NA||NA||51||NA||NA||OR, 0.85 (0.29 to 2.46)h||Fair|
|2||43||EQ-5D index score||NA||NA||51||NA||NA||OR, 1.39 (0.49 to 3.94)h|
von Gruenigen et al,126
McCarroll et al,156 2014
Wadden et al,127 2011d
Sarwer et al,157 2013
|12||1||131||IWQOL-Lite (total)||69.4 (17.5)||NR||130||68.8 (17.5)||NR||NRc||Good|
|SF-12 mental||48.9 (9.8)||NR||48.7 (10.5)||NR||NRc|
|SF-12 physical||43.9 (9.0)||NR||43.4 (9.5)||NR||NRc|
|EQ-5D index score||70.4 (18.8)||NR||67.0 (20.0)||NR||NRc|
|Wylie-Rosett et al,132
Swencionis et al,158
Abbreviations: CAMWEL, Camden Weight Loss; DAMES, Daughters and Mothers Against Breast Cancer; DPP, Diabetes Prevention Program; ENERGY, Exercise and Nutrition to Enhance Recovery and Good Health for You; EQ-5D, EuroQol Five Dimensions; EQ-5D-3L, 3-level version of EQ-5D; EQ-VAS, EuroQol Visual Analogue Scale; FACT-G, Functional Assessment of Cancer Therapy—General; FFIT, Football Fans in Training; IWQOL, Impact of Weight on Quality of Life; NA, not applicable; NR, not reported; NS, not statistically significant; OR, odds ratio; PA, physical activity; POWER, Practice-based Opportunities for Weight Reduction; POWER-UP, Practice-based Opportunities for Weight Reduction at the University of Pennsylvania; PREDIAS, Prevention of Diabetes Self-Management Program; PROOF, Prevention of Knee Osteoarthritis in Overweight Females; QOL, quality of life; QWB-SA, Quality of Well-Being Index—Self-Administered; SF-6D, Medical Outcomes Study 6-Dimension Short Form; SF-12, Medical Outcomes Study 12-Item Short Form Health Survey; SF-36, Medical Outcomes Study 36-Item Short Form Health Survey; SUCCEED, Survivors of Uterine Cancer Empowered by Exercise and Healthy Diet; VAS, visual analogue scale; WHO-5, WHO (5) Well-Being Index; WILMA, Weight Loss Maintenance in Adults; WRAP, Weight-Loss Program Referrals for Adults in Primary Care.
a Standard error reported in parentheses.
b Study used both the SF-12 and the EQ-5D.
c Study did not report actual values that could be used for a between-group mean difference in score.
d Included in previous review.
e Study used the SF-36 (38 months of follow-up) and SF-6D (38 months of follow-up).
f Study used the SF-6D (12 months of follow-up), QWB-SA, and SF-36 (12 months of follow-up).
g Weight loss maintenance study.
h Reported as dichotomized analysis of participants with scores <100 vs those with scores of 100 because of skewed and bimodal distribution of follow-up scores. The odds of scoring 100 was 15% lower in intervention group 1 than in the control group (OR, 0.85 [95% CI, 0.29 to 2.46]), whereas in intervention group 2 it was 39% greater than in the control group (OR, 1.39 [95% CI, 0.49 to 3.94]).
i Results not reported by group, but no significant differences in well-being were found between groups at 12 months (P = 0.53 for anxiety, P = 0.32 for depression, P = 0.39 for positive well-being, P = 0.11 for self-control, P = 0.38 for general health, P =0 .35 for vitality, P = 0.29 for total well-being).
Difference in Mean Change,
kg (95% CI)a
|No. (%)||No.||Baseline Weight,
Mean (SD) kg
|Mean (95% CI) Change, kg||No.||Baseline Weight, Mean (SD) kg||Mean (95% CI) Change, kg|
|Astrup et al,31 2012||12||121 (63.1)||3.0 mg/d||93||97.5 (13.8)||−7.8 (NR)||98||97.3 (12.3)||−2.0 (NR)||−5.80 (−8.00 to −3.70)||<0.0001|
|Pi-Sunyer et al,99 2015||13||2589 (69.4)||3.0 mg/d||2437||106.2 (21.2)||−8.4 (−8.7 to −8.1)||1225||106.2 (21.7)||−2.8 (−3.2 to −2.4)||−5.60 (−6.00 to −5.10)||<0.001|
|le Roux et al,160 2017||36b||1865 (50.0)||3.0 mg/d||1472||107.5 (21.6)||−6.5 (−6.9 to −6.1)||738||107.9 (21.8)||−2.0 (−2.5 to −1.5)||−4.60 (−5.30 to −3.90)||<0.0001|
|Fidler et al,51 2011||12||1778 (55.5)||10 mg × 2/d||1561||100.3 (15.7)||−5.8 (−6.1 to −5.5)c||1541||100.8 (16.2)||−2.9 (−3.2 to −2.6)c||−2.90 (NR)c||<0.001|
|Smith et al,113 2010||12||1581 (49.7)||10 mg × 2/d||1538||100.4 (16.0)||−5.8 (−6.2 to −5.4)||1499||99.7 (15.9)||−2.2 (−2.4 to−2.0)||−3.60 (−4.04 to −3.16)||<0.001|
|Naltrexone HCL–Bupropion HCL|
|Apovian et al,28 2013||13||805 (53.8)||16/180 mg × 3/d||702||100.3 (16.6)||−6.2 (−6.6 to −5.8)c||456||99.2 (15.9)||−1.3 (−1.9 to −0.7)c||NR||<0.001|
|Greenway et al,57 2010||13||697 (59.9)||16/180 mg × 3/d||471||99.7 (15.9)||−6.1 (−6.7 to −5.5)c||511||99.5 (14.3)||−1.4 (−2.0 to −0.8)c||NR||<0.0001|
|Broom et al,38 2002||12||347 (65.3)||120 mg × 3/d||259||100.9 (20.5)||−5.8 (−6.8 to −4.8)||263||101.8 (19.8)||−2.3 (−3.1 to −1.5)||−3.50 (−4.79 to −2.21)||<0.0001|
|Davidson et al,45 1999||12||591 (66.3)||120 mg × 3/d||657||100.7 (15.4)||−8.8 (−9.5 to −8.0)||223||100.6 (13.4)||−5.8 (−7.1 to −4.5)||−2.95 (−4.45 to −1.45)||<0.001|
|Derosa et al,48 2003||12||48 (96.0)||120 mg × 3/d||25||94.2 (9.8)||−8.6 (−9.0 to −8.2)||23||95.3 (10.2)||−7.6 (−7.9 to −7.3)||−1.00 (−1.49 to −0.51)||NR|
|Finer et al,52 2000||12||139 (61.0)||120 mg × 3/d||110||97.9 (12.9)||−3.3 (NR)c||108||98.4 (15.0)||−1.3 (NR)c||−1.99 (−3.60 to −0.38)c||0.016|
|Hauptman et al,59 2000||12||427 (67.2)||120 mg × 3/d||210||100.5 (14.2)||−7.9 (−9.1 to −6.8)||212||101.8 (14.6)||−4.1 (−5.2 to −3.0)||−3.80 (−5.37 to −2.23)||0.001|
|60 mg × 3/d||213||100.4 (14.6)||−7.1 (−8.1 to −6.0)||212||101.8 (14.6)||−4.1 (−5.2 to −3.0)||−2.94 (−4.46 to −1.42)||0.001|
|18||NR||120 mg × 3/d||210||100.5 (14.2)||−6.2 (−7.4 to −5.0)||212||101.8 (14.6)||−2.9 (−4.0 to −1.8)||−3.29 (−4.94 to −1.64)||0.001|
|60 mg × 3/d||213||100.4 (14.6)||−5.8 (−6.8 to −4.8)||212||101.8 (14.6)||−2.9 (−4.0 to −1.8)||−2.85 (−4.36 to −1.34)||0.001|
|24||328 (51.7)||120 mg × 3/d||210||100.5 (14.2)||−5.0 (−6.5 to −3.6)||212||101.8 (14.6)||−1.6 (−2.9 to −0.4)||−3.37 (−5.25 to −1.49)||0.001|
|60 mg × 3/d||213||100.4 (14.6)||−4.5 (−5.7 to −3.3)||212||101.8 (14.6)||−1.6 (−2.9 to −0.4)||−2.81 (−4.51 to −1.11)||0.001|
|Krempf et al,74 2003||12||478 (68.7)||120 mg × 3/d||346||97.0 (16.7)||−6.3 (−7.3 to −5.3)c||350||97.5 (16.8)||−3.3 (−4.3 to −2.3)c||NR||<0.0001|
|18||425 (61.1)||346||97.0 (16.7)||−5.3 (−6.3 to −4.3)c||350||97.5 (16.8)||−2.4 (−3.4 to −1.4)c||NR||<0.0001|
|Lindgärde,77 2000||12||376 (85.9)||120 mg × 3/d||190||96.1 (13.7)||−5.6 (−6.3 to −4.9)||186||95.9 (13.5)||−4.3 (−5.1 to −3.5)||−1.30 (−2.43 to −0.17)||<0.05|
|Phentermine-Topiramate Extended Release|
|Rössner et al,106 2000||12||524 (71.9)||120 mg × 3/d||242||96.7 (13.8)||−9.4 (−10.2 to −8.6)||237||97.7 (14.6)||−6.4 (−7.3 to −5.5)||−3.00 (−4.17 to −1.83)||<0.001|
|60 mg × 3/d||239||99.1 (14.3)||−8.5 (−9.4 to −7.6)||237||97.7 (14.6)||−6.4 (−7.3 to −5.5)||−2.10 (−3.36 to −0.84)||<0.001|
|24||435 (59.7)||120 mg × 3/d||242||96.7 (13.8)||−7.4 (−8.3 to −6.5)||237||97.7 (14.6)||−4.3 (−5.2 to −3.4)||−3.10 (−4.40 to −1.80)||<0.001|
|60 mg × 3/d||239||99.1 (14.3)||−6.6 (−7.7 to −5.5)||237||97.7 (14.6)||−4.3 (−5.2 to −3.4)||−2.30 (−3.71 to −0.89)||0.005|
|Sjöström et al,111 1998||12||544 (79.1)||120 mg × 3/d||343||99.1 (NR)||10.3 (NR)||340||99.8 (NR)||−6.1 (NR)||−4.20 (NR)||<0.001|
|Swinburn et al,119 2005||12||269 (79.4)||120 mg × 3/d||170||103.3 (17.8)||−4.7 (−5.9 to −3.5)||169||106.9 (17.8)||−0.9 (−1.5 to −0.3)||−3.80 (−5.12 to −2.48)||0.001|
|Torgerson et al,120 2004||12||2746 (83.1)||120 mg × 3/d||1640||110.4 (16.3)||−10.6 (NR)||1637||110.6 (16.5)||−6.2 (NR)||−4.40 (NR)||<0.001|
|48||1414 (42.8)||120 mg × 3/d||1640||110.4 (16.3)||−5.8 (NR)||1637||110.6 (16.5)||−3.0 (NR)||−2.70 (NR)c||0.001|
|Gadde et al,54 2011||13||1723 (69.3)||15/92 mg/d||981||103.0 (17.6)||−10.2 (−10.8 to −9.7)c||979||103.3 (18.1)||1.4 (−2.0 to −0.8)c||NR||<0.0001|
|7.5/46 mg/d||488||102.6 (18.2)||−8.1 (−8.9 to −7.4)c||979||103.3 (18.1)||1.4 (−2.0 to −0.8)c||NR||<0.0001|
Abbreviation: NR, not reported.
a Study-reported adjusted between-group difference in mean change reported if available; otherwise, calculated unadjusted between-group difference.
b Individuals with prediabetes at baseline only.
c Least squares mean.
|Intervention||No. of Studies
(No. of Observations)
|Summary of Findings||Consistency and Precisiona,b||Other Limitations||Strength of Evidence||Applicability|
|KQ1: Health Outcomes|
|Behavior-based weight loss||18 RCTs
|All-cause mortality: 4 trials reported no differences between groups at up to 16-y follow-up
CVD: 2 trials reported no between-group differences in incidence of CVD events after 3 and 10 y of follow-up
QOL: 15 trials reported no consistent effects at ≥1 y follow-up
|Few trials reported CVD morbidity or CVD- or all-cause–related mortality with longer-term follow-up or sufficient power to detect differences
QOL variably measured, and few trials reported absolute values
Reporting bias undetected
|Low for benefit||Trials reporting all-cause mortality and CVD events were limited to adults with obesity with prediabetes or prehypertension|
|Behavior-based weight loss maintenance||2 RCTs
|QOL: No consistent effects of maintenance interventions on QOL after 1- to 2-y follow-up||Inconsistent
|No trials reported health outcomes beyond QOL
QOL data limited and poorly reported
Reporting bias undetected
|Insufficient||Design of trials was mixed, with 1 including a weight loss intervention for all participants within the trial and the other recruiting participants after ≥5% weight loss in the past year
Trials represented a general, unselected population with BMIs ≥30 (in trial with weight loss before study entry) to ≥35 (in trial with weight loss as part of study)c
|Medication-based weight loss||10 RCTs
|CVD: 2 trials reported few events in either group
QOL: 10 trials generally reported improved QOL scores in participants randomized to medications vs placebo
|Number of CVD events low, with insufficient power to detect differences
Trials with high dropout rates and QOL absolute values not reported in 4 of 10 trials
In studies with value, differences were small and of unclear clinical significance
No reporting bias suspected
|Low for benefit||Trials were of highly selected populations with multiple exclusions relevant to health outcomes (eg, history of serious medical conditions, cardiovascular events, psychiatric illness)|
|Medication-based weight loss maintenance||0|
|KQ2: Weight Outcomes|
|Behavior-based weight loss||79 RCTs
|Pooled results of 67 trials indicated greater weight loss from behavior-based weight loss interventions vs control conditions at 12-18 mo (mean difference in weight change, −2.39 kg [95% CI, −2.86 to −1.93]; 67 trials [n = 22,065]; I2 = 90.0%)
Mean absolute changes in weight ranged from −0.5 kg (1.1 lb) to −9.3 kg (20.5 lb) among intervention participants and from 1.4 kg (3.1 lb) to −5.6 (12.3 lb) among control participants
Weight change at follow-up beyond 12-18 mo not as well reported but found consistent, although generally attenuated, effects over time
Heterogeneity within each individual intervention group, confounded with differences in the populations, settings, and trial quality, make it nearly impossible to disentangle what variables might be driving larger effects
A meta-analysis of 38 trials reported that intervention participants had a 1.94× greater probability of losing 5% of their initial weight vs control groups over 12-18 mo (RR, 1.94 [95% CI, 1.70 to 2.22]; 38 trials [n = 12,231]; I2 = 67.2%), which translated into an NNT of 8
|Few trials reported baseline cardiovascular risk status of participants
Very few trials reported differences in weight change at longer follow-up (eg, ≥2 y) or after a period of no intervention to examine maintenance of effects
Considerable statistical heterogeneity in all pooled analyses
No reporting bias suspected
|Moderate for benefit||Majority took place in United States in community-based or research settings
Few included primary care involvement
Interventions were highly variable in delivery mode but used similar behavior change strategies and messages
Most interventions were 1-2 y in duration, and more than one-third were group-based interventions
Half of trials represented an unselected population eligible for participation based on BMI; the remaining half recruited adults who were overweight or had obesity and at high cardiovascular risk (prediabetes, hypertension, high-normal blood pressure, the metabolic syndrome)
Median BMI, 33.4 across trials; median age, 50.3 yc
|Behavior-based weight loss maintenance||9 RCTs
|Pooled results of 8 trials indicated greater weight loss maintenance from behavior-based maintenance interventions vs control conditions at 12-18 mo (mean difference, −1.59 kg [3.5 lb] [95% CI, −2.38 to −0.79]; 8 trials [n = 1408]; I2 = 26.8%)
Eight of the 9 trials reported that both intervention and control participants regained weight over 12-18 mo of maintenance, with the intervention participants experiencing less weight regain; the remaining trial noted that both groups continued to lose weight, with no differences between groups
|Only 3 trials provided data beyond 18-mo follow-up
No reporting bias suspected
|Moderate for benefit||Design of trials was mixed, with some including a weight loss intervention for all participants within the trial (6 trials) and the others recruiting participants after documented or self-reported weight loss
Majority took place in United States in community-based or research settings, and few included primary care involvement; all but 1 of the trials represented a general, unselected population
Mean BMI at enrollment in weight loss phase, 34.2; median age, 49.2 yc
|Medication-based weight loss||20 RCTs
|Trials indicated greater weight loss from weight loss medications vs placebo at 12-18 mo (mean or LSM difference in weight change between medication and placebo ranged from −1.0 to −5.8 kg [2.2-12.8 lb]; no meta-analysis conducted)
Absolute changes in weight ranged from mean or LSM of −3.3 to −10.6 kg [7.3-23.4 lb] among medication participants and from −0.9 to −7.6 kg [2.0-16.8 lb] among placebo participants over 12-18 mo
Medication participants had a 1.2× to 3.9× greater probability of losing 5% of their initial weight vs placebo participants over 12-18 mo
|Trials generally had low follow-up (10 trials with ≥35% attrition) and most were of short duration (≤13-mo follow-up)
Limited data reporting (eg, only report LSMs, no between-group difference in mean change or variability around difference)
Very few trials reported differences in weight change at longer follow-up (eg, ≥2 y) or after a period of no intervention to examine maintenance of effects
No reporting bias suspected
|Low for benefit||One-half took place in the United States, with the majority occurring in academic, research, or specialty care settings
Few included primary care involvement; nearly one-half had run-in periods to assess medication adherence
Most interventions were 1-2 y in duration
Median BMI, 36.1; median age, 45 yc
|Medication-based weight loss maintenance||3 RCTs
|Trials indicate greater weight loss maintenance in medication vs placebo participants over 12 to 36 mo (mean difference ranged from −0.6 to −3.5; no meta-analysis conducted)
Absolute changes ranged from weight loss of 6.3 kg (14.0 lb) to gain of 5.1 kg (11.2 lb) among medication participants vs gain of 0.1 to 7.1 kg (0.2-15.7 lb) among placebo participants
|Trials generally had low follow-up (23%-30% attrition or NR) and were of short duration (2 trials of only 12- to 13-mo duration)
No reporting bias suspected
|Insufficient||All were conducted in research clinics in the United States, Canada, and Scandinavia
Participants were required to lose 5% to 8% of baseline weight before randomization
Median BMI at baseline, 35.6; median age, 46.2 yc
|KQ2: Intermediate Outcomes|
|Behavior-based weight loss||22 RCTs
|Incident diabetes (13 trials [n = 4095]): Absolute cumulative incidence of diabetes at up to 3-y follow-up ranged from 0%-15% in intervention and 0%-28.9% in control group
DPP and Finnish DPS found statistically significant lower incidence of developing diabetes at 3-9 y; no other trial found between-group differences, but trials generally had smaller sample sizes and shorter follow-up
Other intermediate outcomes: Prevalence of hypertension, the metabolic syndrome, use of CVD medications, and estimated 10-y risk of CVD were sparsely reported
Limited evidence from larger trials for reduced prevalence of hypertension and use of CVD medications; limited and mixed results for the metabolic syndrome and 10-y CVD risk
|Intermediate health outcomes were not well reported
Small size and short duration of many studies limited power to detect differences in intermediate outcomes in majority of studies
No reporting bias suspected
|Moderate for benefit (incident diabetes)
Low for benefit (other intermediate outcomes)
|All but 1 trial reporting incident diabetes were limited to adults with prediabetes|
|Behavior-based weight loss maintenance||0|
|Medication-based weight loss||6 RCTs
|Incident diabetes (3 trials [n = 9484]): Absolute cumulative incidence of diabetes at up to 4-y follow-up ranged from 0%-6% in medication and 1%-11% in placebo groups, which were statistically different for most drugs
Other intermediate outcomes: 4 trials reported mixed results for use of lipid-lowering and antihypertensive medications, prevalence of the metabolic syndrome, and 10-y CVD risk score
|Trials generally had high dropout rates
No reporting bias suspected
|Insufficient||21%-67% of participants had prediabetes|
|Medication-based weight loss maintenance||1 RCT
|Incident diabetes: Absolute cumulative incidence of diabetes at 3-y follow-up was 5% in medication and 11% in placebo groups, which was statistically different||NA (1 trial)||Only 1 trial with 35% dropout
No reporting bias suspected
|Insufficient||26% of participants had prediabetes|
|Behavior-based weight loss and weight loss maintenance||30 RCTs
|There were no serious harms related to the interventions, and most trials noted no differences between groups in the rates of adverse events, including cardiovascular events
In the 3 trials large enough to examine musculoskeletal issues between groups, results were mixed
|Harms sparsely reported for included trials
Few details provided about how harms were recorded and specific events that occurred
Did not include observational evidence on harms related to intentional weight loss
No reporting bias suspectede
|Low for harm||Applicable to US primary care population|
|Medication-based weight loss and weight loss maintenance||33 RCTs and 2 observational studies
|Serious adverse events were relatively uncommon and generally similar between groups
Participants randomized to medications experienced more adverse events, which was associated with higher dropout rates in the medication groups than in the placebo groups
|Few conducted statistical testing of differences between groups; harms listed on labels not well evaluated
No reporting bias suspected
|Moderate for harm||Highly selected group chosen for low risk of serious adverse events|
Abbreviations: BMI, body mass index; CVD, cardiovascular disease; DPP, Diabetes Prevention Program; DPS, Diabetes Prevention Study; LSM, least squares mean; NA, not applicable; NNT, number needed to treat; NR, not reported; QOL, quality of life; RCT, randomized clinical trial; RR, risk ratio.
a Consistency defined as the degree to which contributing studies estimate the same direction of effect (ie, consistently suggest benefit or harm). Consistency can be rated as reasonably consistent, inconsistent, or not applicable.
b Precision is defined as the degree to which contributing studies estimate the same magnitude of effect (ie, precisely suggest the magnitude of benefit or harm). Precision can be rated as reasonably precise, imprecise, or not applicable.
c BMI calculated as weight in kilograms divided by height in meters squared.
d Data for incident diabetes are consistent, but data for CVD are inconsistent.
e Suspected in 1 case for a behavior-based maintenance trial.