BACKGROUND:Racially and ethnically marginalized groups experience disproportionately high obesity rates, but are underrepresented in clinical trials of obesity treatments. Obesity treatments seem less effective for marginalized groups, but studies are characterized by small samples, clinic-based treatments, and little attention to socioeconomic position. We evaluated weight loss outcomes of a widely-available behavioral weight management program (Weight Watchers; WW) by race, ethnicity, income and education. METHODS:We performed an individual participant data meta-analysis of 11 WW intervention studies published from 2000-2025. T-tests compared weight loss between intervention and control participants within race, ethnicity, income and education subgroups. Among intervention participants, fixed effects multivariable regression estimated the odds of achieving a 5% weight loss across subgroups. RESULTS:Here we show that among 2972 participants (19% Non-Hispanic Black, 7% Hispanic/Latine; 30% <$50,000/y) and a mean (SD) weight of 96.2 (18.1) kg, WW interventions produce significantly greater weight loss than controls in all subgroups at 3, 6, and 12 months. Within the intervention group, Non-Hispanic Black participants are significantly less likely to experience a 5% weight loss than Non-Hispanic White participants at 3, 6, and 12 months, but there are no differences by income or education. CONCLUSIONS:A widely-available weight management program is more effective than controls for weight loss in all race, ethnicity, income, and education subgroups. However, the likelihood of clinically significant weight loss varies when comparing across racial and ethnic groups. These data can assist practitioners and patients when choosing evidence-based approaches to manage obesity among racially and ethnically marginalized groups.

OBJECTIVE:The objective of this study was to investigate the efficacy and safety of the Epitomee capsule versus placebo as an adjunct to high-intensity lifestyle intervention in participants with overweight or obesity. METHODS:The Randomized Evaluation of Efficacy and Safety of the Epitomee Capsule Trial (RESET) was a prospective, double-blind, placebo-controlled pivotal trial in adults with baseline BMI of 27.0 to 40.0 kg/m2. The co-primary endpoints at week 24 were percentage change from baseline in body weight for the Epitomee and placebo groups and proportion of Epitomee-treated patients achieving ≥5% weight loss compared with a 35% threshold. The primary safety endpoint was the incidence of device-related serious adverse events. RESULTS:A total of 138 participants received Epitomee and 141 received placebo. Mean (SD) change in body weight from baseline was -6.6% (6.5%) with Epitomee and -4.6% ( 4.7%) with placebo; least-squares means were -6.1% (0.6%) and -4.2% (0.6%), respectively (p = 0.0054). Fifty-six percent of Epitomee-treated participants attained ≥5% weight loss from baseline, which was significantly greater than the 35% predefined threshold (p < 0.0001). Twenty-seven percent of Epitomee-treated and eleven percent of placebo-treated participants achieved ≥10% weight loss. Adverse event rates were similar between the groups. No device-related serious adverse events occurred. CONCLUSIONS:The Epitomee capsule is a safe and efficacious nonpharmacological option for weight management with potential broad application in participants with overweight or obesity.

Early response (ER) to treatment is predictive of longer-term weight loss. In this post hoc analysis, ER to an oral shape-shifting superabsorbent hydrogel capsule (Epitomee) combined with a lifestyle intervention was compared to placebo combined with a lifestyle intervention. Participants (age = 48.5 ± 12.5 and 48.6 ± 12.4; BMI = 34.1 ± 3.3 and 33.7 ± 3.4, in the Epitomee and placebo groups, respectively) were randomised to Epitomee (N = 138) or placebo (N = 141) with lifestyle intervention. Analyses included body weight measurements taken at baseline, week 8, and week 24. Of the 279 participants enrolled in the study, 250 (90% of the ITT population) provided weight data, including 124 participants in the Epitomee group and 126 in the placebo group. Participants with missing weight data at week 24 were classified as non-responders. Early response (ER) was defined as a weight loss of ≥ 2% at week 8. Weight loss at week 24 was greater in ER to Epitomee compared to placebo (9.3% ± 6.0% vs. 6.9% ± 4.3%; p < 0.0001). The odds ratio for ER to achieve > 5% weight loss at week 24 was 4.10 (95% CI: 1.02, 16.46) for Epitomee and 2.38 (95% CI: 0.62, 9.21) for placebo. A greater proportion of ER to Epitomee, compared to placebo, achieved > 5% (76% vs. 62%; p = 0.0472), ≥ 7% (61% vs. 38%; p < 0.0045) and ≥ 10% (39% vs. 17%; p < 0.0025) weight loss at week 24. ER response to Epitomee was associated with greater weight loss at 24 weeks compared to placebo. Monitoring ER to Epitomee and titrating treatment based on ER may enhance weight loss.

To evaluate the impact of the Epitomee capsule on quality of life (QOL) and its association with weight loss in adults with overweight and obesity. This study analyzed the RESET double-blind, placebo-controlled results, focusing on predefined QOL endpoints and post hoc analyses. A total of 279 participants with a BMI of 27–40 kg/m² were treated for 24 weeks with Epitomee or placebo, along with lifestyle intervention. Statistical analyses examined changes in IWQOL-Lite-CT scores, their relationship with weight loss, and subgroup differences. Compared to the placebo group, the Epitomee group consistently showed improved outcomes in total IWQOL-Lite-CT score and Physical Function sub-score (p < 0.05), as well as numerically higher improvements in the Physical and Psychosocial sub-scores, although these did not reach statistical significance. Both treatment groups showed a significant improvement (p < 0.05) from baseline in the IWQOL-Lite-CT total score, as well as in Physical, Physical Function, and Psychosocial sub-scores over the 24-week period. A stronger correlation between weight loss and QOL improvements was observed with Epitomee vs. placebo. The Epitomee capsule, with lifestyle intervention, is associated with IWQOL-Lite-CT improvement, highlighting its potential as an effective non-pharmaceutical adjunct to lifestyle intervention for enhancing health outcomes in individuals with overweight and obesity.

Background:Management of obesity potentially improves cardiometabolic risk factors in patients with metabolic syndrome (MetS). The Epitomee capsule is a non-pharmacological, biodegradable device treatment for weight reduction in patients with overweight and obesity. Methods:This secondary analysis of the Randomized Evaluation of Safety and Efficacy of the Epitomee capsule Trial (RESET) (a randomized, 24-week, multicenter, placebo-controlled, double-blind trial that enrolled 279 adults aged ≥18 years with a BMI of 27-40 kg/m2) evaluated changes in cardiometabolic parameters in participants treated with Epitomee or placebo combined with lifestyle counseling among (a) the entire RESET study population, and (b) participants meeting diagnostic criteria for prediabetes. Predefined and exploratory endpoints included changes in waist circumference, glycemic parameters, blood pressure, and lipid blood levels; this analysis also assessed percent weight loss in participants with MetS. Results:Waist circumference, systolic and diastolic blood pressure and some measures of glycemia and lipids, improved with both Epitomee and placebo with no significant differences. Participants with prediabetes treated with Epitomee showed significantly greater reductions in HOMA-IR (p < 0.007) and insulin levels (p < 0.003) than the placebo group. Participants with MetS at baseline experienced significantly greater percent change in initial weight when treated with the Epitomee capsule (n = 27) compared to placebo (n = 31), -8.3% vs -5.2 %, respectively (p < 0.0004). Similar percentages of participants with MetS in both groups achieved ≥5 % weight reduction (59.3 % and 54.8 %, in Epitomee and placebo groups respectively). Significantly more participants with MetS treated with Epitomee achieved ≥10 % weight reduction compared with those treated with placebo (40.7 % vs. 6.5 %, respectively, p < 0.002). Conclusion:Treatment with either Epitomee and placebo combined with lifestyle improve cardiometabolic risk factors. Compared to placebo, Epitomee significantly reduced HOMA-IR and insulin levels in participants with prediabetes. Among participants with MetS, Epitomee significantly reduced body weight [ClinicalTrials.gov ID NCT04222322].

OBJECTIVE:The hormone peptide YY (PYY; cleaved into Y2-selective form PYY3-36) is an attractive candidate for use as a complementary pharmacotherapy for obesity along with glucagon-like peptide-1 (GLP-1) receptor agonists. This series of studies investigated a novel long-acting PYY3-36 analogue (PYY1875) alone and as an add-on to semaglutide for treatment of obesity. METHODS:Weight loss and food intake were first investigated in obese male rats, followed by phase 1 and 2 clinical studies investigating efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of PYY1875 as monotherapy and in combination with semaglutide in participants with overweight or obesity. RESULTS:PYY1875 induced additional body weight loss in semaglutide-treated obese rats. In the phase 1 study, all doses of PYY1875 alone and coadministered with semaglutide were tolerated. In the phase 2 study, a modest but not clinically meaningful treatment effect of PYY1875 1.0 mg versus placebo as an add-on to semaglutide 2.4 mg was observed. However, gastrointestinal-related adverse events were common with the 1.0-mg PYY1875 dose, and the 2.0-mg PYY1875 dose escalation regimen was not tolerated (both as add-ons to semaglutide). CONCLUSIONS:PYY1875 showed modest efficacy as an add-on to semaglutide for weight management in people with obesity, but the treatment was not well tolerated.

Introduction & Objective. The heterogeneity of type 2 diabetes (T2D) risk has a genetic basis that can be reflected in genetic risk scores (GRS). It is currently unknown if the nature of genetic risk for T2D varies with ancestral backgrounds. The aim of this study was to determine if patterns of genetic risk for T2D exist, and if they differ by ancestry in a sample of 342 Non-Hispanic White (NHW), Non-Hispanic Black (NHB), and Hispanic (HIS) adults with obesity and T2D. Methods: Participants were genotyped using the Infinium Global array with imputation. Six GRS representing distinct T2D pathophysiological pathways (beta-cell, proinsulin, obesity, lipodystrophy, liver/lipid, and insulin resistance (IR)) were calculated. Principal components analysis was performed on the GRS and genetic admixture values to identify ancestry-specific patterns for risk. Spearman correlations quantified strength and direction of associations of variables to each component. Participant self-reported ethnicity was used as a supplementary categorical variable. Results: Two principal components (PC) were retained. PC1 was associated with greater African ancestry (r=0.92, p <0.001) and the beta-cell and proinsulin GRS (r=0.442, p <0.001 and r=0.453, p<0.001, respectively). PC2 was associated with higher Native American ancestry (r=0.4691, p<0.001) and the IR and lipodystrophy GRS (r=0.52, p <0.001 and r=0.66, p<0.001, respectively). NHB were distinctly different from NHW for all variables. NHB had the highest scores for PC1, suggesting that genetic susceptibility to T2D in this group arises from impaired insulin secretion and processing abilities. HIS had the highest scores for PC2, which suggests T2D risk in this group is characterized by lipodystrophy-driven IR. Conclusion: Our results demonstrate that genetic risk for T2D manifests in patterns that are ancestry-specific. This may be useful in future research to help refine criteria for identifying at-risk individuals based on ancestral background. Disclosure L.A. Fowler: None. B. Gower: Advisory Panel; Cook Keto, Simply Good Foods, Abbott. J.R. Fernandez: None. P.M. O'Neil: Other Relationship; Novo Nordisk. Funding National Institutes of Health (T32HL105349); National Institutes of Health (T32DK062710)Clinical trial from which data were collected was sponsored by Weight Watchers International to the Medical University of South Carolina (NCT01601574)

Objective: Tobacco use and obesity are leading causes of preventable death in the U.S. E-cigarette use is on the rise; however, obesity prevalence among e-cigarette users is unknown. The present study characterized obesity prevalence among e-cigarette and tobacco users in a national sample of U.S. adults. Method: Data were obtained from the 2018 Behavioral Risk Factor Surveillance System. Approximately 249,726 participants provided data on e-cigarette and tobacco use, height, weight, and demographics, and were categorized as follows: Ever vaped, ever smoked; Ever vaped, never smoked; Never vaped, ever smoked; Never vaped, never smoked. Results: Obesity prevalence (BMI >= 30 kg/m2) differed significantly across groups: 33.0% (ever vaped, ever smoked); 27.7% (ever vaped, never smoked); 33.1% (never vaped, ever smoked); 32.1% (never vaped, never smoked), p < .001. Groups also differed demographically. Logistic regressions adjusted for demographics revealed subjects in the never vaped, ever smoked group were significantly more likely to have obesity relative to those in the never vaped, never smoked group (p < 0.001) with vaping status having no main effect. Secondary analyses using never smokers as the reference found current smokers were less likely to have obesity and former smokers were more likely to have obesity, p < .001. Discussion: The present study is the first to characterize U.S. obesity prevalence among e-cigarette and tobacco users. Obesity prevalence was lower in the ever vaped, never smoked group; however, this finding appears to be attributable to demographic variables. As e-cigarette use becomes more common, future research should examine the development and maintenance of obesity among users.

ObjectivesResearch on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health.Study DesignA survey research design with correlational analyses was used.MethodsA survey packet including the Community Culture Survey – Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes.Results1,930 participants from 49 US states (n = 1,592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant’s demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant’s age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants’ overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC’s measures of social vulnerability.ConclusionsNeighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

BACKGROUND:Type 2 diabetes (T2D) risk is higher among non-Hispanic black (NHB) and Hispanic individuals, for reasons that are unclear. AIMS:With this cross-sectional study, we tested the hypothesis that racial disparities in T2D prevalence can be partially traced to heterogeneity in etiology, as indicated by genetic subtypes that reflect distinct T2D phenotypes. METHODS:Using a diverse sample of 361 US adults with T2D (69.5% women; 34.1% NHB; 13.9% Hispanic), we derived genetic risk scores (GRS) representing five distinct T2D pathophysiological pathways from 94 loci: β-cell, proinsulin, obesity, lipodystrophy, and liver/lipid. Genetic predisposition for insulin resistance (IR) was also assessed using a 52-SNP IR risk score. RESULTS:The β-cell and proinsulin scores (as median [IQR]) were higher among NHB participants relative to NHW and Hispanics (β-cell GRS [NHB, 0.842(0.784-0.887) vs. NHW, 0.762(0.702-0.835) and Hispanic, 0.772(0.717-0.848)]); proinsulin GRS (NHB, 1.006[0.973-1.070] vs. NHW, 0.969[0.853-1.044] and Hispanic, 0.976[0.901-1.048]), whereas the liver/lipid and 52-SNP IR scores were higher in both NHB and Hispanic participants versus NHW (liver/lipid GRS [NHB, 1.09(0.78-1.18) and Hispanic, 0.895(0.736-1.227) vs. NHW, 0.794(0.666-1.157)]); 52-SNP IR GRS (NHB, 0.0095[0.009-0.010] and Hispanic, 0.0096 [0.0092-0.0101] vs. NHW, 0.0090[0.0084-0.0095]). CONCLUSIONS:Impaired β-cell function may underlie T2D etiology more profoundly in NHB, whereas hepatic dysfunction, lipid metabolism abnormalities, and genetic IR contribute to T2D etiology to a greater degree in both NHB and Hispanics. Further validation of these findings may form the basis for a personalized medicine approach to prevention and treatment of T2D.

ABSTRACT Introduction/Purpose Behaviorally based in-person multidisciplinary programs for weight loss have been studied for decades; however, delivery, scalability, and accessibility remain a challenge. We report pilot findings from a new asynchronous protocol-based telehealth weight loss program. Methods This 12-wk single-arm pilot study included adults (18–65 yr old) with body mass index (BMI) of 25–40 kg·m−2. The Home Weight Loss (HWL) program consisted of weekly app- and e-mail-delivered lesson modules covering traditional diet, exercise, and behavioral topics for weight loss. Daily weight and activity level were monitored automatically via a wireless scale and an activity tracker, and participants logged their caloric intake into the system. Monitoring data were reviewed weekly by clinicians who provided brief video-recorded feedback for participants to view at their convenience. Weight and height were measured in person at baseline and postintervention. Postintervention participants completed a satisfaction survey. Results Thirty participants (70% female; 80% White; mean age = 41 yr, standard deviation (SD) = 13.7 yr; mean BMI = 32.4 kg·m−2, SD = 4.3 kg·m−2) were enrolled, and 27 provided posttreatment data. Percent weight loss was 4.12% (SD = 4.22%). Overall, 93% of participants reported being satisfied with their overall experience in the program, and 59% cited individualized feedback as a benefit of the program. Conclusions The HWL program produced modest weight loss and demonstrated feasibility and participant acceptability. This model appears to be generally scalable for broader use and can be used to extend weight loss services for those not residing near medical centers and those in need of asynchronous and virtual feedback.

KEYWORDS: Semaglutide 2.4 mgobesityweight managementprimary carecardiometabolicquality of lifebest-practices

Importance Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management. Objective To compare the efficacy and adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily subcutaneous liraglutide, 3.0 mg (both with diet and physical activity), in people with overweight or obesity. Design, Setting, and Participants Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: September 11-November 26) to May 2021 (end of follow-up: May 11) in adults with body mass index of 30 or greater or 27 or greater with 1 or more weight-related comorbidities, without diabetes (N = 338). Interventions Participants were randomized (3:1:3:1) to receive once-weekly subcutaneous semaglutide, 2.4 mg (16-week escalation; n = 126), or matching placebo, or once-daily subcutaneous liraglutide, 3.0 mg (4-week escalation; n = 127), or matching placebo, plus diet and physical activity. Participants unable to tolerate 2.4 mg of semaglutide could receive 1.7 mg; participants unable to tolerate 3.0 mg of liraglutide discontinued treatment and could restart the 4-week titration. Placebo groups were pooled (n = 85). Main Outcomes and Measures The primary end point was percentage change in body weight, and confirmatory secondary end points were achievement of 10% or more, 15% or more, and 20% or more weight loss, assessed for semaglutide vs liraglutide at week 68. Semaglutide vs liraglutide comparisons were open-label, with active treatment groups double-blinded against matched placebo groups. Comparisons of active treatments vs pooled placebo were supportive secondary end points. Results Of 338 randomized participants (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean [SD] body weight, 104.5 [23.8] kg; mean [SD] body mass index, 37.5 [6.8]), 319 (94.4%) completed the trial, and 271 (80.2%) completed treatment. The mean weight change from baseline was -15.8% with semaglutide vs -6.4% with liraglutide (difference, -9.4 percentage points [95% CI, -12.0 to -6.8]; P < .001); weight change with pooled placebo was -1.9%. Participants had significantly greater odds of achieving 10% or more, 15% or more, and 20% or more weight loss with semaglutide vs liraglutide (70.9% of participants vs 25.6% [odds ratio, 6.3 {95% CI, 3.5 to 11.2}], 55.6% vs 12.0% [odds ratio, 7.9 {95% CI, 4.1 to 15.4}], and 38.5% vs 6.0% [odds ratio, 8.2 {95% CI, 3.5 to 19.1}], respectively; all P < .001). Proportions of participants discontinuing treatment for any reason were 13.5% with semaglutide and 27.6% with liraglutide. Gastrointestinal adverse events were reported by 84.1% with semaglutide and 82.7% with liraglutide. Conclusions and Relevance Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks. Trial Registration ClinicalTrials.gov Identifier: NCT04074161.

Obesity is increasingly recognised as a chronic, relapsing disease. Lost weight is very frequently reclaimed, despite scores of trials of potential methods for improving maintenance. These trials typically include intensive lifestyle change, weight loss and maintenance interventions offered in professional settings, and follow-up assessment periods usually not exceeding 2 years.

Obesity negatively impacts patients' health-related quality of life (QOL) and is associated with a range of complications such as type 2 diabetes (T2D), cardiovascular disease, and sleep apnea, alongside decreased physical function, mobility, and control of eating. The Semaglutide Treatment Effect in People with obesity (STEP) trials compared once-weekly subcutaneous semaglutide 2.4 mg with placebo in adults with overweight or obesity, with or without T2D. This article reviews the effects of semaglutide 2.4 mg on QOL, control of eating, and body composition. Weight-related QOL was assessed using the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), and health-related QOL was assessed with the 36-item Short Form Health Survey version 2 (SF-36v2®). Control of eating was evaluated using the Control of Eating questionnaire in a subgroup of participants in one trial. Body composition was evaluated via dual-energy x-ray absorptiometry in another trial, in a subgroup of participants with a body mass index of ≤40 kg/m2. All IWQOL-Lite-CT scores (Physical Function, Physical, Psychosocial, and Total Score) improved with semaglutide 2.4 mg significantly more than with placebo. Across the trials, changes in SF-36v2 scores were generally in favor of semaglutide versus placebo. There were significant improvements in all Control of Eating questionnaire domains (craving control, craving for savory, craving for sweet, and positive mood) up to week 52 with semaglutide treatment versus placebo, with improvements in craving control and craving for savory remaining significantly different at week 104. Body composition findings showed that reductions in total fat mass were greater with semaglutide versus placebo. These findings highlight the wider benefits that patients can experience with once-weekly subcutaneous semaglutide 2.4 mg, in addition to weight loss, including improvements in patients' wellbeing and ability to perform daily activities. Taken together, these are important considerations for primary care when incorporating pharmacotherapy for weight management.

Importance:Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches. Objective:To compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity. Design, Setting, and Participants:Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (N = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30). Interventions:Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. Main Outcomes and Measures:The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight. Results:Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was -16.0% for semaglutide vs -5.7% for placebo (difference, -10.3 percentage points [95% CI, -12.0 to -8.6]; P < .001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P < .001). A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively; P < .001). Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%). Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants. Conclusions and Relevance:Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings. Trial Registration:ClinicalTrials.gov Identifier: NCT03611582.