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This paper describes the baseline characteristics of the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) study, one of the largest cardiovascular (CV) outcome studies in the field of obesity, which evaluates the effect of semaglutide versus placebo on major CV events.SELECT enrolled individuals with overweight or obesity without diabetes, with prior myocardial infarction, stroke, and/or peripheral artery disease. This study reports participants' baseline characteristics in the full study population and subgroups defined by baseline glycated hemoglobin (HbAThe study enrolled 17,605 participants (72.5% male) with an average (SD) age of 61.6 (8.9) years and BMI of 33.34 (5.04) kg/mThe enrolled population in SELECT includes participants across a broad range of relevant risk categories. This will allow the study to garner information about the CV benefits of semaglutide across these relevant clinical subgroups.

OBJECTIVE The objective of this study was to develop a simple and practical guide for discussing and managing obesity in primary care settings. METHODS This study convened representatives from 12 primary care and obesity specialty organizations for a series of roundtable meetings to discuss the key components of obesity treatment in primary care. Attendees identified the need for a guide for primary care providers that outlined the key steps for discussing obesity with patients and managing their care while recognizing the significant time constraints on such provider/patient encounters. RESULTS Prevailing themes from the roundtable sessions suggested that the key components of addressing obesity in primary care settings are obtaining patient permission, addressing weight bias, providing a diagnosis, and emphasizing shared decision-making. A modified "6A" framework with the steps "Ask," "Assess," "Advise," "Agree," "Assist," and "Arrange" was deemed appropriate to organize the process of weight management in primary care. An algorithm was developed to provide a script for the patient/provider encounter. CONCLUSIONS The expert panel developed a short, accessible, practical, and informative guide for obesity management by primary care clinicians. Efforts are under way to disseminate the guide to primary care providers through the 11 participating organizations that have endorsed it.

Objective This study aimed to determine the medical cost impact and return on investment (ROI) of a large, commercial, digital, weight-management intensive lifestyle intervention (ILI) program (Real Appeal). Methods Participants in this program were compared with a control group matched by age, sex, geographic region, health risk, baseline medical costs, and chronic conditions. Medical costs were defined as the total amount paid for all medical expenses, inclusive of both the insurers' and the study participants' responsibility. Results In the 3 years following program registration, the intent-to-treat (ITT) cohort had significantly lower medical expenditures than the matched controls, with an average of -$771 or 12% lower costs (P = 0.002). Among 4,790 ITT participants, a total savings of $3,693,090 compared with total program costs of $1,639,961 translated into a 2.3:1 ROI. Program completers (n = 3,990), who attended more sessions than the overall ITT group, had greater mean weight loss (-4.4%), greater cost savings (-$956 or 14%), and an ROI of 2.0:1 over the 3-year time frame compared with matched controls. Conclusions The findings demonstrated that the digital weight-management ILI was associated with a significantly positive ROI. Employers and payers willing to cover the cost of an ILI that produces both weight loss and demonstrated cost benefits can improve health and save money for their population with overweight or obesity.

Against the backdrop of obesity as a major public health problem, we examined three questions: How much weight loss is needed to benefit patients with obesity? How well do current therapies do in producing weight loss? What strategies can be used to improve patient outcomes using evidence-based studies. This paper reviews literature on the outcomes of lifestyle, diet, medications and surgical treatments for obesity using literature searches for obesity treatments. Current treatments, including lifestyle, diet and exercise, produce a weight loss of 5% to 7% on average. Despite continued attempts to identify superior dietary approaches, most careful comparisons find that low carbohydrate diets are not significantly better than low fat diets for weight loss. The four medications currently approved by the US Food and Drug Administration for long-term management of obesity are not as effective as surgery, adding about 5% on average to lifestyle approaches to weight loss. Two new medications that are under investigation, semaglutide and tirzepatide, significantly improve on this. For all treatments for weight loss, including lifestyle, medications and surgery, there is enormous variability in the amount of weight lost. Examination of this literature has yielded evidence supporting baseline and process predictors, but the effect sizes associated with these predictors are small and there are no prospective studies showing that a personalized approach based on genotype or phenotype will yield uniform success. Because obesity is a chronic disease it requires a 'continuous treatment model' across the lifespan.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality. Although it has been widely appreciated that obesity is a major risk factor for CVD, treatments that produce effective, durable weight loss and the impact of weight reduction in reducing cardiovascular risk have been elusive. Instead, progress in CVD risk reduction has been achieved through medications indicated for controlling lipids, hyperglycemia, blood pressure, heart failure, inflammation, and/or thrombosis. Obesity has been implicated as promoting all these issues, suggesting that sustained, effective weight loss may have independent cardiovascular benefit. GLP-1 receptor agonists (RAs) reduce weight, improve glycemia, decrease cardiovascular events in those with diabetes, and may have additional cardioprotective effects. The GLP-1 RA semaglutide is in phase 3 studies as a medication for obesity treatment at a dose of 2.4 mg subcutaneously (s.c.) once weekly. Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) is a randomized, double-blind, parallel-group trial testing if semaglutide 2.4 mg subcutaneously once weekly is superior to placebo when added to standard of care for preventing major adverse cardiovascular events in patients with established CVD and overweight or obesity but without diabetes. SELECT is the first cardiovascular outcomes trial to evaluate superiority in major adverse cardiovascular events reduction for an antiobesity medication in such a population. As such, SELECT has the potential for advancing new approaches to CVD risk reduction while targeting obesity.

Objective This study was designed to determine whether intensive lifestyle intervention (ILI) aimed at weight loss lowers cancer incidence and mortality. Methods Data from the Look AHEAD trial were examined to investigate whether participants randomized to ILI designed for weight loss would have reduced overall cancer incidence, obesity-related cancer incidence, and cancer mortality, as compared with the diabetes support and education (DSE) comparison group. This analysis included 4,859 participants without a cancer diagnosis at baseline except for nonmelanoma skin cancer. Results After a median follow-up of 11 years, 684 participants (332 in ILI and 352 in DSE) were diagnosed with cancer. The incidence rates of obesity-related cancers were 6.1 and 7.3 per 1,000 person-years in ILI and DSE, respectively, with a hazard ratio (HR) of 0.84 (95% CI: 0.68-1.04). There was no significant difference between the two groups in total cancer incidence (HR, 0.93; 95% CI: 0.80-1.08), incidence of nonobesity-related cancers (HR, 1.02; 95% CI: 0.83-1.27), or total cancer mortality (HR, 0.92; 95% CI: 0.68-1.25). Conclusions An ILI aimed at weight loss lowered incidence of obesity-related cancers by 16% in adults with overweight or obesity and type 2 diabetes. The study sample size likely lacked power to determine effect sizes of this magnitude and smaller.

Diabetes remission—the occurrence of durable normoglycemia without antidiabetic medications—has been demonstrated in some patients with type 2 diabetes who have achieved and sustained weight loss through lifestyle intervention or metabolic and bariatric surgery. Although this pursuit would represent a paradigm shift in our diabetes chronic care model, could diabetes remission become a routine treatment strategy in patients with type 2 diabetes? This article reviews the mechanisms by which weight loss can drive improvements in insulin sensitivity and β-cell function sufficient to normalize glycemia, treatment approaches that provide evidence for diabetes remission, and avenues for developing the research and discovery that will be required to make diabetes remission possible as part of the routine medical management of type 2 diabetes.

A recent Perspective article described the “carbohydrate-insulin model (CIM)” of obesity, asserting that it “better reflects knowledge on the biology of weight control” as compared with what was described as the “dominant energy balance model (EBM),” which fails to consider “biological mechanisms that promote weight gain.” Unfortunately, the Perspective conflated and confused the principle of energy balance, a law of physics that is agnostic as to obesity mechanisms, with the EBM as a theoretical model of obesity that is firmly based on biology. In doing so, the authors presented a false choice between the CIM and a caricature of the EBM that does not reflect modern obesity science. Here, we present a more accurate description of the EBM where the brain is the primary organ responsible for body weight regulation operating mainly below our conscious awareness via complex endocrine, metabolic, and nervous system signals to control food intake in response to the body's dynamic energy needs as well as environmental influences. We also describe the recent history of the CIM and show how the latest “most comprehensive formulation” abandons a formerly central feature that required fat accumulation in adipose tissue to be the primary driver of positive energy balance. As such, the new CIM can be considered a special case of the more comprehensive EBM but with a narrower focus on diets high in glycemic load as the primary factor responsible for common obesity. We review data from a wide variety of studies that address the validity of each model and demonstrate that the EBM is a more robust theory of obesity than the CIM.

New appetite-regulating antiobesity treatments such as semaglutide and agents under investigation such as tirzepatide show promise in achieving weight loss of 15% or more. Energy expenditure, fat oxidation, and lean mass preservation are important determinants of weight loss and weight-loss maintenance beyond appetite regulation. This review discusses prior failures in clinical development of weight-loss drugs targeting energy expenditure and explores novel strategies for targeting energy expenditure: mitochondrial proton leak, uncoupling, dynamics, and biogenesis; futile calcium and substrate cycling; leptin for weight maintenance; increased sympathetic nervous system activity; and browning of white fat. Relevant targets for preserving lean mass are also reviewed: growth hormone, activin type II receptor inhibition, and urocortin 2 and 3. We endorse moderate modulation of energy expenditure and preservation of lean mass in combination with efficient appetite reduction as a means of obtaining a significant, safe, and long-lasting weight loss. Furthermore, we suggest that the regulatory guidelines should be revisited to focus more on the quality of weight loss and its maintenance rather than the absolute weight loss. Commitment to this research focus both from a scientific and from a regulatory point of view could signal the beginning of the next era in obesity therapies.

OBJECTIVE Patients with type 2 diabetes are encouraged to lose weight, but excessive weight loss in older adults may be a marker of poor health and subsequent mortality. We examined weight change during the postintervention period of Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) with diabetes support and education (DSE) (control) in overweight/obese individuals with type 2 diabetes and sought to identify predictors of excessive postintervention weight loss and its association with mortality. RESEARCH DESIGN AND METHODS These secondary analyses compared postintervention weight change (year 8 to final visit; median 16 years) in ILI and DSE in 3,999 Look AHEAD participants. Using empirically derived trajectory categories, we compared four subgroups: weight gainers (n = 307), weight stable (n = 1,561), steady losers (n = 1,731), and steep losers (n = 380), on postintervention mortality, demographic variables, and health status at randomization and year 8. RESULTS Postintervention weight change averaged −3.7 ± 9.5%, with greater weight loss in the DSE than the ILI group. The steep weight loss trajectory subgroup lost on average 17.7 ± 6.6%; 30% of steep losers died during postintervention follow-up versus 10–18% in other trajectories (P < 0001). The following variables distinguished steep losers from weight stable: baseline, older, longer diabetes duration, higher BMI, and greater multimorbidity; intervention, randomization to control group and less weight loss in years 1–8; and year 8, higher prevalence of frailty, multimorbidity, and depressive symptoms and lower use of weight control strategies. CONCLUSIONS Steep weight loss postintervention was associated with increased risk of mortality. Older individuals with longer duration of diabetes and multimorbidity should be monitored for excessive unintentional weight loss.

OBJECTIVE: Look AHEAD, a randomized trial comparing intensive lifestyle intervention (ILI) and diabetes support and education (DSE) (control) in 5,145 individuals with overweight/obesity and type 2 diabetes, found no significant differences in all-cause or cardiovascular mortality or morbidity during 9.6 (median) years of intervention. Participants in ILI who lost ≥10% at 1 year had lower risk of composite cardiovascular outcomes relative to DSE. Since effects of ILI may take many years to emerge, we conducted intent-to-treat analyses comparing mortality in ILI over 16.7 years (9.6 years of intervention and then observation) to DSE. In a secondary exploratory analysis, we compared mortality by magnitude of weight loss in ILI relative to DSE. RESEARCH DESIGN AND METHODS: Primary outcome was all-cause mortality from randomization to 16.7 years. Other outcomes included cause-specific mortality, interactions by subgroups (age, sex, race/ethnicity, and cardiovascular disease history), and an exploratory analysis by magnitude of weight loss in ILI versus DSE as reference. Analyses used proportional hazards regression and likelihood ratio. RESULTS: The incidence of all-cause mortality did not differ significantly in ILI and DSE (549 and 589 participants, respectively) (hazard ratio [HR] 0.91 [95% CI 0.81, 1.02]; P = 0.11). There were no significant differences between treatments in cause-specific mortality or within prespecified subgroups. ILI participants who lost ≥10% at 1 year had a 21% reduced risk of mortality (HR 0.79 [95% CI 0.67, 0.94]; P = 0.007) relative to DSE. CONCLUSIONS: ILI focused on weight loss did not significantly affect mortality risk. However, ILI participants who lost ≥10% had reduced mortality relative to DSE.

Objective To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomized 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education. Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for prespecified baseline CVD history subgroups (interaction P = 0.063). Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]). Methods This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalization for angina, as well as three secondary composite cardiovascular outcomes. Results Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035). This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events. In those with a CVD history, statin use was high and similar by group. In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group. Conclusions Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design.

An analysis of the STEP 2 trial evaluated the effect of s.c. semaglutide 2.4 mg vs. placebo (PBO) on physical function (PF) in adults with overweight/obesity and type 2 diabetes (T2D). The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; data not shown), or PBO (N=403), plus lifestyle changes. Endpoints included change in PF (baseline-week 68) using the SF-36v2® Health Survey acute version (SF-36) and Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQoL-Lite-CT), and achievement of meaningful within-person PF improvements (≥3.7 points [SF‑36]; ≥14.6 points [IWQoL-Lite-CT]). Patients were 51% female, with a mean age of 55 years, body weight 99.8 kg, and BMI 35.7 kg/m2. Body weight change at week 68 with semaglutide 2.4 mg vs. PBO was -9.6% vs. -3.4%. Semaglutide significantly improved PF vs. PBO on SF-36 and IWQoL‑Lite‑CT (Table). SF-36 and IWQoL-Lite-CT PF improvements correlated with weight loss during the trial. Proportions of patients with clinically meaningful PF improvements were greater with semaglutide vs. PBO (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved PF vs. PBO, and led to greater proportions of patients with clinically meaningful PF changes in SF-36 and IWQoL-Lite-CT. Disclosure S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. T. Kalayci oral: Employee; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S

Effects of s.c. semaglutide 2.4 mg vs. placebo on health-related quality of life (HRQoL) were evaluated in the STEP 2 trial in adults with overweight/obesity and T2D. The STEP 2 trial was an RCT in adults with BMI ≥27 kg/m2 and T2D (NCT03552757). Patients were randomized 1:1:1 to 68 weeks’ once-weekly semaglutide 2.4 mg (N=404), 1.0 mg (N=403; results not shown), or placebo (N=403), plus lifestyle intervention. Changes in scores at week 68, and achievement of clinically meaningful within-person improvements (see Table for meaningful change thresholds), in weight-related QoL (Impact of Weight on Quality of Life-Lite Clinical Trials Version [IWQoL-Lite-CT]) and HRQoL (SF-36v2® Health Survey acute version [SF-36]) were assessed. Body weight change at week 68 with semaglutide 2.4 mg vs. placebo was -9.6% vs. -3.4%. Changes in IWQoL-Lite-CT scores and SF-36 scores (except role-emotional) were consistently in favor of semaglutide vs. placebo (Table). The proportions of patients with clinically meaningful improvements was greater with semaglutide vs. placebo for all IWQoL-Lite-CT scores and SF-36 physical functioning score (Table). In adults with overweight/obesity and T2D, semaglutide 2.4 mg improved both physical and mental health components vs. placebo and led to greater proportions of patients with clinically meaningful changes in weight-related QoL and physical functioning. Disclosure D. Rubino: Advisory Panel; Self; Novo Nordisk, Other Relationship; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Speaker’s Bureau; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. L. Faerch: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. H. H. Meincke: Employee; Self; Novo Nordisk A/S. R. F. Kushner: Advisory Panel; Self; Novo Nordisk A/S. S. Pedersen: Advisory Panel; Self; AstraZeneca, Bausch and Lomb Incorporated, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Global Services, LLC., Novo Nordisk, Consultant; Self; Abbott, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Speaker’s Bureau; Self; Abbott Laboratories, AstraZeneca, Bausch and Lomb Incorporated, Bayer Inc., Boehringer Ingelheim (Canada) Ltd., Dexcom, Inc., Eli Lilly and Company, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi. D. H. Ryan: Advisory Panel; Self; Alyvent, Naturally Slim, Epitommee,, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Global Services, LLC., Pfizer Inc., Redesign Health, Inc., Sanofi, Consultant; Self; Bausch Health, Canada, Phenomix, Xeno Bioscience, Gila Therapeutics, Scientific Intake, UnitedHealth Group, Other Relationship; Self; Novo Nordisk Inc. S. Wharton: Advisory Panel; Self; Novo Nordisk A/S, Novo Nordisk Canada Inc., Speaker’s Bureau; Self; AstraZeneca, Bausch Health, Canada, Novo Nordisk, Novo Nordisk Canada Inc. N. Zeuthen: Employee; Self; Novo Nordisk, Stock/Shareholder; Self; Novo Nordisk. R. Kolotkin: Consultant; Self; Novo Nordisk, Other Relationship; Self; Rhythm Pharmaceuticals, Inc. Funding Novo Nordisk A/S

Older medications approved for chronic weight management (orlistat, naltrexone/bupropion, liraglutide 3 mg and, in the USA, phentermine/topiramate) have not been widely adopted by health care providers. Those medications produce only modest additional weight loss when used to augment lifestyle intervention. However, semaglutide 2.4 mg weekly has recently emerged and produces much more weight loss - on average 15% weight loss at 1 year. Semaglutide's enhanced efficacy and that its class (GLP-1 receptor analogs) is well-known may result in more clinicians adopting pharmacotherapy. Furthermore, the first dedicated cardiovascular outcome trial powered for superiority testing an anti-obesity medication (SELECT) is underway with semaglutide 2.4 mg. A positive outcome will further promote the concept that weight management should be a primary target for cardiometabolic disease control. In phase 3, tirzepatide and cagrilintide/semaglutide combination are showing promise for even greater weight loss efficacy. Another recently approved medication takes a personalized medicine approach; setmelanotide is approved as a therapy for those with some of the ultra-rare genetic diseases characterized by severe, early onset obesity. This chapter reviews the currently available and anticipated medications for chronic weight management as well as those approved for the genetic and syndromic obesities.

International audience; This review details the proceedings of a Pennington Biomedical scientific symposium titled, "What Should I Eat and Why? The Environmental, Genetic, and Behavioral Determinants of Food Choice." The symposium was designed to review the literature about energy homeostasis, particularly related to food choice and feeding behaviors, from psychology to physiology. This review discusses the intrinsic determinants of food choice, including biological mechanisms (genetics), peripheral and central signals, brain correlates, and the potential role of the microbiome. This review also address the extrinsic determinants (environment) of food choice within our physical and social environments. Finally, this review reports the current treatment practices for the clinical management of eating-induced overweight and obesity. An improved understanding of these determinants will inform best practices for the clinical treatment and prevention of obesity. Strategies paired with systemic shifts in our public health policies and changes in our "obesogenic" environment will be most effective at attenuating the obesity epidemic.

Objective Given the disease burden and economic costs of obesity in the United States, scalable approaches to weight loss and weight management are needed. This study evaluated self-reported weight-loss outcomes associated with a commercial intensive lifestyle intervention marketed to employers and delivered electronically to employees. Methods Data were collected for participants who enrolled in an online intensive lifestyle intervention weight-loss program from July 2015 through June 2016. An intent-to-treat analysis of participants who attended at least one session is reported. Results Ninety-six companies, with approximately 437,215 eligible adult beneficiaries, launched Real Appeal in July 2015. In the first 12 months of the program, 69,598 adults enrolled and 87% met at-risk criteria for prediabetes, diabetes, or cardiovascular disease. The intent-to-treat cohort (n = 52,461), all of whom attended at least one session, lost an average of 2.8% body weight, with 23% achieving 5% or more weight loss. Active participants (n = 38,836) lost an average of 3.5% body weight, with 29% achieving 5% weight loss. Program completers (n = 27,164) lost an average of 4.3% body weight, with 36% of the cohort achieving 5% weight loss. Conclusions This study demonstrated that an employer-offered, online, behavioral weight-loss program was an effective, scalable solution for engaging more than 50,000 participants with overweight and obesity.

Background Individual variability in response to multiple modalities of obesity treatment is well documented, yet our understanding of why some individuals respond while others do not is limited. The etiology of this variability is multifactorial; however, at present, we lack a comprehensive evidence base to identify which factors or combination of factors influence treatment response. Objectives This paper provides an overview and rationale of the Accumulating Data to Optimally Predict obesity Treatment (ADOPT) Core Measures Project, which aims to advance the understanding of individual variability in response to adult obesity treatment. This project provides an integrated model for how factors in the behavioral, biological, environmental, and psychosocial domains may influence obesity treatment responses and identify a core set of measures to be used consistently across adult weight-loss trials. This paper provides the foundation for four companion papers that describe the core measures in detail. Significance The accumulation of data on factors across the four ADOPT domains can inform the design and delivery of effective, tailored obesity treatments. ADOPT provides a framework for how obesity researchers can collectively generate this evidence base and is a first step in an ongoing process that can be refined as the science advances.

The prevalence of obesity, measured by body mass index, has risen to unacceptable levels in both men and women in the United States and worldwide with resultant hazardous health implications. Genetic, environmental, and behavioral factors influence the development of obesity, and both the general public and health professionals stigmatize those who suffer from the disease. Obesity is associated with and contributes to a shortened life span, type 2 diabetes mellitus, cardiovascular disease, some cancers, kidney disease, obstructive sleep apnea, gout, osteoarthritis, and hepatobiliary disease, among others. Weight loss reduces all of these diseases in a dose-related manner—the more weight lost, the better the outcome. The phenotype of “medically healthy obesity” appears to be a transient state that progresses over time to an unhealthy phenotype, especially in children and adolescents. Weight loss is best achieved by reducing energy intake and increasing energy expenditure. Programs that are effective for weight loss include peer-reviewed and approved lifestyle modification programs, diets, commercial weight-loss programs, exercise programs, medications, and surgery. Over-the-counter herbal preparations that some patients use to treat obesity have limited, if any, data documenting their efficacy or safety, and there are few regulatory requirements. Weight regain is expected in all patients, especially when treatment is discontinued. When making treatment decisions, clinicians should consider body fat distribution and individual health risks in addition to body mass index.

Objective Minimal risk weight loss tools are needed. This study's objective was to confirm Food and Drug Administration submissions of the SmartByte™ System's safety and efficacy. Methods This 16-week, prospective, single-arm, four-centre, observational study assessed the oral device in combination with a video-delivered lifestyle programme in adults aged 18-49 years with body mass index 27 to

Summary To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24-h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m−2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (−4.4 kg [95% CI: −5.9, −3.0]) than for women in the lowest carbohydrate group (−1.8 kg [95% CI: −3.2, −0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow-up protein intake was associated with greater weight loss, consistent with the ‘protein spread theory’. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months.

While the first reported case of SARS-CoV-2 occurred in Wuhan, China, in December 2019, giving the name to the disease COVID-19, the World Health Organization declared this a Public Health Emergency of International Concern on January 30, 2020, and a pandemic on March 11, 2020 Persons with obesity indeed have increased rates of comorbid conditions, often have impaired immune responses to viral threats and abnormal proinflammatory and prothrombotic profiles, and experience stigma in health care settings where they are at a disadvantage because of their size (limited use of diagnostic equipment and therapeutic maneuvers), all factors driving COVID-19 complications and mortality (1) [ ]the annual Obesity Journal Symposium was held virtually at ObesityWeek with an outstanding and diverse group of papers and young scientists presenting their work

People with obesity commonly face a pervasive, resilient form of social stigma. They are often subject to discrimination in the workplace as well as in educational and healthcare settings. Research indicates that weight stigma can cause physical and psychological harm, and that affected individuals are less likely to receive adequate care. For these reasons, weight stigma damages health, undermines human and social rights, and is unacceptable in modern societies. To inform healthcare professionals, policymakers, and the public about this issue, a multidisciplinary group of international experts, including representatives of scientific organizations, reviewed available evidence on the causes and harms of weight stigma and, using a modified Delphi process, developed a joint consensus statement with recommendations to eliminate weight bias. Academic institutions, professional organizations, media, public-health authorities, and governments should encourage education about weight stigma to facilitate a new public narrative about obesity, coherent with modern scientific knowledge.

Summary It may at times seem like we are searching for a cure for obesity with a magic diet, evidenced by past fad diets and the current attraction to low-carbohydrate diets and ketogenic diets. This chapter discusses the biologic basis of our eating behaviors and the biologic basis of health improvement with weight loss. With this understanding, we discuss the behavioral change approaches that can be used to navigate the modern food environment and lose enough weight to improve health. First, we review the evidence base for lifestyle intervention with a purpose of understanding the push by all professional societies to implement intensive behavioral therapy for obesity. The chapter discusses calorie targets and calorie deficits, episodic fasting, mindfulness, and the emergence of electronic self-monitoring tools. All of these approaches are based on our understanding of the biology of food intake. But weight loss is only the beginning; the hard part of losing weight for most patients with obesity is weight loss maintenance, and we discuss the important shift in focus to maintain lost weight, along with promising methods to achieve this goal.

IMPACT: By demonstrating the feasibility of a multimodal, interdisciplinary intervention for prediabetes, the current project aims to provide a template for the prevention of diabetes and associate comorbid conditions. OBJECTIVES/GOALS: To determine if a multi-modal, interdisciplinary intervention delivered to a group of prediabetic patients will result in reduced rates of diabetes progression. This project is a retrospective evaluation that will exam the feasibility and possibly efficacy of this intervention. METHODS/STUDY POPULATION: We will enroll 50 participants for the clinic, aged 21-60 inclusive. Patients will have a Body Mass Index >27kg/m2 with a diagnosis of prediabetes. Patients must be non-pregnant, using approved contraception, and agree to not become pregnant for 1 year after enrollment. After enrollment, the initial treatment period is for 1 year and includes a 12 week low calorie diet plan, a 6-month intensive behavioral and lifestyle modification plan followed by a 6 month behavior reinforcement extension. Weight management medications may be used if appropriate for the patient from a clinical perspective during the 6-month intensive behavioral/lifestyle modification. RESULTS/ANTICIPATED RESULTS: It is anticipated that there will be decreased weight with a mean weight loss goal of approximately >10%. Furthermore, it is expect that there will be improvement of other markers of metabolic disease. These include improvement of lipid values (LDL-C, HDL-C, Triglycerides, Total Cholesterol) as well as blood pressure with expected blood pressures of below 130/80 in greater than 50% of participants. Finally, It is expected that 50% or greater participants will have improvement of glycemic control. It is anticipated that greater than 50% of participants will have improvement of glycemic control and achieve normoglycemia. These values will be determined based upon fasting glucose or A1c. DISCUSSION/SIGNIFICANCE OF FINDINGS: The significance of this intervention is enormous. By demonstrating feasibility in this trial, we can work toward both assessing efficacy and possibly dissemination of this model program. If these interventions provide durable changes at scale, this could help slow the epidemic of obesity and obesity related comorbid conditions.

This article addresses current best practices in obesity management, primarily through the discussion of 5 guidelines documents: those sponsored by the US National Institutes of Health and the AHA/ACC/TOS, ENDO, ASBP, AACE, and the United Kingdom's NICE. Common to all of these reports is the emphasis on addressing weight management as a pathway to prevention and optimal management of obesity-associated comorbidities (ie, type 2 diabetes and cardiovascular diseases). No one of these documents fits all needs; all have a place. Further, no one of these documents is final. As knowledge advances, all will require updating.

George as a child. Who would have known then the impact he would make on the world of the science of obesity? George at the end of his tenure as executive director of Pennington Biomedical Research Center. As Mitzi watches, George receives a commemorative plaque from Dr. Claude Bouchard (executive director after George) during a 20th anniversary celebration event for Pennington Biomedical Research Center. In gratitude and acknowledgment for his work and contributions, and for always doing things the “George Bray way,” Pennington Biomedical named the walkway between the basic and clinical research buildings Bray’s “Weigh” in his honor on the occasion of his retirement from the center on 10 December 2014. George A. Bray was born 25 July 1931 in Winnetka, IL, during the peak of the Depression. He was the first child of George August and Mary H. Bray. His only sibling, Mary Elizabeth (Betsy) Bray, died secondary to rheumatic heart disease. Influenced by his mother, George developed a natural interest in education at a young age, even though one of his teachers at Hubbard Woods School in Winnetka reported that 11-year-old “George is doing good average work in all subjects” (1). Despite this inauspicious assessment, high school marked the emergence of a lifelong interest in and aptitude for science. This is clearly evidenced by his own writing in 1949 in an application for a national college scholarship program when he wrote: “Ever since I took my first science course in high school, I’ve been interested in the infinite possibilities of science.” When it came time to choose a college, George’s choice between Harvard and Brown University was based on the desire to attend one for college and the other for medical school. Choosing Brown University for undergraduate school was to have lifelong implications, as it was at …

BACKGROUND Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids. OBJECTIVES We examined the effects of weight-loss diets on long-term changes in plasma amino acids and the associations of these changes with weight loss and the improvement of insulin resistance. DESIGN We repeatedly measured plasma amino acid profiles over 2 y in overweight or obese participants from 2 randomized, dietary intervention, weight-loss trials [774 subjects from the POUNDS LOST (Preventing Overweight Using Novel Dietary Strategies Trial) and 318 subjects from the DIRECT (Dietary Intervention Randomized Controlled Trial)]. RESULTS Intervention diets consistently lowered most of the amino acid concentrations, including BCAAs and AAAs, in both trials. In the POUNDS LOST, average-protein diets (15% of daily energy) showed stronger effects than did high-protein diets (25% of daily energy) on reducing concentrations of the diabetes-associated BCAA valine at 6 mo independent of the weight change. In both trials, weight loss was directly related to the concurrent reduction of the BCAAs leucine and isoleucine, the AAAs tyrosine and phenylalanine, and 4 other amino acids. For example, per kilogram of weight loss, there was a 0.04-SD decrease in log tyrosine (∼0.6 μmol/L) in both trials. In addition, we showed that reductions in alanine and the AAA tyrosine were significantly related to improved insulin resistance (measured with the use of the homeostasis model assessment of insulin resistance), independent of weight loss, in both trials (both P < 0.05). For example, per 1-SD decrease in log tyrosine (∼17 μmol/L), there was a 0.04-SD (∼3%) improvement in insulin resistance in the POUNDS LOST and a 0.13-SD (∼8%) improvement in insulin resistance in the DIRECT. CONCLUSION Our findings underscore the potential importance of dietary interventions in improving amino acid profiles (i.e., reducing diabetes risk-enhancing amino acid concentrations) along with and beyond weight loss. The POUNDS LOST and the DIRECT were registered at clinicaltrials.gov as NCT00072995 and NCT00160108, respectively.

BACKGROUND: The effects of dietary composition on weight loss are incompletely understood. In addition to energy intake, fiber intake, energy density, macronutrient composition, and demographic characteristics have all been suggested to contribute to weight loss. OBJECTIVE: The primary aim of this analysis was to assess the role of dietary fiber as a predictor of weight loss in participants who consumed calorie-restricted diets (−750 kcal/d from estimated energy needs) for 6 mo, using data from the POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) Study—a randomized trial that examined the effects of calorie-restricted diets varying in macronutrient composition on weight loss in adults. METHODS: Data were randomly partitioned to a training data set (70%) in which the effects of fiber and other weight-loss predictors were identified using adjusted Least Absolute Shrinkage and Selection Operator and model averaging. The retained predictors were then fit on the testing data set to assess predictive performance. RESULTS: Three hundred and forty-five participants (53.9% female) provided dietary records at baseline and 6 mo. Mean ± SD age and BMI for the full sample was 52.5 ± 8.7 y and 32.6 ± 3.9 kg/m(2), respectively. Mean ± SD (99% CI) weight change at 6 mo for the full sample was −7.27 ± 5.6 kg (−8.05, −6.48 kg). The final, best fit model (R(2) = 0.41) included fiber, energy density, fat, age, adherence, baseline weight, race, and changes from baseline in carbohydrate, fiber, PUFA, and MUFA intake, but the most influential predictor was fiber intake ([Formula: see text] = −0.37; P

Efforts to identify a preferable diet for weight management based on macronutrient composition have largely failed, but recent evidence suggests that satiety effects of carbohydrates may depend on the individual&rsquo, s insulin-mediated cellular glucose uptake. Therefore, using data from the POUNDS LOST trial, pre-treatment fasting plasma glucose (FPG), fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as prognostic markers of long-term weight loss in four diets differing in carbohydrate, fat, and protein content, while assessing the role of dietary fiber intake. Subjects with FPG &lt, 100 mg/dL lost 2.6 (95% CI 0.9, 4.4, p = 0.003) kg more on the low-fat/high-protein (n = 132) compared to the low-fat/average-protein diet (n = 136). Subjects with HOMA-IR &ge, 4 lost 3.6 (95% CI 0.2, 7.1, p = 0.038) kg more body weight on the high-fat/high-protein (n = 35) compared to high-fat/average-protein diet (n = 33). Regardless of the randomized diet, subjects with prediabetes and FI below the median lost 5.6 kg (95% CI 0.6, 10.6, p = 0.030) more when consuming &ge, 35 g (n = 15) compared to &lt, 35 g dietary fiber/10 MJ (n = 16). Overall, subjects with normal glycemia lost most on the low-fat/high-protein diet, subjects with high HOMA-IR lost most on the high-fat/high protein diet, and subjects with prediabetes and low FI had particular benefit from dietary fiber in the diet.

As obesity rates increase, so too do the risks of type 2 diabetes, cardiovascular disease, and numerous other detrimental conditions. The prevalence of obesity in U.S. adults more than doubled between 1980 and 2010, from 15.0 to 36.1%. Although this trend may be leveling off, obesity and its individual, societal, and economic costs remain of grave concern. In June 2014, a Diabetes Care Editors’ Expert Forum convened to review the state of obesity research and discuss the latest prevention initiatives and behavioral, medical, and surgical therapies. This article, an outgrowth of the forum, offers an expansive view of the obesity epidemic, beginning with a discussion of its root causes. Recent insights into the genetic and physiological factors that influence body weight are reviewed, as are the pathophysiology of obesity-related metabolic dysfunction and the concept of metabolically healthy obesity. The authors address the crucial question of how much weight loss is necessary to yield meaningful benefits. They describe the challenges of behavioral modification and predictors of its success. The effects of diabetes pharmacotherapies on body weight are reviewed, including potential weight-neutral combination therapies. The authors also summarize the evidence for safety and efficacy of pharmacotherapeutic and surgical obesity treatments. The article concludes with an impassioned call for researchers, clinicians, governmental agencies, health policymakers, and health-related industries to collectively embrace the urgent mandate to improve prevention and treatment and for society at large to acknowledge and manage obesity as a serious disease.

Objective Adult obesity is recognized as a chronic disease. According to principles of chronic disease management, healthcare professionals should work collaboratively with patients to determine appropriate therapeutic strategies that address overweight and obesity, specifically considering a patient's disease status in addition to their individual needs, preferences, and attitudes regarding treatment. A central role and responsibility of healthcare professionals in this process is to inform and educate patients about their treatment options. Although current recommendations for the management of adult obesity provide general guidance regarding safe and proper implementation of lifestyle, pharmacological, and surgical interventions, healthcare professionals need awareness of specific evidence-based information that supports individualized clinical application of these therapies. More specifically, healthcare professionals should be up-to-date on approaches that promote successful lifestyle management and be knowledgeable about newer weight loss pharmacotherapies, so they can offer patients with obesity a wide range of options to personalize their treatment. Accordingly, this educational activity has been developed to provide participants with the latest information on treatment recommendations and therapeutic advances in lifestyle intervention and pharmacotherapy for adult obesity management. Design and Methods This supplement is based on the content presented at a live CME symposium held in conjunction with ObesityWeek 2014. Results This supplement provides an expert summary of current treatment recommendations and recent advances in nonsurgical therapies for the management of adult obesity. Patient and provider perspectives on obesity management are highlighted in embedded video clips available via QR codes, and new evidence will be applied using clinically relevant case studies. Conclusions This supplement provides a topical update of obesity management, including clinical practice examples, for healthcare professionals who treat or provide care for adults with obesity.

Background: Hepatic lipase (HL) plays a pivotal role in the metabolism of HDL and LDL. Recent genome-wide association studies have identified common variants in the HL gene (LIPC) associated with HDL cholesterol. Objective: We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial. Methods: We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30–70 y (61% women) who were assigned to high-fat (40% energy) or low-fat (20% energy) diets for 2 y. We measured serum concentrations of total cholesterol (TC), triglycerides, LDL cholesterol, and HDL cholesterol at baseline and 2 y of intervention. Results: At 2 y of intervention, dietary fat modified effects of the variant on changes in serum TC, LDL cholesterol, and HDL cholesterol (P-interaction: 0.0008, 0.004, and 0.03, respectively). In the low-fat group, as compared to the G allele, the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [TC (β ± SE): −5.5 ± 3.0, P = 0.07; LDL cholesterol: −4.8 ± 2.5, P = 0.06] and a lower increase in HDL cholesterol concentrations (β ± SE: −1.37 ± 0.69, P = 0.048), whereas an opposite effect in the high-fat diet group was evident [TC (β ± SE): 7.3 ± 2.7, P = 0.008; LDL cholesterol: 4.1 ± 2.3, P = 0.07], and there was no genetic effect on changes in HDL cholesterol concentrations (P = 0.54). Conclusion: Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00072995","term_id":"NCT00072995"}}NCT00072995.

Objective To determine whether there are differences in baseline psychological and behavioral characteristics between individuals with severe obesity who chose a surgical or nonsurgical intervention for weight loss. Methods The current study utilized data from a larger study funded by a state insurance company and is unique in that the insurance company funded the weight loss interventions. Participants indicated their preferred method of weight loss, and completed several self-report psychological questionnaires, as well as demographic information. Results Participants (N = 605) were 58.8% Caucasian and mostly (86%) female. Logistic regression results indicated that an increased number of weight loss attempts, and select other measures of eating behavior and quality of life may influence individuals’ selection for either surgical or nonsurgical treatments for weight loss. Conclusions Practitioners should pay particular attention to these baseline characteristics that influence choice to examine potential characteristics that may influence the success of these weight loss treatments.