Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes.

OBJECTIVE: The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization. METHODS: Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.4) years and BMI 34.9 (5.1) kg/m2 at randomization. Dual-energy x-ray absorptiometry measured total and regional fat and lean masses at randomization, at Years 1, 4, and 8, and at the final visit. Linear mixed-effects regressions were applied with adjustment for group, clinic, sex, age, race/ethnicity, and baseline body composition. RESULTS: Weight and most body compartments were reduced by 2% to 8% (and BMI 4%) in ILI versus DSE in men but not women. ILI-induced loss of lean tissue did not show a lower percent lean mass versus DSE at 16 years after randomization. CONCLUSION: ILI-related changes in weight, fat, and lean mass were detectable 12 to 16 years after randomization in men but, for unknown reasons, not in women. There was no evidence that the intervention led to a disproportionate loss of lean mass by the end of the study.

The past, present, and future of behavioral obesity treatment.

Over the last century, hundreds of evaluations have been conducted to examine weight-management interventions related to diet, physical activity, and behavior therapy. These investigations have contributed to a growing body of knowledge that has consistently advanced the field of obesity treatment, while also revealing some persistent challenges. This narrative review summarizes key findings from randomized controlled trials conducted in adults that have combined diet, physical activity, and behavior therapy, an approach variously referred to as behavioral treatment, comprehensive lifestyle modification, or intensive lifestyle intervention. The review shows that current behavioral approaches induce average reductions in baseline body weight of 5 to 10% at 6 to 12 months. Such losses have proven effective in reducing the risk of type 2 diabetes in persons with impaired glucose tolerance and in improving other obesity-related complications. These benefits have also been associated with reductions in healthcare costs. Despite these advances, behavioral treatment is challenged by the need for larger losses to achieve optimal improvements in health, by difficulties associated with maintaining weight loss, and by barriers limiting access to treatment. New anti-obesity medications, when combined with behavioral obesity treatment, hold promise of addressing the first two issues.

Psychopathology, disordered eating, and impulsivity as predictors of weight loss 24 months after metabolic and bariatric surgery.

BACKGROUND: The relationship between theoretically relevant psychosocial and behavioral variables and outcomes of metabolic and bariatric surgery remains unclear. Some studies have found that the presence of psychopathology, disordered eating, and impulsivity, either before surgery or during the early postoperative period, is associated with suboptimal postoperative weight loss. Other studies have not found these relationships. OBJECTIVE: Examine the relationship between psychopathology, disordered eating, impulsivity, and weight loss 24 months postoperatively. SETTING: Two large, urban university health systems. METHODS: Participant characteristics were collected using validated interviews, patient-reported outcome measures, and computerized assessment methods. Linear mixed effect models were used to test the association of the variables of interest on percent weight loss (%WL). RESULTS: Three hundred participants were enrolled at baseline; weight data at 24 months were available for 227 participants; between 181 and 53 individuals completed other outcome measures. The mean %WL was 23.3 ± 9.9% at 24 months. Patients who underwent Roux-en-Y gastric bypass lost more weight than those who underwent sleeve gastrectomy. The presence of subjective binge episodes at baseline was related to a greater %WL at 24 months; there were no other baseline predictors. The presence of eating disorder diagnoses and disordered eating symptoms after surgery were associated with smaller weight losses over 24 months. Current and lifetime psychopathology and impulsivity were unrelated to %WL at 24 months. CONCLUSION: Disordered eating after bariatric surgery was associated with a smaller %WL at postoperative year 2. Additional monitoring of these symptoms in the early postoperative period is recommended. Psychotherapeutic and/or dietary interventions may promote more optimal weight loss outcomes.

Randomized Controlled Trial of Effects of Behavioral Weight Loss Treatment on Food Cue Reactivity.

BACKGROUND: It is not known whether behavioral weight loss can attenuate blood oxygen level-dependent responses to food stimuli. OBJECTIVES: This randomized controlled trial assessed the effects of a commercially available behavioral weight loss program (WW, WeightWatchers) compared to a wait-list control on blood oxygen level-dependent response to food cues. METHODS: Females with obesity ( N = 61) were randomized to behavioral weight loss or wait-list control. At baseline and follow-up, participants completed assessments that included functional magnetic resonance imaging scans to assess response to images of high-calorie foods (HCF) or low-calorie foods (LCF), and neutral objects. RESULTS: There were no significant between-group differences in change from baseline to follow-up in any regions of the brain in response to viewing HCF or LCF. From baseline to follow-up, participants in behavioral weight loss, compared with wait-list control, reported significantly greater increases in desire for LCF. Changes in liking and palatability of LCF and liking, palatability, and desire for HCF did not differ between groups. DISCUSSION: Behavioral weight loss was associated with increased desire for LCF without changes in neural reactivity to food cues. These results suggest that alteration of neurological processes underlying responsiveness to food is difficult to achieve through behavioral weight management alone.

Prevalence of diagnosed psychiatric disorders among adults who have experienced and internalized weight stigma.

Objective: Experiences and internalization of weight stigma are associated with greater self-reported psychological distress and symptoms of psychiatric disorders such as depression and anxiety. However, little is known about the extent to which individuals who have experienced and internalized weight stigma are diagnosed with or provided treatment for psychiatric conditions. The current study aimed to characterize the prevalence of diagnosed psychiatric disorders among adults with obesity who had experienced and internalized weight stigma. Methods: Weight-loss treatment-seeking adults with a history of experiencing weight stigma and high levels of internalized weight stigma were recruited for two clinical trials. Results: In Study 1 (n = 84, 83.3% women, 67.9% Black), 25% of participants reported a lifetime history of a mood disorder. Few participants (<10%) reported current psychiatric diagnoses or use of psychiatric medications. In Study 2 (n = 129, 88.4% women, 65.1% white), one-third of participants reported a mood disorder history, and 21.7% reported an anxiety disorder history, with approximately 16%-18% reporting current diagnoses. In both studies, few participants reported a history of a diagnosed eating disorder despite high rates of current full- or subthreshold symptoms. Based on Beck Depression Inventory-II scores, approximately 54%-64% of participants reported mild or greater symptoms of depression. Conclusions: Overall, lifetime history of diagnosed psychiatric disorders and current symptoms of depression and eating disorders were relatively high across two samples. More research is needed to determine the impact of weight stigma on the diagnosis and treatment of eating disorders and other psychiatric concerns.

The Role of Lifestyle Modification with Second-Generation Anti-obesity Medications: Comparisons, Questions, and Clinical Opportunities.

PURPOSE OF REVIEW: This review examines lifestyle modification for obesity management with the goal of identifying treatment components that could support the use of a new generation of anti-obesity medications (AOMs). RECENT FINDINGS: Semaglutide reliably reduces baseline body weight by approximately 15% at 68 weeks, in contrast to 5-10% for lifestyle modification. Tirzepatide induces mean losses as great as 20.9%. Both medications reduce energy intake by markedly enhancing satiation and decreasing hunger, and they appear to lessen the need for traditional cognitive and behavioral strategies (e.g., monitoring food intake) to achieve calorie restriction. Little, however, is known about whether patients who lose weight with these AOMs adopt healthy diet and activity patterns needed to optimize body composition, cardiometabolic health, and quality of life. When used with the new AOMs, the focus of lifestyle modification is likely to change from inducing weight loss (through calorie restriction) to facilitating patients' adoption of dietary and activity patterns that will promote optimal changes in body composition and overall health.

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial.

The effects of tirzepatide, a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, on weight reduction after successful intensive lifestyle intervention are unknown. This double-blind, placebo-controlled trial randomized (1:1) adults with body mass index ≥30 or ≥27 kg/m2 and at least one obesity-related complication (excluding diabetes), who achieved ≥5.0% weight reduction after a 12-week intensive lifestyle intervention, to tirzepatide maximum tolerated dose (10 or 15 mg) or placebo once weekly for 72 weeks (n = 579). The treatment regimen estimand assessed effects regardless of treatment adherence in the intention-to-treat population. The coprimary endpoint of additional mean per cent weight change from randomization to week 72 was met with changes of -18.4% (standard error (s.e.) 0.7) with tirzepatide and 2.5% (s.e. 1.0) with placebo (estimated treatment difference -20.8 percentage points (95% confidence interval (CI) -23.2%, -18.5%; P < 0.001). The coprimary endpoint of the percentage of participants achieving additional weight reduction ≥5% was met with 87.5% (s.e. 2.2) with tirzepatide and 16.5% (s.e. 3.0) with placebo achieving this threshold (odds ratio 34.6%; 95% CI 19.2%, 62.6%; P < 0.001). The most common adverse events with tirzepatide were gastrointestinal, with most being mild to moderate in severity. Tirzepatide provided substantial additional reduction in body weight in participants who had achieved ≥5.0% weight reduction with intensive lifestyle intervention. ClinicalTrials.gov registration: NCT04657016 .

Giving weight to incretin-based pharmacotherapy for obesity-related sleep apnea: a revolution or a pipe dream?

Obesity is a chronic disease affecting over 670 million adults globally, with multiple complications including obstructive sleep apnea (OSA). Substantial weight loss in patients with obesity-related OSA can reduce or even eliminate OSA as well as reduce sleepiness and improve cardio-metabolic health. Evidence suggests that these improvements exceed those that occur with device-based OSA therapies like continuous positive airway pressure which continue to be the first-line of therapy. Resistance to weight management as a first-line strategy to combat OSA could arise from the complexities in delivering and maintaining adequate weight management, particularly in sleep clinic settings. Recently, incretin-based pharmacotherapies including glucagon-like peptide 1 (GLP-1) receptor agonists alone or combined with glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been developed to target glycemic control in type 2 diabetes. These medications also slow gastric emptying and reduce energy intake. In randomized, placebo-controlled trials of these medications in diabetic and non-diabetic populations with obesity, participants on active medication lost up to 20% of their body weight, with corresponding improvements in blood pressure, lipid levels, physical functioning, and fat mass loss. Their adverse effects are predominantly gastrointestinal-related, mild, and transient. There are trials currently underway within individuals with obesity-related OSA, with a focus on reduction in weight, OSA severity, and cardio-metabolic outcomes. These medications have the potential to substantially disrupt the management of OSA. Pending coming data, we will need to consider pharmacological weight loss as a first-line therapy and how that influences training and management guidelines.

Development of a cognitive-behavioral intervention for internalized weight stigma.

Individuals with a higher body weight are the targets of pervasive social stigma. This stigma can become self-directed or internalized, leading to self-devaluation due to weight. Internalized weight stigma is associated with adverse outcomes for mental and physical health, yet little is known about how to prevent or diminish this internalization. This article introduces a novel, group-based, psychological intervention designed to reduce internalized weight stigma and its ill effects on health. Rationale is provided for the therapeutic approach and for the intervention's proposed utility in behavioral weight management settings. Intervention content is described in detail, along with preliminary evidence of its potential effects on psychological and behavioral outcomes.

Long-term effects of an internalized weight stigma intervention: A randomized controlled trial.

OBJECTIVE: To test the long-term effects of a group-based, psychological intervention designed to reduce internalized weight stigma (IWS, i.e., self-stigma), delivered in combination with behavioral weight loss (BWL) treatment, compared to BWL alone. METHOD: Adults with obesity who had experienced and IWS (N = 105, Mage = 49 years, 90.5% women, 70.5% White, 24.8% Black, MBMI = 38 kg/m²) were randomized to receive BWL with the Weight Bias Internalization and Stigma (BIAS) Program or BWL alone. Participants received weekly group treatment for 20 weeks, followed by 52 weeks of monthly and every-other-month sessions. Percent weight change at Week 72 was the primary outcome, with secondary outcomes of weight change at other time points; physical activity (measured by accelerometry, interview, and self-report); cardiometabolic risk factors; and psychological and behavioral outcomes. Intention-to-treat analyses used linear mixed models to test for between-group differences. Treatment acceptability was assessed. RESULTS: Participants in the BWL + BIAS versus BWL group lost 2 percentage points more of baseline weight at Week 72, which was not a significant difference (mean weight change = -7.2% vs. -5.2%, 95% CI [-4.6 to 0.6], p = 0.14, d = 0.18). The BWL + BIAS (vs. BWL) group produced significantly greater improvements in weight self-stigma, eating self-efficacy, and some aspects of quality of life at specific time points. Most outcomes improved significantly over time but did not differ between groups. The trial had high retention and treatment acceptability, with higher ratings in the BWL + BIAS versus BWL group. CONCLUSIONS: No significant differences in weight loss were observed between the BWL + BIAS versus BWL group. Possible benefits of addressing weight stigma in weight management warrant further investigation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A randomized controlled trial examining the effects of behavioral weight loss treatment on hippocampal volume and neurocognition.

BACKGROUND/PURPOSE: Obesity in midlife is an established risk factor for dementia. In middle-aged adults, elevated body mass index (BMI) is associated with lower neurocognition and smaller hippocampal volumes. It is unclear whether behavioral weight loss (BWL) can improve neurocognition. The purpose of this study was to evaluate whether BWL, compared to wait list control (WLC), improved hippocampal volume and neurocognition. We also examined if baseline hippocampal volume and neurocognition were associated with weight loss. METHODS: We randomly assigned women with obesity (N = 61; mean±SD age=41.1 ± 9.9 years; BMI=38.6 ± 6.2 kg/m2; and 50.8% Black) to BWL or WLC. Participants completed assessments at baseline and follow-up including T1-weighted structural magnetic resonance imaging scans and the National Institutes of Health (NIH) Toolbox Cognition Battery. RESULTS: The BWL group lost 4.7 ± 4.9% of initial body weight at 16-25 weeks, which was significantly more than the WLC group which gained 0.2 ± 3.5% (p < 0.001). The BWL and WLC groups did not differ significantly in changes in hippocampal volume or neurocognition (ps>0.05). Baseline hippocampal volume and neurocognition scores were not significantly associated with weight loss (ps>0.05). CONCLUSIONS AND IMPLICATIONS: Contrary to our hypothesis, we found no overall benefit of BWL relative to WLC on hippocampal volumes or cognition in young- and middle-aged women. Baseline hippocampal volume and neurocognition were not associated with weight loss.

A pilot randomized controlled trial of liraglutide 3.0 mg for binge eating disorder.

Objective: To assess the efficacy of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, for binge eating disorder (BED). Methods: Adults with a body mass index (BMI) ≥ 27 kg/m2 enrolled in a pilot, 17-week double-blind, randomized controlled trial of liraglutide 3.0 mg/day for BED. The primary outcome was number of objective binge episodes (OBEs)/week. Binge remission, weight change, and psychosocial variables were secondary outcomes. Mixed effect models were used for continuous variables, and generalized estimating equations were used for remission rates. Results: Participants (n = 27) were 44.2 ± 10.6 years; BMI = 37.9 ± 11.8 kg/m2; 63% women; and 59% White and 41% Black. At baseline, the liraglutide group (n = 13) reported 4.7 ± 0.7 OBEs/week, compared with 3.0 ± 0.7 OBEs/week for the placebo group, p = 0.07. At week 17, OBEs/week decreased by 4.0 ± 0.6 in liraglutide participants and by 2.5 ± 0.5 in placebo participants (p = 0.37, mean difference = 1.2, 95% confidence interval 1.3, 2.0). BED remission rates of 44% and 36%, respectively, did not differ. Percent weight loss was significantly greater in the liraglutide versus the placebo group (5.2 ± 1.0% vs. 0.9 ± 0.7%, p = 0.005). Conclusion: Participants in both groups reported reductions in OBEs, with the liraglutide group showing clinically meaningful weight loss. A pharmacy medication dispensing error was a significant limitation of this study. Further research on liraglutide and other GLP-1 agonists for BED is warranted.

Two-year effect of semaglutide 2.4 mg on control of eating in adults with overweight/obesity: STEP 5.

OBJECTIVE: This study evaluated the effect of once-weekly semaglutide 2.4 mg on 2-year control of eating. METHODS: In STEP 5, adults with overweight/obesity were randomized 1:1 to semaglutide 2.4 mg or placebo, plus lifestyle modification, for 104 weeks. A 19-item Control of Eating Questionnaire was administered at weeks 0, 20, 52, and 104 in a subgroup of participants. P values were not controlled for multiplicity. RESULTS: In participants completing the Control of Eating Questionnaire (semaglutide, n = 88; placebo, n = 86), mean body weight changes were -14.8% (semaglutide) and -2.4% (placebo). Scores significantly improved with semaglutide versus placebo for Craving Control and Craving for Savory domains at weeks 20, 52, and 104 (p < 0.01); for Positive Mood and Craving for Sweet domains at weeks 20 and 52 (p < 0.05); and for hunger and fullness at week 20 (p < 0.001). Improvements in craving domain scores were positively correlated with reductions in body weight from baseline to week 104 with semaglutide. At 104 weeks, scores for desire to eat salty and spicy food, cravings for dairy and starchy foods, difficulty in resisting cravings, and control of eating were significantly reduced with semaglutide versus placebo (all p < 0.05). CONCLUSIONS: In adults with overweight/obesity, semaglutide 2.4 mg improved short- and longer-term control of eating associated with substantial weight loss.

Changes in Eating Behaviors and Their Relation to Weight Change 6 and 12 Months After Bariatric Surgery.

INTRODUCTION: Identifying eating behaviors associated with suboptimal weight loss following bariatric surgery remains important. This study assessed the relationship between eating behaviors and weight loss following bariatric surgery in a racially diverse sample. METHODS: Participants were assessed before surgery and 6 and 12 months postoperatively, with the Structured Clinical Interview for DSM-5, the Eating Disorder Examination-Bariatric Surgery Version, and validated measures assessing a range of eating behaviors. Linear mixed effect models were used to test the impact of eating behaviors on percent weight loss (%WL) at 6 and 12 months. RESULTS: We enrolled 300 participants (mean age 40.1 years; BMI 45.9 kg/m2; 87% women; 62% Black and 30% White). The majority (82%) underwent sleeve gastrectomy (SG). Mean %WL was 23.0 ± 5.1% at 6 months and 26.2 ± 7.6% at 12 months. Subjective binge episodes prior to surgery predicted greater %WL over the first 12 postoperative months (p = 0.028). Postoperative disinhibition, hunger, night eating symptoms, objective binge episodes, global disordered eating attitudes and behaviors, and snacks per day were associated with smaller %WL over 12 months (all p's < 0.01). The presence of picking/nibbling and addictive-like eating behaviors was not associated with %WL at the end of the first postoperative year. CONCLUSION: Among a diverse participant sample, problematic eating behaviors following surgery were associated with smaller %WL over 12 months. Postoperative assessment and treatment of eating behaviors are needed to address these issues as they arise and to prevent attenuation of early weight loss in some patients.

Refining the conceptualization and assessment of internalized weight stigma: A mixed methods approach.

Internalized weight stigma has gained increasing attention in empirical studies, though questions remain about the adequacy of existing measures. The current study utilized a mixed methods approach, including a novel semi-structured interview, to revisit the conceptualization of internalized weight stigma and explore in more depth the stereotypes and impacts of weight reported by individuals with high scores on the widely-used Weight Bias Internalization Scale. All participants were interviewed as part of the screening procedures for two clinical trials (Study 1 n = 84, mean age=47.8 years, 83.3% women, 67.9% Black, mean BMI=39.2 kg/m2; Study 2 n = 129, mean age=50.0 years, 88.4% women, 65.1% white, mean BMI=37.8 kg/m2). The most common weight stereotypes identified were being lazy, lacking willpower or self-control, and having poor eating habits. Up to 66% of participants reported that they did not endorse negative weight stereotypes or apply them to themselves. The most highly identified impacts of weight were on self-image (>70%) and emotions (68-83%), followed by social (37-62%) and health concerns (20-25%). Approximately 60% of participants indicated that weight affected their self-directed thoughts and feelings "very much" to "extremely." Findings have implications for understanding and assessing internalized weight stigma in research and in clinical settings where interventions are needed.

Weight changes during the COVID-19 shutdown in older individuals with type 2 diabetes: the Look AHEAD Study.

OBJECTIVE: The aims of this study were as follows: 1) examine weight changes in older adults (mean age = 76 years) with type 2 diabetes and overweight or obesity during the COVID-19 shutdown; and 2) compare the behavioral and psychosocial effects of the shutdown in those who had large weight losses (>5%), those who had small weight losses (2%-5%), those who remained weight stable (±2%), or those who gained weight (>2%). METHODS: Look AHEAD (Action for Health in Diabetes) participants (N = 2544) were surveyed during the COVID-19 shutdown (2020), and they self-reported their current weight, reasons for weight change, weight-related behaviors, psychosocial measures, and negative and positive effects of the pandemic on their lives. RESULTS: Comparing self-reported weight during the COVID-19 shutdown with earlier measured weight, Look AHEAD participants lost, on average, 2.2 kg during the COVID-19 shutdown: 47% lost >2%, and only 18% gained >2% (p < 0.0001). Decreases in physical activity and increases in screen time were reported frequently in all weight-change categories. Similarly, there were few differences among the categories on standardized psychosocial measures or self-reported effects of the shutdown on participants' lives. However, when differences were seen, the most negative impact was in those who gained weight. CONCLUSIONS: Although weight loss appeared more common than weight gain during the shutdown, the weight-change groups did not differ on most psychosocial and behavioral variables.

Semaglutide for the treatment of obesity.

Semaglutide is a glucagon-like peptide-1 receptor agonist that was recently approved by the US Food and Drug Administration for chronic weight management. This paper reviews data on the mechanism of action, weight-loss and cardiometabolic efficacy, and safety of semaglutide 2.4 mg/week for obesity. Semaglutide has demonstrated the largest weight loss of any obesity medication to date with reductions of approximately 15% of initial weight at 68 weeks, accompanied by improvements in cardiovascular risks factors and physical functioning. The approval of this medication provides patients with greater options for weight management.

Psychological resilience in older adults with type 2 diabetes from the Look AHEAD Trial.

BACKGROUND: There is growing interest in identifying factors associated with healthy aging. This cross-sectional study evaluated associations of psychological resilience with factors associated with aging in older adults with type 2 diabetes mellitus (T2DM). METHODS: Participants were 3199 adults (72.2 ± 6.2 years of age, 61% female, 61% White, body mass index [BMI] = 34.2 ± 8.2 kg/m2 ) with T2DM enrolled in Look AHEAD (a multi-site randomized clinical trial comparing an intensive lifestyle intervention for weight loss to diabetes education and support). Participants were followed observationally after the 10-year intervention was discontinued. The following items were assessed approximately 14.4 years post-randomization in a cross-sectional analysis: Brief Resilience Scale; overnight hospitalizations in past year; physical functioning measured objectively (gait speed, grip strength) and via self-report (Pepper Assessment Tool for Disability; physical quality of life [QOL; SF-36]); a measure of phenotypic frailty based on having ≥3 of unintentional weight loss, low energy, slow gait, reduced grip strength, and physical inactivity. Depressive symptoms (PHQ-9) and mental QOL (SF-36) were also measured. Logistic/linear/multinomial regression was used to evaluate the association of variables with resilience adjusted for age, race/ethnicity, and gender. RESULTS: Greater psychological resilience was associated with lower BMI, fewer hospitalizations, better physical functioning (i.e., lower self-reported disability, better physical QOL, faster gait speed, greater grip strength, lower likelihood of frailty), fewer depressive symptoms, and greater mental QOL (all p < 0.05). Psychological resilience moderated the relationship of number of hospitalizations in the past year with self-reported disability and grip strength. CONCLUSIONS: Psychological resilience is associated with better physical function and QOL among older adults. Results should be interpreted cautiously given cross-sectional nature of analyses. Exploring the clinical benefits of resilience is consistent with efforts to shift the narrative on aging beyond "loss and decline" to highlight opportunities to facilitate healthy aging.