Thomas A. Wadden

Lifestyle Modification and Incretin Therapy for Individuals With Obesity—Reply

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

This guideline provides evidence-based recommendations on lifestyle management, including dietary patterns and physical activity, to reduce cardiovascular risk.

NOV 2013EckelJournal of the American College of Cardiology

2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk

Brain activity associated with breakthrough food preoccupation in an individual on tirzepatide

Obesity and related conditions are associated with distressing food preoccupation that often culminates in dysregulated eating behaviors. Incretin-based therapies can reduce excessive weight in obesity, but their impact on dysregulated eating behaviors remains largely unexamined. Understanding how these pharmacologics engage the brain's mesolimbic circuitry may inform the expansion of their therapeutic potential. We report a rare, first-in-human exploration of the physiological action of these therapies by examining the electrophysiology directly within the human nucleus accumbens. After a short-term course of tirzepatide, the patient-participant exhibited increased severe food preoccupation episodes, which were preceded by an increased delta-theta frequency (≤7 Hz) power in the nucleus accumbens region. We propose that the effects of an incretin-based therapy (tirzepatide) on food preoccupation may be associated with modulation of aberrant activity within this key hub of human mesolimbic circuitry.

Internalized weight stigma, metabolic syndrome, and inflammation in postmenopausal women with obesity

Objective To determine the relationship of internalized weight stigma with metabolic syndrome (MetS) and markers of inflammation. Methods Postmenopausal women with obesity ( N =101) with high or low scores on the Weight Bias Internalization Scale completed a single assessment visit. MetS components (waist circumference, blood pressure, triglycerides, HDL cholesterol, and glucose) were measured, along with body mass index (BMI). Blood samples were drawn to analyze C-reactive protein, interleukin-6, and myeloperoxidase. Participants completed a second measure of internalized weight stigma (Weight Self-Stigma Questionnaire; WSSQ) and reported medications, demographics, depression symptoms, smoking status, and perceived stress (included as covariates). Results Logistic regression showed no significant relationship between either measure of internalized weight stigma and MetS when controlling for BMI, depression, and demographics. A small, significant, positive association emerged between WSSQ scores and MetS when adding the covariate of anti-depressant medication (OR=1.07, p =0.040). WSSQ scores were associated with significantly greater odds of having high blood pressure (OR=1.10, p =0.003) and low HDL cholesterol (OR=1.06, p =0.030). Both measures of internalized weight stigma were associated with greater continuous blood pressure values. Inflammatory markers were not associated with internalized weight stigma in most analyses. Conclusions Some significant associations were found between internalized weight stigma and MetS components, but more research is needed to clarify these relationships.

Feasibility and Acceptability of a Psychological Intervention for Internalized Health-Related Stigma Among Adults With Chronic Health Conditions: Preliminary Investigation

Preliminary investigation shows high acceptability of a group-based psychological intervention for internalized stigma in adults with chronic health conditions, suggesting broader applicability.

Association of the Early Response to an Oral Shape‐Shifting Superabsorbent Hydrogel Capsule With Weight Loss

Post hoc analysis reveals early response to Epitomee leads to improved weight loss outcomes compared to placebo.

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.).

Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial

Current guidelines recommend behavioral treatment (BT) as the first intervention for patients with obesity. However, a substantial minority (35–50%) do not achieve a clinically meaningful loss of ≥5%. Anti-obesity medications (AOMs) are recommended when target weight loss is not achieved; however, their efficacy among BT nonresponders has not been established. This double-blind, randomized controlled proof-of-principle study evaluated whether augmenting BT with AOM improved 24-week weight loss compared to BT with placebo in early nonresponders to BT. A total of 147 adults with a body mass index ≥31 kg m−2 (≥28 kg m−2 with obesity-related comorbidity) completed an initial 4-week BT run-in. The 76 early nonresponders who lost <2.0% of initial weight were then randomized to 24 weeks of either BT plus placebo (BT + P, n = 38) or BT plus AOM (phentermine = 15.0 mg d−1, n = 38). Early responders received ongoing BT and were not part of the randomized trial. The primary outcome was met; early nonresponders assigned to BT + AOM had a greater mean (±s.e.) reduction in weight of 5.9 ± 0.7% from randomization to week 24, as compared to 2.8 ± 0.7% for those assigned to BT + P (mean difference = 3.1 ± 1.0, 95% confidence interval = 1.1–5.1%, Cohen’s d = 0.73, P = 0.003). Stepping up early BT nonresponders to BT + AOM improves their 24-week weight loss. ClinicalTrials.gov registration: NCT03779048 . A randomized clinical trial showing the superiority of behavioral treatment plus phentermine to behavioral treatment plus placebo for weight loss in those that previously had not responded to behavioral treatment.

Characterising first, recent and worst experiences of weight stigma in a clinical sample of adults with high body weight and high internalised stigma

Summary This research aimed to systematically characterise experiences of weight stigma and their impacts among weight‐loss treatment‐seeking adults with high body weight and high levels of internalised weight stigma. Participants recruited for two clinical trials completed a semi‐structured interview about weight stigma (Study 1 n = 84, Mage = 47.8 ± 11.2 years, 83.3% women, 67.9% Black; Study 2 n = 129, Mage = 50.0 ± 12.2 years, 88.4% women, 65.1% White). Study 1 focused on first and most recent experiences of weight‐based teasing, bullying, discrimination and unfair treatment, and Study 2 focused on the worst examples of these experiences; participants in both studies also identified their overall worst experiences. Participants reported the age at which the experiences occurred and rated (1–5) how upsetting they were. Interview responses were coded for interpersonal sources of weight stigma and impacts of these experiences. Across studies, weight teasing was the most commonly reported experience of weight stigma and the most frequently identified worst experience. Family members were the most commonly identified interpersonal source of weight stigma. Weight stigma experiences were reported across the lifespan and were predominantly described as having negative emotional impacts. Findings provide insights into the types and characteristics of weight stigma experiences that may contribute to the internalisation of this stigma and other adverse consequences.

Efficacy and safety of a novel oral hydrogel capsule in adults with overweight or obesity: the pivotal randomized RESET study

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 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.

Weight and cardiometabolic effects of a novel oral shape-shifting superabsorbent hydrogel capsule: Prespecified and exploratory analysis of the Epitomee capsule RESET study

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].

Measuring internalized health-related stigma across health conditions: development and validation of the I-HEARTS Scale

The I-HEARTS Scale is a reliable and valid measure for the assessment of internalized health-related stigma among adults with varied stigmatized chronic health conditions. STUDY PRE-REGISTRATION: https://osf.io/84c5d/?view_only=87238512f6d6475c87f8f64280a8a15f .

Longitudinal associations of internalized weight stigma with physical activity and weight loss

Objective Cross‐sectional research has demonstrated that internalized weight stigma (IWS) is associated with less engagement in weight management behaviors, including physical activity. However, limited research has explored longitudinal relationships among IWS, physical activity, and weight loss. This study examined longitudinal associations of changes in IWS, physical activity, and weight and tested whether physical activity mediated the relationship between IWS and weight change. Methods Individuals with obesity and high IWS ( N = 105) participated in a 72‐week behavioral weight loss intervention, with or without a weight stigma intervention. Measures of IWS (Weight Self‐Stigma Questionnaire), physical activity (accelerometry and self‐report), and weight were collected at baseline and weeks 20, 46 and 72. Correlations examined relationships among changes in variables from baseline to all timepoints, controlling for treatment condition. Mediation, controlling for treatment condition, tested whether IWS reductions during the first 20 weeks predicted greater weight loss at weeks 46 and 72 via increased physical activity between weeks 20 and 46 or 72. Results Decreases in IWS at week 20 were associated with greater week‐20 weight loss ( r = 0.265, p = 0.012). Physical activity was not a significant mediator, but greater reductions in IWS at week 20 predicted greater week‐46 weight loss with or without controlling for physical activity (WSSQ: b = 0.30, confidence interval: 0.12, 0.54). Significant associations were not found at week 72. Conclusion Initial reductions in IWS were associated with greater week‐46 weight loss. Further research should investigate whether reducing IWS early in obesity treatment enhances long‐term outcomes. Clinical trial registration ClinicalTrials.gov (NCT03704064).

Neural Responses to Auditory Food Stimuli Following Cognitive Behavioral Therapy for Binge‐Eating Disorder

Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC).

Nutritional considerations with antiobesity medications

The improved efficacy and generally favorable safety profile of recently approved and emerging antiobesity medications (AOMs), which result in an average weight reduction of ≥15%, represent significant advancement in the treatment of obesity. This narrative review aims to provide practical evidence-based recommendations for nutritional assessment, management, and monitoring of patients treated with AOMs. Prior to treatment, clinicians can identify preexisting nutritional risk factors and counsel their patients on recommended intakes of protein, dietary fiber, micronutrients, and fluids. During treatment with AOMs, ongoing monitoring can facilitate early recognition and management of gastrointestinal symptoms or inadequate nutrient or fluid intake. Attention should also be paid to other factors that can impact response to treatment and quality of life, such as physical activity and social and emotional health. In the context of treatment with AOMs, clinicians can play an active role in supporting their patients with obesity to improve their health and well-being and promote optimal nutritional and medical outcomes.

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

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.

Effect of semaglutide 2.4 mg on physical functioning and weight‐ and health‐related quality of life in adults with overweight or obesity: Patient‐reported outcomes from the STEP 1–4 trials

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.