Across species, stress drives alterations in feeding behaviour, including heightened food-seeking and the overconsumption of palatable foods. The bed nucleus of the stria terminalis (BNST) acts as a neural hub linking stress and reward circuits. However, its role in human food cue and taste processing under stress remains unclear. Here, using 7-Tesla fMRI, dynamic causal modelling and in-scanner taste delivery, we demonstrate that beverage cues and taste receipt under stress modulate BNST effective connectivity. Forty-eight participants were presented a palatable and neutral beverage cue before receiving the corresponding beverages under low- and high-stress conditions. Beverage cues under stress downregulated BNST effective connectivity to the nucleus accumbens, orbitofrontal cortex, and dorsal mid-insula (dmINS), with the strength of cue-related downregulation of BNST-to-orbitofrontal effective connectivity related to changes in participants' subjective stress. In addition, taste receipt under stress downregulated effective connectivity from the dmINS to BNST. These findings provide evidence that stress-related food cue and taste processing modulates BNST reward circuitry, offering a mechanistic perspective on how stress alters responsivity to food cues.

OBJECTIVE:To estimate population-level eligibility for glucagon-like peptide-1 receptor agonist (GLP-1RA) medications among adults in Australia, according to Therapeutic Goods Administration-approved indications for chronic weight management and secondary prevention of cardiovascular disease in individuals with overweight or obesity. STUDY TYPE:Cross-sectional analysis of data from the Australian Bureau of Statistics 2022 National Health Survey. SETTING, PARTICIPANTS:Non-pregnant adults aged ≥ 18 years who were residents of Australia living in a private dwelling. MAIN OUTCOME MEASURES:Total number of adults eligible for GLP-1RA medications according to approved indications for chronic weight management and secondary prevention of cardiovascular disease in individuals with overweight or obesity, across subgroups defined by body mass index, weight-related comorbidities and/or sociodemographic factors. RESULTS:Overall, 39.7% (95% confidence interval [CI], 38.4%-41.0%) of adults were eligible for GLP-1RA use for chronic weight management, accounting for 7.8 million (95% CI, 7.6-8.1 million) individuals. Among those eligible, 2.9 million (95% CI, 2.7-3.1 million) adults had no weight-related comorbidities, 3.3 million (95% CI, 3.1-3.4 million) adults had one weight-related comorbidity and 1.7 million (95% CI, 1.6-1.8 million) adults had at least two weight-related comorbidities. The proportion of adults eligible under this indication varied across clinical and sociodemographic factors. Among those eligible under the chronic weight management indication, up to 338.9 thousand (95% CI, 271.3-406.5 thousand) adults also met the indication criteria for secondary prevention of cardiovascular disease. CONCLUSION:About 7.8 million Australian adults are eligible to access GLP-1RAs for chronic weight management, with up to 338.9 thousand adults also qualifying according to the indication for established cardiovascular disease. This study provides a valuable reference for policymakers to understand the number of adults in Australia who may access GLP-1RA medications based on approved indication criteria and under various coverage scenarios.

This narrative review provides an overview of progress in the development of obesity medications, including a synthesis of data describing the efficacy and safety of currently available agents and emerging therapeutic options. Historically, many obesity medications have been withdrawn from the market due to safety concerns. However, expansion in scientific knowledge of the mechanisms regulating appetite and energy balance has led to the development of medications with greater safety and efficacy. The current generation of injectable incretin analogs, semaglutide and tirzepatide, is associated with mean weight loss in the range of 15%-20% over approximately 12-18 months. These agents confer additional substantial cardiometabolic benefits, including reductions in adverse cardiovascular and kidney outcomes, and improvements in glycaemia, blood pressure, lipid profile and steatohepatitis. As therapeutic options continue to expand, obesity medications are poised to play a critical role in the management of cardiometabolic disease.

ABSTRACT Objective In July 2023 a diverse group of international experts from academia, healthcare and medical technology/pharmacological companies gathered to discuss the current global landscape in the management of obesity, identify the clinical challenges healthcare systems are facing, and the gaps in scientific knowledge. Approach We proposed ways that the academia‐industry‐healthcare‐interface can be strengthened to offer solutions to these challenges and fill the gaps in knowledge. Conclusion We identified these five priorities for action: (1) Enhancing the academia‐healthcare‐industry collaboration in a way that prioritizes the patient with obesity and healthcare economic value. (2) Identifying reliable biomarkers and predictors of obesity treatment response to determine as early as possible whether a specific therapy is likely to work. (3) Defining specific and individualized treatment targets that take account of heterogeneity of obesity‐related complications risk, the presence of multimorbidity, and patient preference. (4) Addressing bias and discrimination against people with obesity amongst clinicians, health policy makers and the wider public. (5) Combining randomized controlled trial and cohort study data to apply next generation “machine learning” and “artificial intelligence” methods to large datasets that accelerates identification of factors associated with response heterogeneity and successful treatment response prediction.

With the advent of new effective treatments for obesity, the field is rapidly changing creating an urgent need for evidence to guide best patient management. To help prioritise and plan for future trials, a meeting of experts was convened with the aim of reviewing the current literature to identify and prioritise current knowledge gaps; identify relevant research questions, and discuss appropriate trial methodologies that could be utilised to address the identified gaps in a timely and pragmatic manner. Participants included research-active academic surgeons and physicians, and industry representatives from various pharmaceutical and device companies. This report summarizes the key outcomes from this meeting. Treatment options for obesity are rapidly evolving. To provide best personalised care for patients, more evidence is required to understand how to best utilise currently available treatments as well as combine treatments. Trials focused on improving the treatment of obesity may need to be pragmatic and more agile than the traditional RCT to enable real time impact on patient care.

Adiposity magnitude and distribution strongly influence the risk of prediabetes and type 2 diabetes (T2D). While metabolic bariatric surgery provides durable weight loss and metabolic improvement, optimal anthropometric and body composition targets for hyperglycemia remission remain undefined. We conducted a prospective cohort study of women undergoing sleeve gastrectomy (SG) in Melbourne, Australia (2019–2022). Anthropometric, biochemical, and dual-energy X-ray absorptiometry (DXA) derived body composition data were collected at baseline and 12 months post-surgery. The primary outcome was change in body composition. Secondary outcomes included percentage total body weight loss (

Abstract Background A sense of loss of control over eating, such that eating occurs despite the intent not to, is common in people with obesity and eating disorders such as binge eating disorder and bulimia nervosa. Currently, options for management of loss of control eating are limited. We recently determined that the pro-drug N-acetylcysteine (NAC) reduces compulsive-like eating in a rat model of diet-induced obesity. We will now conduct a single site, open-label pilot study to examine the feasibility of a randomized controlled trial (RCT) of NAC for loss of control eating in humans. Methods Thirty-six adult volunteers with loss of control eating will be enrolled. All participants will receive NAC at a dose of 1200 mg orally twice daily for 12 weeks. Eating behaviors and triggers will be assessed before and after the NAC treatment period using questionnaires (Eating Loss of Control Scale, Palatable Eating Motives Scale: Coping Subscale, Food Craving Inventory, Reward-Based Eating Scale, Perceived Stress Scale, and Emotional Eating Scale) and ecological momentary assessment (EMA). The primary outcomes of this feasibility study are recruitment rate, participant retention rate at week 12, and medication adherence. The secondary outcome is change in Eating Loss of Control Scale score from baseline to week 12. Exploratory data will be collected on the change in eating behaviors from baseline to week 12. Although EMA can provide real-time data on eating behaviors compared with retrospective questionnaires, it relies on repeated daily measurement for long periods which can affect participant’s adherence to study protocol. Therefore, this feasibility study will assess the performance of EMA versus retrospective questionnaires and will determine which approach suits the purposes of the research. Discussion The results of this study will inform the feasibility of a RCT of NAC for loss of control eating using EMA. Trial registration This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry in June 2022 (ACTRN12622000902796).

BACKGROUND:Exercise is recommended to manage hip osteoarthritis, but weight loss recommendations are conflicting. OBJECTIVE:To evaluate the efficacy of a weight loss diet added to exercise on change in hip pain. DESIGN:2-group superiority randomized trial. (ClinicalTrials.gov: NCT04825483). SETTING:Community. PARTICIPANTS:101 adults with hip osteoarthritis and overweight or obesity. INTERVENTION:Both the exercise only group and very-low-calorie diet (VLCD) plus exercise group were provided with a 6-month home exercise program via 5 telehealth consultations. The VLCD plus exercise group also received a VLCD via 6 telehealth consultations. MEASUREMENTS:The primary outcome was 6-month change in hip pain severity (11-point scale; range 0 to 10, with higher scores indicating worse pain; minimum clinically important difference of 1.8). Secondary end points included other measures of hip pain, physical function, quality of life, body weight, body composition, and adverse events. RESULTS:99 (98%) and 95 (94%) participants provided 6- and 12-month primary outcomes, respectively. Although VLCD plus exercise lost 8.5% more weight than exercise only, VLCD plus exercise was not more effective for change in hip pain severity (mean difference, -0.6 units [95% CI, -1.5 to 0.3]) at 6 months. Between-group differences for other secondary outcomes at 6 months favored VLCD plus exercise except Hip Disability and Osteoarthritis Outcome Score (HOOS) pain and function. At 12 months, weight, body mass index, HOOS pain and function, and overall hip improvement, but not quality of life and physical activity, favored VLCD plus exercise. There were no serious related adverse events. LIMITATION:Participants were unblinded. CONCLUSION:Adding a weight loss diet to exercise did not change hip pain but improved most secondary outcomes. PRIMARY FUNDING SOURCE:National Health and Medical Research Council.

INTRODUCTION:Glucagon-like peptide-1 receptor agonists are known to delay gastric emptying; however, the association between glucagon-like peptide-1 receptor agonist use and peri-operative pulmonary aspiration risk is not known. This systematic review and meta-analysis aimed to summarise the evidence on whether glucagon-like peptide-1 receptor agonist exposure is associated with pulmonary aspiration or increased residual gastric content in fasted patients undergoing procedures requiring anaesthesia or sedation. METHODS:We searched six databases for studies assessing peri-operative pulmonary aspiration or residual gastric contents in fasted patients or volunteers who were using any form of glucagon-like peptide-1 receptor agonist. Pooled odds ratios were estimated for each outcome using random effects meta-analysis. Certainty of evidence for each outcome was assessed using the GRADE framework. RESULTS:Of 9010 screened studies, 28 observational studies were included. In a meta-analysis of nine studies involving 185,414 patients and 471 cases of pulmonary aspiration, glucagon-like peptide-1 receptor agonist exposure was not associated with pulmonary aspiration (OR 1.04, 95%CI 0.87-1.25, low certainty of evidence). In a meta-analysis of 18 studies involving 165,522 patients and 3831 cases of residual gastric contents, glucagon-like peptide-1 receptor agonist exposure was associated with an increased risk of residual gastric contents despite appropriate fasting (odds ratio 5.96, 95%CI 3.96-8.98, low certainty of evidence). In a meta-analysis of five studies involving 1706 patients and 208 cases of residual gastric contents, withholding at least one dose of glucagon-like peptide-1 receptor agonist before a procedure was associated with lower odds of residual gastric contents (odds ratio 0.51, 95%CI 0.33-0.81, very low certainty of evidence). DISCUSSION:Patients using glucagon-like peptide-1 receptor agonists are at increased risk of presenting for anaesthesia with residual gastric contents, though the available evidence does not indicate that this translates to an increased risk of pulmonary aspiration.

BACKGROUND:Overweight and obesity are major risk factors for non-communicable diseases (NCDs). This study aimed to explore the pattern of multimorbidity development and disease trajectories in individuals with overweight and obesity. METHODS:We followed a cohort of 392 541 individuals retrospectively from the UK Biobank. This cohort included 131 075 with normal weight (BMI 18.5-24.9 kg/m2), 169 075 with overweight (BMI 25-29.9 kg/m2), and 92 391 with obesity (BMI ≥30.0 kg/m2). Participants were followed for the diagnoses of 49 NCDs. We used Cox proportional hazards models to assess the risk of common diseases. Disease trajectory analyses were conducted to map the progression patterns of multimorbidity among individuals with overweight or obesity. RESULTS:During a median follow-up of 12.74 years, compared with individuals with normal weight, individuals with overweight had a higher risk of diagnosis of 17 NCDs, while those with obesity had 27. We identified 35 and 103 disease trajectories in individuals with overweight and obesity, among which, hypertension and cardiovascular diseases were key hub diseases. In particular, the age of disease diagnosis in individuals with obesity was younger than those with overweight, and the disease trajectory network in individuals with obesity was also 1.93 times more complex than overweight. Among identified disease trajectories, cardiometabolic diseases, including hypertension, coronary heart disease (CHD) and dyslipidemia, often appeared early, while heart failure and chronic kidney disease (CKD) appeared in a later stage of disease development. In women with obesity, depression diagnosis preceded most other multimorbidities and progressed to anxiety, painful conditions and CKD. CONCLUSION:Obesity can significantly contribute to a higher risk of multimorbidities at younger ages and with a more complex disease development trajectory than both normal weight and overweight populations. Early interventions for cardiometabolic diseases in individuals with overweight or obesity and depression in women with obesity are essential for multimorbidity management.

The obesity treatment landscape has changed markedly in the past few years following the Food and Drug Administration's approval of several highly effective obesity medications. This Perspective piece advocates for a strong focus on advancing person-centered, evidence-based obesity care at this exciting time-a time when perhaps more patients than ever before are expressing interest in obesity treatment-in order to capitalize on these innovations and ensure high-quality, compassionate, impactful patient care. Recognizing the pivotal role that clinicians play in partnering with patients to develop treatment plans, we highlight four key principles that can support clinicians' efforts in advancing these goals: (1) bias-free care, (2) education, (3) autonomy, and (4) access to care. While the obesity field is rapidly changing and both patients and providers may find it difficult to navigate treatment decisions at times, we believe that anchoring care in a person-centered, evidence-based approach may prove beneficial for all involved.

Development of safe targeted therapies for idiopathic intracranial hypertension requires a thorough understanding of recent evidence discovering the pathophysiology of the condition. The aim is to provide a review of studies that inform on the underpinning mechanisms that have been associated with idiopathic intracranial hypertension. People living with active idiopathic intracranial hypertension and obesity have been found to have with insulin resistance, hyperleptinaemia, and adverse cardiovascular outcomes. Clinically their adipose tissue is predominantly located in the truncal region and on detailed laboratory analysis the cells are primed for weight gain. There is evidence of androgen excess, altered glucocorticoid regulation and changes in pro-inflammatory cytokines. There are distinct alterations in metabolic pathways found in serum, urine and cerebrospinal fluid, that resolve following disease remission. These findings are associated with raised intracranial pressure and are likely secondary to cerebrospinal fluid hypersecretion. Idiopathic intracranial hypertension has a profile of systemic metabolic changes, endocrine dysfunction and cardiovascular risk profile distinct from that associated with obesity alone. These systemic metabolic changes are likely to contribute to dysregulation of cerebrospinal fluid dynamics, primarily hypersecretion but with a possible additional effect of reduced clearance resulting in the core feature of raised intracranial pressure.