Abd A. Tahrani

Introduction: Endoscopic bariatric therapies, including endoscopic sleeve gastroplasty (ESG) and intragastric balloon (IGB), are emerging as less invasive alternatives to bariatric surgery. However, their economic value relative to established treatments such as bariatric surgery and pharmacotherapy remains uncertain. This study evaluated the cost-effectiveness of endoscopic bariatric therapies compared with surgery and semaglutide from a UK health system perspective. Methods: Three state-transition Markov models compared: (1) ESG versus laparoscopic sleeve gastrectomy (LSG), (2) ESG versus semaglutide, and (3) IGB versus semaglutide. The models simulated transitions between body mass index (BMI)-defined health states over a 5-year time horizon using treatment effectiveness data derived from published studies and expert input. Outcomes were expressed as quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) from the UK National Health Service perspective. Deterministic and probabilistic sensitivity analyses explored uncertainty. Results: For patients with class II-III obesity, LSG was cost-effective compared with ESG (£10,593/QALY). For class I and II obesity, ESG generated modestly greater QALYs than semaglutide at slightly higher cost (ICER £7,267/QALY). Semaglutide was dominant compared with IGB, producing greater health gains at lower cost. Results were most sensitive to intervention costs and assumptions regarding long-term recurrent weight gain. Conclusions: Endoscopic bariatric therapies may represent a cost-effective option for obesity management depending on patient characteristics and comparator treatments. LSG remains the most cost-effective intervention for severe obesity, whereas ESG may offer a cost-effective alternative to pharmacotherapy for patients with lower BMI.

This narrative Review explores the role of hyperinsulinaemia as a potential independent contributor to obesity and cardiometabolic diseases. We argue that scientific discussions about the role of hyperinsulinaemia as a causal factor in these conditions have not sufficiently distinguished between postprandial insulin excursions and chronically elevated basal levels of insulin. We summarize findings from observational and experimental human trials, as well as preclinical models, and outline how reasonable evidence suggests that chronic (basal) exposure to elevated levels of insulin, rather than normal postprandial insulin excursions in isolation, might have a role in promoting or exacerbating the development of adiposity. We discuss the putative contributors to hyperinsulinaemia, including genetic predisposition, early-life influences, diet, environmental pollutants and physical inactivity, highlighting causality knowledge gaps relevant to the prevention of obesity and cardiometabolic diseases.

Background: Bariatric surgery is the most effective treatment for obesity, but access is limited. Endoscopic obesity treatments are potentially cheaper and less invasive options, which may be similarly effective. There is currently a lack of evidence to inform decisions on whether such treatments should be considered for people living with obesity. Objective(s): What is the current evidence for the clinical and cost-effectiveness of endoscopic treatments compared to alternative weight management interventions for obesity? Methods: Comprehensive searches were undertaken to January 2023 and a searchable evidence map of all quantitative studies ( n > 2) on endoscopic treatments was constructed. The map was used where possible to inform the economic models. Indirect comparisons were undertaken where relevant direct evidence for the model was not available. A systematic review of cost-effectiveness studies was undertaken. Targeted searches were undertaken to identify additional evidence to inform model parameters. Three economic (Markov) models were designed to estimate the cost-effectiveness of endoscopic therapies compared to alternative weight management interventions from a United Kingdom National Health Service and Personal Social Services perspective. Results: The evidence map included over 1500 records of studies of endoscopic therapies, most of which related to intragastric balloons and endoscopic sleeve gastrectomy. Three cost–utility analyses were identified, one of which was set in the United Kingdom and was used to inform the models. Laparoscopic sleeve gastrectomy is likely cost-effective compared with endoscopic sleeve gastroplasty for patients’ obesity class II and III (£10,593 per quality-adjusted life-year-gained). Endoscopic sleeve gastroplasty is likely cost-effective compared with semaglutide for patients’ obesity class I and II (£7267 per quality-adjusted life-year-gained). Semaglutide is dominant (cheaper and more effective) than intragastric balloon in patients’ obesity class I and II. Probabilistic sensitivity analysis found a degree of confidence in the estimates. The 5-year time horizon may not capture longer-term benefits from endoscopic sleeve gastroplasty or laparoscopic sleeve gastrectomy. Limitations and conclusions: The effectiveness evidence base was greater and more wide-ranging than anticipated. However, for the interventions compared within the economic models, there were no randomised controlled trials and either limited, or an absence of, direct comparative evidence. There was also limited long-term data on interventions. These limitations necessitated the use of assumptions in modelling. Future work: Future research should focus on longer-term effectiveness of endoscopic treatments, studies directly comparing endoscopic therapies against semaglutide or other emerging weight loss drugs and studies which better reflect the complex treatment pathways of obesity and different obesity classes. Such studies could provide more robust evidence for informing future cost-effectiveness models beyond a 5-year time horizon. Study registration: This study is registered as PROSPERO CRD42022302942. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR133099) and is published in full in Health Technology Assessment ; Vol. 29, No. 68. See the NIHR Funding and Awards website for further award information.

Background With over 1 billion individuals affected globally, obesity and obesity related diseases is now a leading cause of death. Metabolic and bariatric surgery (MBS) has emerged as a cornerstone intervention for severe obesity and its associated comorbidities. Despite its efficacy, postoperative care and follow-up after MBS remains highly variable worldwide. Objective The PARTNER study aimed to evaluate global clinical practices in the postoperative management following MBS by surveying multidisciplinary healthcare professionals. Methods This study was an international online survey conducted between October 2024 and January 2025. A multidisciplinary team developed the questionnaire based on existing literature and international guidelines. The survey assessed five domains: follow-up care, postoperative treatment, dietary management, patient support, and measurement of surgical outcomes. Responses were analysed descriptively. Results A total of 262 responses were received from 62 countries. Most respondents were bariatric surgeons (72.1%) working in public healthcare systems (73.3%). While 78.7% reported conducting three-month postoperative reviews, only 23.7% offered indefinite follow-up. Hybrid models of care (virtual and in-person) were common (56.9%). VTE prophylaxis and postoperative PPI use were recommended by 64.1% and 84.3% respectively. Nearly all respondents (98.1%) provided dietary advice, with protein and micronutrient supplementation widely endorsed. Only 56.1% routinely referred patients for psychological follow-up. Definitions of surgical success and failure varied widely, with inconsistent objective outcome measures. Conclusion The PARTNER study reveals significant international variation in postoperative management practices following MBS. These findings underscore the need for more standardized, evidence-based guidelines to improve long-term outcomes and equity of care worldwide.

Introduction A detailed understanding of the risk factors for and impacts of body mass index (BMI) progression in people living with obesity is vitally needed. In this retrospective observational study, we examined the relationships between BMI progression, obesity-related complications (ORCs) and healthcare costs in individuals living with overweight or obesity in the UK. Methods Data were from the Discover database of linked primary and secondary care records from 2.7 million individuals in North West London, UK. Included individuals were ≥ 18 years old, had a BMI of ≥ 25.0 kg/m² at index (date of first eligible BMI measurement during the study period: 1 January 2007 to 31 December 2019) and had no evidence of intentional weight loss. We examined BMI progression (increase) of ≥ 5% and ≥ 10% over 8 years in demographic and ORC subgroups, and compared ORCs and costs between groups with and without BMI progression. Results In total, 290,051 individuals were included, of whom 31.4% experienced BMI progression of ≥ 5% during follow-up, with most progression occurring from year 1 to year 3. Proportions of individuals with ≥ 5% BMI progression were highest in the following subgroups: 18–29 years (45.8%), 30–39 years (39.2%), polycystic ovary syndrome (41.4%), asthma (34.5%), depression (33.9%) and women (33.9%). Total annual healthcare costs per person per year were £1000 for those with no BMI progression, £1143 for those with 5 to < 10% progression and £1251 for those with ≥ 10% progression. Groups with progression were more likely to develop ≥ 3 ORCs than those without. Conclusion Younger adults, women and people with specific ORCs were most likely to experience BMI progression, which was associated with increased health and economic burden. Targeting high-risk subgroups with interventions to prevent weight gain could limit the clinical and economic impacts of obesity.

Introduction In this study, we aimed to quantify the economic consequences of limited access to obesity treatment and estimate the effect of modelled weight loss in a population who were eligible for bariatric surgery. Methods This was a retrospective open cohort study using data from the Discover database (1 January 2010–31 December 2019). Index was the first day that individuals were aged ≥ 18 years and eligible for bariatric surgery [body mass index (BMI) ≥ 40.0 kg/m² (obesity class III), or 35.0–39.9 kg/m² (obesity class II) and an obesity-related complication]. Time to surgery, healthcare costs and the impact of modelled weight loss over 2 years on estimated healthcare costs were assessed. Results In total, 137,184 individuals were eligible for bariatric surgery, of whom 3241 (2.4%) ultimately received surgery during follow-up. Individuals who received surgery were slightly younger, and were more likely to be women and white, than the population eligible for surgery. Overall, 36.6% of individuals underwent surgery ≥ 4 years after they became eligible. Mean annual per-person healthcare costs increased 75% between year 1 and year 8 of the period before surgery in this group [from 1150 British pound sterling (GBP) to 2013 GBP]. Modelled weight loss of 10% would result in 58.3% of eligible individuals transitioning to obesity class I after 2 years, with only 12.2% remaining in obesity class III, resulting in a 14.3% reduction in healthcare costs. Greater degrees of weight loss were associated with greater estimated reductions in BMI and cost. Conclusion Delays to prompt weight management support appear to be associated with increasing healthcare costs, which could be mitigated by improving access to weight management.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways. Several proteins were regulated with semaglutide, after accounting for changes in body weight and HbA_1c at end of trial, suggesting effects of semaglutide on the proteome beyond weight loss and glucose lowering. A comparison of semaglutide with real-world proteomic profiles revealed potential benefits on disease-specific proteomic signatures including the downregulation of specific proteins associated with cardiovascular disease risk, supporting its reported effects of lowering cardiovascular disease risk and potential drug repurposing opportunities. This study showcases the potential of proteomics data gathered from randomized trials for providing insights into disease mechanisms and drug repurposing opportunities. These data also highlight the unmet need for, and importance of, examining proteomic changes in response to weight loss pharmacotherapy in future trials.

Cardiovascular autonomic neuropathy (CAN) is an under-recognised yet highly prevalent microvascular complication of diabetes. CAN affects approximately 20% of people with diabetes, with recent studies highlighting the presence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose), indicating early involvement of the autonomic nervous system. Understanding of the pathophysiology of CAN continues to evolve, with emerging evidence supporting a potential link between lipid metabolites, mitochondrial dysfunction and genetics. Recent advancements, such as streamlining CAN detection through wearable devices and monitoring of heart rate variability, present simplified and cost-effective approaches for early CAN detection. Further research on the optimal use of the extensive data provided by such devices is required. Despite the lack of specific pharmacological interventions targeting the underlying pathophysiology of autonomic neuropathy, several studies have suggested a favourable impact of newer glucose-lowering agents, such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists, where there is a wealth of clinical trial data on the prevention of cardiovascular events. This review delves into recent developments in the area of CAN, with emphasis on practical guidance to recognise and manage this underdiagnosed condition, which significantly increases the risk of cardiovascular events and mortality in diabetes. Graphical Abstract

Osteoarthritis (OA) is increasing in prevalence and has a severe impact on patients’ lives. However, our understanding of biomarkers driving OA risk remains limited. We developed a model predicting the five-year risk of OA diagnosis, integrating retrospective clinical, lifestyle and biomarker data from the UK Biobank (19,120 patients with OA, ROC-AUC: 0.72, 95%CI (0.71–0.73)). Higher age, BMI and prescription of non-steroidal anti-inflammatory drugs contributed most to increased OA risk prediction ahead of diagnosis. We identified 14 subgroups of OA risk profiles. These subgroups were validated in an independent set of patients evaluating the 11-year OA risk, with 88% of patients being uniquely assigned to one of the 14 subgroups. Individual OA risk profiles were characterised by personalised biomarkers. Omics integration demonstrated the predictive importance of key OA genes and pathways (e.g., GDF5 and TGF-β signalling) and OA-specific biomarkers (e.g., CRTAC1 and COL9A1). In summary, this work identifies opportunities for personalised OA prevention and insights into its underlying pathogenesis.