The Future of Endobariatrics: Bridging the Gap.

With the growing global burden of obesity, the field of endobariatrics has emerged as a promising alternative, filling the void between lifestyle interventions with modest efficacy and more invasive surgical procedures. This article explores the latest advancements in endobariatric therapies, encompassing endoscopic sleeve gastroplasty (ESG), intragastric balloons (IGB), endoscopic metabolic therapies, and promising pharmacologic and surgical combination approaches that integrate multiple therapeutic modalities. It also outlines the critical factors and strategic considerations necessary for the successful integration of endobariatric interventions into clinical practice.

Randomized Controlled Trial Based US Commercial Payor Cost-Effectiveness Analysis of Endoscopic Sleeve Gastroplasty Versus Lifestyle Modification Alone for Adults With Class I/II Obesity.

PURPOSE: Endoscopic sleeve gastroplasty (ESG) is a minimally invasive day procedure that the MERIT randomized controlled trial (RCT) has demonstrated to be an effective and safe method of weight loss versus lifestyle modification alone. We sought to evaluate the cost-effectiveness of ESG from the perspective of a US commercial payer in a cohort of adults with class II and class I obesity with diabetes based on this RCT. MATERIALS: We used a Markov modelling approach with BMI group health states and an absorbing death state. Baseline characteristics, utilities, BMI group transition probabilities, and adverse events (AEs) were informed by patient-level data from the MERIT RCT. Mortality was estimated by applying BMI-specific hazard ratios to US general population mortality rates. We used BMI-based health state utilities to reflect the impact of obesity comorbidities and applied disutilities due to ESG AEs. Costs included intervention costs, AE costs, and BMI-based annual direct healthcare costs to account for costs associated with obesity comorbidities. A willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was assumed. RESULTS: In our base-case analysis over a 5-year time horizon, ESG was cost-effective versus lifestyle modification alone with an incremental cost-effectiveness ratio of $23,432/QALY. ESG remained cost-effective in all sensitivity analyses we conducted and was dominant in analyses with longer time horizons. CONCLUSION: ESG is a cost-effective treatment option for people living with obesity and should be considered in commercial health plans as an additional treatment option for clinically eligible patients.

Navigating the Predictive Landscape: DiaRem's Role in Unveiling Outcomes for Diabetes Remission following ESG.

PURPOSE: Rising obesity and type 2 diabetes mellitus (T2DM) rates can be mitigated by various strategies, with a 10% total body weight loss (TBWL) threshold often required for T2DM remission. T2DM remission rates after bariatric surgery like Roux-en-Y gastric bypass (RYGB) are well established; endoscopic sleeve gastroplasty (ESG) is a less invasive option that averages 15% TBWL and allows for T2DM remission. This study explores the DiaRem (Diabetes Remission post-RYGB) score's ability to predict T2DM remission 1-year post-ESG. MATERIALS AND METHODS: We conducted a retrospective cohort study on 39 individuals with T2DM who underwent ESG. Age, utilization of diabetes medications, insulin administration, and hemoglobin A1c levels were used to calculate the DiaRem score. The area under the receiver operating characteristic curve (AUC) was employed to evaluate the discriminative ability of DiaRem in distinguishing diabetes remission. RESULTS: Among the 39 patients with a median hemoglobin A1c of 6.7, 12.8% required insulin, and 43.6% used diabetes medication. At 1-year post-ESG, 69.2% of patients experienced diabetes remission with a median %TWBL of 12.7. The DiaRem score's ability to detect diabetes resolution for ESG patients had a sensitivity of 100% and a specificity of 58.3%, at the optimal cutoff value of 10. The AUC was 0.779 (95% CI 0.546-0.959). CONCLUSION: Our study demonstrated the DiaRem score's predictive value for T2DM remission post-ESG, highlighting its utility in clinical decision-making for ESG-related outcomes. Further investigation is needed to identify alternative indicators that may enhance predictive accuracy, thus refining personalized decision-making for this patient group.

Endoscopic Ultrasound-guided Jejunocolostomy for Management of Refractory Severe Obesity in a Post-gastric Bypass Patient.

Obesity is a complex disease process, which often requires multifactorial, patient-tailored strategies for effective management. Treatment options include lifestyle optimization, pharmacotherapy, endobariatrics, and bariatric metabolic endoscopy. Obesity-based interventions can be challenging in patient populations with severe obesity, particularly post-gastric bypass. We report the case of a non-surgical patient with a failed remote open gastric bypass, who underwent an endoscopic small bowel diversion procedure, resulting in partial caloric diversion, via the creation of an EUS-guided jejunocolostomy (EUS-JC). The procedure is an extension of prior reported EUS-guided and magnet-based small bowel bypass procedures, in this case, for the purposes of weight loss (Kahaleh et al., 1; Jonica et al. Gastrointest Endosc. 97(5):927-933, 2; Machytka et al. Gastrointest Endosc. 86(5):904-912, 3;). The procedure was performed without peri-procedural complications, with effective weight loss during follow-up. Endoscopic bariatric interventions that target the small bowel, such as EUS-JC, offer promising tools for obesity management and should be studied further. Numerous factors including lifestyle, psychosocial, genetic, behavioral, and secondary disease processes contribute to obesity. Severe obesity (defined as a BMI > 50 kg/m2) is associated with increased morbidity and mortality with a significantly reduced response to treatment (Flegal et al. JAMA. 309(1):71-82, 4;). Weight regain can be noted in up to 50% of patients post-RYGB. In populations with severe obesity, there is an associated 5-year surgical failure rate of 18% (Magro et al. Obesity Surg. 18(6):648-51, 5;). These patients may not be surgical candidates for revision or can develop post-revision chronic protein-caloric malnutrition (Shin et al. Obes Surg. 29(3):811-818, 6;). Lifestyle, modification, pharmacotherapy, or endoscopic transoral reduction (TORe) can be effective generally; however, in patients with severe obesity, the total desired excess body weight loss may not likely be accomplished solely by these strategies. An endoscopic small bowel intervention that diverts a portion of caloric intake from small bowel absorption can potentially promote weight loss similar to a surgical lengthening of the Roux limb (Shah et al. Obes Surg. 33(1):293-302, 7; Hamed et al. Annal Surg. 274(2):271-280, 8;), in the sense that there is a reduction in the total small bowel surface area for absorption. Roux limb distalization can be effective for weight regain for post bypass patients. The EUS-JC technique aims to work similarly by reducing the total small bowel surface area utilized for absorption. Since this patient was deemed a non-surgical candidate, an EUS-guided jejunocolostomy was offered. Prior to the procedure, the patient established longitudinal care with our bariatric nutritionist and obesity medicine services. Extensive pre-bariatric labs were screened to rule out confounders for recurrent severe obesity. Intra-procedure, the patient received one dose of 500 mg intravenous levofloxacin. Post-procedure, loperamide was prescribed every 8 h as needed for post-procedure diarrhea. Within 2 weeks, the patient was no longer taking anti-diarrheals. The post-procedure diet consisted of a liquid diet for 2 days before advancement to a low-residue diet for 1 month, and then a regular diet.

Endoscopic Ultrasound-guided Transmural Biliary Drainage With 6 mm and 8 mm Cautery-enhanced Lumen-apposing Metal Stents: A Multicenter Collaborative Study.

OBJECTIVE: Endoscopic retrograde cholangiopancreatography (ERCP) may be unsuccessful in patients with duodenal stenosis or malignant ampullary infiltration. Endoscopic ultrasound-guided biliary drainage (EUS-BD) has been proposed as an alternative. We aimed to assess the efficacy and safety of EUS-BD for malignant distal bile duct obstruction using the newly introduced smaller caliber 6 or 8 mm cautery-enhanced lumen-apposing metal stent. METHODS: A multicenter retrospective study was performed on patients with unresectable malignant distal bile duct obstruction who underwent EUS-BD between 2021 and 2022 after unsuccessful ERCP. RESULTS: Thirty-two patients were included [7 (53.13%) males], with a mean age of 72.2 ± 12.5 years. The technical success rate was 100%. Altered anatomy was present in 2 (6.25%). The indication for drainage was biliary obstruction from pancreatic cancer in 26 patients (84.5%), cholangiocarcinoma in 3 (9.4%), and ampullary mass in 3 (9.4%). The procedure was performed mostly in an outpatient setting (n = 19, 59.38%). The clinical success rate was 92.3% [bilirubin: 14.1 (SD: 8.9) preprocedure vs 4.9 (SD: 1.1) postprocedure; P = 0.0001]. There was one early adverse event of a perforation, which was closed endoscopically and drained percutaneously. Delayed adverse events included food impaction of the stent (n = 1), which was resolved with a repeat procedure and insertion of a double pigtail stent. CONCLUSION: This study demonstrates the feasibility of EUS-BD drainage using smaller caliber 6 or 8 mm lumen-apposing metal stent to relieve malignant distal bile duct obstruction in patients who fail conventional ERCP.

Risk of Pancreatitis After Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Pancreatic Cystic Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is frequently used to risk-stratify pancreatic cystic lesions (PCLs). Rising PCL incidence and developments in tissue acquisition and specimen analysis necessitate updated appraisal of EUS-FNA safety, particularly the risk of postprocedure pancreatitis, the most common EUS-FNA-related adverse event. Our systematic review aims to accurately quantify the risk of EUS-FNA-related pancreatitis to best inform decisions regarding EUS-FNA's optimal role in PCL workup. METHODS: We performed systematic searches in 4 databases from inception to April 2024 for original English-language studies investigating EUS-FNA-related pancreatitis. We extracted data on demographics and EUS-FNA-related pancreatitis risk, severity, and risk factors. These were meta-analyzed through the DerSimonian Laird Method using a random-effects model. Meta-regression of pancreatitis risk was performed to delineate associations with clinical and procedural characteristics. RESULTS: Sixty-four studies comprised 8,086 patients and reported 110 EUS-FNA-related pancreatitis events. Pooled risk of EUS-FNA-related pancreatitis was 1.4% (95% confidence intervals, -0.8% to 3.5%; I2 = 0.00), which was predominantly of mild severity (67%) and uniformly nonfatal. Pancreatitis risk lacked significant association with sample size, age, sex, cyst size, needle caliber, or passes, although we noted trends toward higher risk in studies published after 2015, those using higher gauge needles (19 G vs 22 G/25 G), and those performing EUS-guided through-the-needle biopsy. DISCUSSION: We note with high certainty that pancreatitis after EUS-FNA of PCLs is infrequent and mild in severity with no mortality in the included cohort. EUS-guided through-the-needle biopsy may serve as a significant risk factor for EUS-FNA-related pancreatitis risk; however, further studies are needed to delineate other predisposing characteristics.

New-Onset Type 2 Diabetes after Bariatric Surgery: A Matched Cohort Study.

INTRODUCTION: The objective of this study is to determine the difference in rates of new-onset type 2 diabetes (T2D) for individuals who have had metabolic and bariatric surgery (MBS) and similar individuals who did not have MBS, and to determine whether differences in new-onset T2D differ depending on whether the individual had prediabetes at baseline. METHODS: This study used data from a large United States employer-based retrospective claims database from 2016 to 2021 (analysis completed in 2023). Individuals who did and did not have MBS were matched 1:1 on index year, sex, age, health plan type, region, body mass index, baseline healthcare costs, other obesity-related comorbidities, prediabetes diagnosis, and inpatient admissions in the year before the index date. New-onset T2D was examined at 1 (18,752 matches) and 3 (5,416 matches) years after the index date and stratified by baseline prediabetes. RESULTS: Among the full cohort of individuals with and without prediabetes at baseline, 0.1% and 2.7% of individuals who had did and did not have MBS developed T2D within 1 year after the index date, respectively (difference=2.6, 95% CI 2.4-2.8), and 0.3% and 8.4% of individuals who did and did not have MBS developed T2D within 3 years after the index date, respectively (difference=8.1, 95% CI 7.3-8.8). The difference in new-onset T2D was greatest among individuals with prediabetes at baseline. CONCLUSIONS: This study demonstrated patients with obesity and without T2D who undergo MBS are significantly less likely to develop new-onset T2D compared to matched non-MBS patients.

Practice patterns and outcomes of endoscopic sleeve gastroplasty based on provider specialty.

Background and study aims Endoscopic sleeve gastroplasty (ESG) is performed in clinical practice by gastroenterologists and bariatric surgeons. Given the increasing regulatory approval and global adoption, we aimed to evaluate real-world outcomes in multidisciplinary practices involving bariatric surgeons and gastroenterologists across the United States. Patients and methods We included adult patients with obesity who underwent ESG from January 2013 to August 2022 in seven academic and private centers in the United States. Patient and procedure characteristics, serious adverse events (SAEs), and weight loss outcomes up to 24 months were analyzed. SPSS (version 29.0) was used for all statistical analyses. Results A total of 1506 patients from seven sites included 235 (15.6%) treated by surgeons and 1271 (84.4%) treated by gastroenterologists. There were no baseline differences between groups. Gastroenterologists used argon plasma coagulation for marking significantly more often than surgeons ( P <0.001). Surgeons placed sutures in the fundus in all instances whereas gastroenterologist placed them in the fundus in less than 1% of the cases ( P <0.001>). Procedure times were significantly different between groups, with surgeons requiring approximately 20 minutes more during the procedure than gastroenterologists ( P <0.001). Percent total body weight loss (%TBWL) and percent responders achieving >10 and >15% TBWL were similar between the two groups at 12, 18, and 24 months. Rates of SAEs were low and similar at 1.7% for surgeons and 2.7% for gastroenterologists ( P >0.05). Conclusions Data from a large US cohort show significant and sustained weight loss with ESG and an excellent safety profile in both bariatric surgery and gastroenterology practices, supporting the scalability of the procedure across practices in a multidisciplinary setting.

Efficacy, Feasibility, and Safety of the X-Tack Endoscopic HeliX Tacking System: A Multicenter Experience.

BACKGROUND AND AIMS: The application of endoscopic suturing has revolutionized defect closures. Conventional over-the-scope suturing necessitates removal of the scope, placement of the device, and reinsertion. A single channel, single sequence, through-the-scope suturing device has been developed to improve this process. This study aims to describe the efficacy, feasibility, and safety of a through-the-scope suturing device for gastrointestinal defect closure. METHODS: This was a retrospective multicenter study involving 9 centers of consecutive adult patients who underwent suturing using the X-Tack Endoscopic HeliX Tacking System (Apollo Endosurgery). The primary outcomes were technical success and long-term clinical success. Secondary outcomes included adverse events, recurrence, and reintervention rates. RESULTS: In all, 56 patients (mean age 53.8, 33 women) were included. Suturing indications included fistula repair (n=22), leak repair (n=7), polypectomy defect closure (n=12), peroral endoscopic myotomy (POEM) site closure (n=7), perforation repair (n=6), and ulcers (n=2). Patients were followed at a mean duration of 74 days. Overall technical and long-term clinical success rates were 92.9% and 75%, respectively. Both technical and clinical success rates were 100% for polypectomies, POEM-site closures, and ulcers. Success rates were lower for the repair of fistulas (95.5% technical, 54.5% clinical), leaks (57.1%, 28.6%), and perforations (100%, 66.7%). No immediate adverse events were noted. CONCLUSION: This novel, through-the-scope endoscopic suturing system, is a safe and feasible method to repair defects that are ≤3 cm. The efficacy of this device may be better suited for superficial defects as opposed to full-thickness defects. Larger defects will need more sutures and probably a double closure technique to provide a reinforcement layer.

Outcomes of Endoscopic Ultrasound-guided Fine Needle Biopsy Using a Novel Hydrostatic Stylet Tissue Acquisition Technique.

BACKGROUND: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is frequently used to obtain core samples of solid lesions. Here, we describe and evaluate a novel hydrostatic stylet (HS) technique designed to optimize core sample acquisition, reporting diagnostic yield, efficacy, and safety relative to the conventional stylet slow-pull (SP) technique. METHODS: A novel HS technique was developed and validated retrospectively. Consecutive patients who underwent EUS-FNB with core biopsy of solid lesions through either the HS or SP technique between January 2020 and April 2022 were included. Exclusion criteria included cystic lesions, nonlesional liver biopsies, and specimens sent for cytologic analysis only. Patient and lesion characteristics, number of passes, sample adequacy, and adverse events were compared between the two techniques. RESULTS: A total of 272 patients were included with 138 in the HS group and 134 in the SP group. Lesion size and anatomic distribution were similar in both groups. Compared with the SP approach, the HS technique demonstrated significantly higher sample adequacy (97.8% vs 83.6%, P < 0.001), higher sensitivity (97.1% vs 89.7%, P = 0.03), and lower mean number of passes (1.2 vs 3.3, P < 0.001). Rates and severity of adverse events in the HS group were comparable to the SP group and existing literature. Similar associations were observed in pancreatic and nonpancreatic lesion subanalyses. CONCLUSIONS: The novel HS technique demonstrated excellent biopsy sample adequacy and diagnostic yield while requiring fewer passes to obtain diagnostic specimens compared with a conventional EUS-FNB approach. Further prospective evaluation is needed to confirm these pilot findings and optimize EUS-FNB acquisition techniques.

Updates in metabolic bariatric endoscopy.

Obesity and its associated comorbid conditions have been increasing globally. Endoscopic bariatric and metabolic therapies (EBMTs) were initially designed to replicate bariatric surgery physiology for those who are not or choose not to be surgical candidates. Now, newer procedures target the complicated pathophysiology underlying obesity and its comorbidities. EBMT has been categorized based on its therapeutic target (stomach or small intestine), but innovations have expanded to include extraintestinal organs including the pancreas. Gastric EBMTs, namely space-occupying balloons, gastroplasty with suturing or plication, and aspiration therapy, are primarily used for weight loss. Small bowel EBMTs are designed to cause malabsorption, epithelial endocrine remodeling, and other changes to intestinal physiology to ultimately improve the metabolic comorbidities of obesity rather than induce weight loss alone. These include duodenal mucosal resurfacing, endoluminal bypass sleeves, and incisionless anastomosis systems. Extraluminal or pancreatic EBMT is aimed to restore the production of normal pancreatic proteins that are involved in the progression of type 2 diabetes. This review discusses the current and new technologies of metabolic bariatric endoscopy, their pros and cons, and areas for future research.

Preferred techniques for endoscopic ultrasound-guided gastroenterostomy: a survey of expert endosonographers.

Background and study aims Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is an emerging procedure that lacks technical standardization with limited adoption beyond expert centers. We surveyed high-volume endosonographers about the technical aspects of EUS-GE to describe how the procedure is currently performed at expert centers and identify targets for standardization. Methods Invitations to complete an electronic survey were distributed to 21 expert EUS practitioners at 19 U.S. centers. Respondents were surveyed about technical aspects of EUS-GE, indications, efficacy, safety, and attitudes toward the procedure. Results All 21 (100%) invited expert endoscopists completed the survey. Nine (42.9%) reported performing >10 EUS-GEs in the last 12 months. About half (47.6%, 10/21) puncture the target loop prior to lumen-apposing metal stent (LAMS) introduction, most often to confirm the loop is jejunum. No respondents reported guidewire placement prior to LAMS introduction. Most (71.4%, 15/21) do not use a guidewire at any time, while 28.6% (6/21) reported wire placement after distal flange deployment to secure the tract during apposition. Eight (38.1%, 8/21) reported at least one major adverse event, most commonly intraperitoneal LAMS deployment (87.5%, 7/8). Factors most often reported as advantageous for EUS-GE over enteral stenting included lack of papilla interference (33.3%, 7/21) and decreased occlusion risk (23.8%, 5/21). Conclusions Significant variation in performance technique for EUS-GE exists among expert US endoscopists, which may hinder widespread adoption and contribute to inconsistencies in reported patient outcomes. The granularity provided by these survey results may identify areas to focus standardization efforts and guide future studies on developing an ideal EUS-GE protocol.

Methodology and Results of a Joint IFSO-WGO Delphi Survey of 94 Intercontinental, Interdisciplinary Experts in Obesity Management.

BACKGROUND: Obesity affects 1.5 billion people worldwide, yet few are treated effectively and considerable variability exists in its management. In 2020, a joint International Federation of Surgery for Obesity and Metabolic Diseases (IFSO) and World Gastroenterology Organization (WGO) advisory committee initiated the drafting of consensus guidelines on obesity management, to be based on detailed literature reviews and the results of an extensive multi-disciplinary survey of intercontinental experts. This paper reports on the latter. The objective of this study is to identify areas of consensus and non-consensus among intercontinental, inter-disciplinary experts in obesity management. METHODS: Guided by an international consensus-survey expert, a three-round online Delphi survey was conducted in the summer of 2021 of international obesity-management experts spanning the fields of medicine, bariatric endoscopy and surgery, psychology, and nutrition. Issues like epidemiology and risk factors, patient selection for metabolic and bariatric surgery (ASMBS-Clinical-Issues-Committee, Surg Obes Relat Dis : Off J Am Soc Bariatric Surg. 8:e27-32, 1), psychological issues, patient preparation for MBS, bariatric endoscopy, and outcomes and follow-up were addressed. RESULTS: Ninety-four experts from six continents voted on 180 statements, with consensus reached on 158, including consensus agreement with 96 and disagreement with 24 statements (38 had other response options besides agree/disagree). Among unanimous opinions were the need for all medical societies to work together to address obesity, for regular regional and national obesity surveillance, for multi-disciplinary management, to recognize the increasing impact of childhood and adolescent obesity, to accept some weight regain as normal after MBS, and for life-long follow-up of MBS patients. CONCLUSIONS: Obesity is a major health issue that requires aggressive surveillance and thoughtful multidisciplinary management.

Type 2 Diabetes Remission After Bariatric Surgery and Its Impact on Healthcare Costs.

PURPOSE: Bariatric surgery is the most effective and durable treatment of obesity and can put type 2 diabetes (T2D) into remission. We aimed to examine remission rates after bariatric surgery and the impacts of post-surgical healthcare costs. MATERIALS AND METHODS: Obese adults with T2D were identified in Merative™ (US employer-based retrospective claims database). Individuals who had bariatric surgery were matched 1:1 with those who did not with baseline demographic and health characteristics. Rates of remission and total healthcare costs were compared at 6-12 and 6-36 months after the index date. RESULTS: Remission rates varied substantially by baseline T2D complexity; differences in rates at 1 year ranged from 41% for those with high-complexity T2D to 66% for those with low- to mid-complexity T2D. At 3 years, those who had bariatric surgery had 56% higher remission rates than those who did not have bariatric surgery, with differences of 73%, 59%, and 35% for those with low-, mid-, and high-complexity T2D at baseline. Healthcare costs were $3401 and $20,378 lower among those who had bariatric surgery in the 6 to 12 months and 6 to 36 months after the index date, respectively, than their matched controls. The biggest cost differences were seen among those with high-complexity T2D; those who had bariatric surgery had $26,879 lower healthcare costs in the 6 to 36 months after the index date than those who did not. CONCLUSION: Individuals with T2D undergoing bariatric surgery have substantially higher rates of T2D remission and lower healthcare costs.

Radiofrequency ablation for pancreatobiliary disease: an updated review.

Endoscopic radiofrequency ablation (RFA) has emerged as a minimally invasive treatment option in cases of malignant biliary obstruction, pancreatic cancer, and other pancreatic cystic neoplasms. Intraductal biliary RFA is safe, effective, and confers a survival advantage over stenting alone, where it should be used an adjunct to biliary stenting. Endoscopic ultrasound-guided RFA can also provide pancreatic cyst resolution in patients who are not ideal operative candidates. The aim of this review is to describe the endoscopic applications and associated outcomes of RFA.

Cost-effectiveness of endoscopic, surgical and pharmacological obesity therapies: a microsimulation and threshold analyses.

OBJECTIVE: Weight loss interventions to treat obesity include sleeve gastrectomy (SG), lifestyle intervention (LI), endoscopic sleeve gastroplasty (ESG) and semaglutide. We aimed to identify which treatments are cost-effective and identify requirements for semaglutide to be cost-effective. DESIGN: We developed a semi-Markov microsimulation model to compare the effectiveness of SG, ESG, semaglutide and LI for weight loss in 40 years old with class I/II/III obesity. Extensive one-way sensitivity and threshold analysis were performed to vary cost of treatment strategies and semaglutide adherence rate. Outcome measures were incremental cost-effectiveness ratios (ICERs), with a willingness-to-pay threshold of US$100 000/quality-adjusted life-year (QALY). RESULTS: When strategies were compared with each other, ESG was cost-effective in class I obesity (US$4105/QALY). SG was cost-effective in class II obesity (US$5883/QALY) and class III obesity (US$7821/QALY). In class I/II/III, obesity, SG and ESG were cost-effective compared with LI. However, semaglutide was not cost-effective compared with LI for class I/II/III obesity (ICER US$508 414/QALY, US$420 483/QALY and US$350 637/QALY). For semaglutide to be cost-effective compared with LI, it would have to cost less than US$7462 (class III), US$5847 (class II) or US$5149 (class I) annually. For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US$1879 (class III), US$1204 (class II) or US$297 (class I) annually. CONCLUSIONS: Cost-effective strategies were: ESG for class I obesity and SG for class II/III obesity. Semaglutide may be cost-effective with substantial cost reduction. Given potentially higher utilisation rates with pharmacotherapy, semaglutide may provide the largest reduction in obesity-related mortality.