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Brain and Cardiometabolic Effects of Major Weight Loss in People With Obesity: Preliminary Cohort Findings

Gaggi, Naomi L; Hurwitz, Brian; Bernal, Jennifer; O'Brien, Courtney; Ren-Fielding, Christine; Lofton, Holly; Chen, Jenny; Saperstein, Aviezer; Lee, Sang Han; Chang, Yun-Juan; Yates, Kathy F; Fieremans, Els; Osorio, Ricardo; Convit, Antonio
OBJECTIVE/UNASSIGNED:Given the overlap between obesity-related metabolic and vascular abnormalities and Alzheimer's disease (AD) risk factors, it is critical to determine whether weight loss improves brain and cardiovascular health. This study examined whether ≥ 40% excess-weight loss is associated with improvements in cardiometabolic risk, brain structure, and cognition. METHODS/UNASSIGNED:The study was a longitudinal study of individuals with obesity undergoing metabolic and bariatric surgery or medical/behavioral weight-loss treatment. Participants were classified at follow-up as weight-loss (WL; ≥ 40% excess-weight loss) or non-weight-loss (nWL; < 40%). All completed medical evaluations, structural MRI, and cognitive testing at baseline and 1 year. RESULTS/UNASSIGNED:At 1 year, the WL group exhibited improvements in BMI, HbA1C, inflammatory, metabolic, and lipid profiles. MRI-based volumetrics revealed increases in subcortical gray-matter volume and preservation of AD-vulnerable regions. Cognitive performance remained unchanged. CONCLUSIONS/UNASSIGNED:Achieving ≥ 40% excess-weight loss was associated with improvements in metabolic health and brain structure, including favorable subcortical volume increases. These findings underscore the potential of sustained weight reduction to mitigate risks linked to metabolic syndromes and neurodegeneration. Longer-term follow-up is warranted to determine whether continued metabolic improvements lead to detectable cognitive gains and additional brain-health benefits beyond 1 year.
PMCID:13720752
PMID: 42964797
ISSN: 2055-2238
CID: 6074823

Metabolic bariatric surgery versus GLP-1 receptor agonists in dialysis patients with diabetes and obesity: a target trial emulation study

Gao, Chenxi; Menon, Gayathri; Chen, Yusi; Li, Yiting; Bae, Sunjae; Lonze, Bonnie E; Ren-Fielding, Christine J; Chhabra, Karan R; Segev, Dorry L; McAdams-DeMarco, Mara A; Orandi, Babak J
BACKGROUND:Metabolic and bariatric surgery (MBS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective treatments for obesity and type 2 diabetes, but their comparative survival and waitlisting benefits in end-stage kidney disease (ESKD) remain unclear. OBJECTIVES/OBJECTIVE:To compare survival and kidney transplant (KT) waitlisting after MBS and GLP-1RA use among patients with ESKD, using dipeptidyl peptidase-4 inhibitors (DPP-4is) as an active comparator. SETTING/METHODS:US Renal Data System, 2010-2022. METHODS:We included adults with ESKD, type 2 diabetes, and ≥class II obesity treated with MBS, GLP-1RA, or DPP-4i. Three target trials were emulated: MBS versus GLP-1RA (N = 1818), MBS versus DPP-4i (N = 2111), and GLP-1RA versus DPP-4i (N = 4338). Cox models estimated adjusted hazard ratios (aHRs) for all-cause mortality and KT waitlisting over 1-5 years. RESULTS:MBS recipients were younger at dialysis initiation than matched GLP-1RA and DPP-4i users. MBS was associated with higher short-term mortality than matched GLP-1RA (1-year aHR = 2.68, 95% confidence interval [CI]:1.98-3.63; 3-year aHR = 1.34, 95% CI: 1.09-1.64) and DPP-4i users (1-year aHR = 1.74, 95% CI: 1.35-2.25), but comparable longer-term mortality. GLP-1RA users had consistently lower mortality than matched DPP-4i users. MBS was associated with higher KT waitlisting than GLP-1RA and DPP-4i use, with no differences between GLP-1RA and DPP-4i users. CONCLUSIONS:Among patients with ESKD, type 2 diabetes, and obesity, MBS was associated with higher short-term but comparable long-term mortality, whereas GLP-1RA use was associated with lower mortality than DPP-4i use. MBS was also associated with higher KT waitlisting than GLP-1RA and DPP-4i use, suggesting distinct risk-benefit profiles of metabolic treatment in this high-risk population.
PMID: 42907282
ISSN: 1878-7533
CID: 6074898

Management of portomesenteric vein thrombosis following bariatric surgery

Kozato, Akio; Hickey, Ryan M; Hindman, Nicole; Cuva, Dylan; Khondaker, Sabrina; Vu, Alexander Hien; Sy, Shane Francheska; Park, Julia; Chui, Patricia; Peacock, Matthew; Freitas, Derek; Saunders, John K; Lipman, Jeffrey; Orandi, Babak J; Massie, Allan B; Ren-Fielding, Christine; Ude Welcome, Akuezunkpa O; Chopra, Ajay K; Parikh, Manish; Chhabra, Karan R
BACKGROUND:Portomesenteric venous thrombosis (PMVT) is a rare complication of bariatric surgery that can lead to cavernous transformation of the portal vein. There are no established treatment algorithms regarding anticoagulation (AC) only vs. catheter-directed thrombolysis in this population. METHODS:Medical records at 4 urban bariatric surgery centers were queried for patients diagnosed with PMVT between 2012 and 2025. Patient characteristics, perioperative details, imaging at PMVT diagnosis, treatment course, and follow-up imaging were reviewed. Fisher's exact testing was conducted to identify correlations between extent of thrombosis, treatment course (anticoagulation vs. interventional radiology [IR] thrombolysis), and the outcome of cavernous transformation. RESULTS:71 patients were diagnosed with PMVT following bariatric surgery (68 LSG, 3 RYGB) at 4 centers between 2012 and 2025. Median time from surgery to PMVT diagnosis was 13 days. Three patients (4%) required reoperation for small bowel resection, of whom 2 underwent open thrombectomy and 1 underwent subsequent IR thrombolysis. Of the remaining patients, 6/68 (9%) underwent IR catheter-directed thrombolysis, and 62/68 (91%) received AC only. Of 53 patients with long-term data, 18 (34%) developed cavernous transformation. Among patients who had a main portal vein + intrahepatic portal vein + inflow (superior mesenteric vein or splenic vein) thrombosis, treatment with AC only was strongly associated with cavernous transformation (13/17, 76%) vs IR (1/5, 20%, p < 0.05). There were no deaths related to PMVT. CONCLUSIONS:In this largest known case series of postbariatric surgery PMVT treated with anticoagulation vs. IR, we found that the PMVT clot pattern with the highest risk of developing cavernous transformation was the extensive type involving the main portal vein, an intrahepatic portal vein, and an inflow vein, whether the main portal vein clot was occlusive or nonocclusive. Early IR intervention was associated with decreased cavernous transformation.
PMID: 42629487
ISSN: 1432-2218
CID: 6071524

Evolving utilization of bariatric surgery since the rise of semaglutide and tirzepatide

Kozato, Akio; Patel, Suhani S; Orandi, Babak J; Massie, Allan B; Mankowski, Michal; Ren-Fielding, Christine; Segev, Dorry L; Parikh, Manish; Chhabra, Karan R
BACKGROUND:Semaglutide and tirzepatide have transformed obesity treatment, but recent changes to bariatric surgery utilization are not well understood. METHODS:Epic's nationwide Cosmos database was queried for patients who underwent primary sleeve gastrectomy or gastric bypass between 2018 and 2025. Patient characteristics including preoperative semaglutide or tirzepatide dispense history were compared using chi-squared and Wilcoxon rank sum tests. Modified Poisson regression was used to identify factors independently associated with pre-surgery GLP-1RA use. Multilevel models were used to examine hospital- and state-level variation in pre-surgery GLP-1RA use. RESULTS:Bariatric surgery utilization increased after Q3 2018, peaked in Q4 2022, and subsequently decreased 39% through Q4 2025. Between Q4 2018 and Q4 2025, the proportion of Hispanic bariatric surgery patients increased (8.1% vs. 16.8%, p < 0.001), and the proportion of patients who received pre-surgery GLP-1RA increased (0.2% vs. 35.3%, p < 0.001). Factors associated with receiving pre-surgery GLP-1RA were year, private insurance, White race, type 2 diabetes (RR 2.94 [2.88-3.00]), older age, sleep apnea, and metabolic dysfunction-associated steatotic liver disease. Factors associated with receiving surgery upfront were Hispanic ethnicity, Black race, and public or no insurance. After adjusting for patient characteristics and year, there was a 15-fold difference in pre-surgery GLP-1RA use between the highest and lowest hospitals (RR 0.19-2.88). CONCLUSIONS:In the Epic Cosmos database, bariatric surgery utilization decreased from 2022 to 2025, and those who underwent bariatric surgery increasingly received GLP-1RA before surgery. Patients who received pre-surgery GLP-1RA were older, White, privately insured, with diabetes and other weight-related comorbidities, while patients who received surgery upfront were Hispanic, Black, and publicly insured. Pre-surgery GLP-1RA use was also driven by center-specific non-clinical factors.
PMID: 42467193
ISSN: 1432-2218
CID: 6067402

Conversion of endoscopic sleeve gastroplasty to bariatric surgery

Kozato, Akio; Khondaker, Sabrina; Hindman, Nicole; Park, Julia; Chui, Patricia; Peacock, Matthew; de Latour, Rabia; Freitas, Derek; Saunders, John K; Lipman, Jeffrey; Orandi, Babak J; Ren-Fielding, Christine; Parikh, Manish; Chhabra, Karan R
BACKGROUND:Endoscopic sleeve gastroplasty (ESG) is increasingly utilized for treating obesity, but some patients may subsequently present for conversion to a surgical procedure. Foreign material or distorted anatomy may make conversion more challenging. The preoperative evaluation, intraoperative findings, and postoperative outcomes of converting ESG to bariatric surgery are not well described. METHODS:Bariatric surgery patients at a single center with history of ESG were identified by review of electronic medical records from 2016 to 2026. Background characteristics, preoperative imaging, endoscopic findings, intraoperative details, and outcomes were obtained by chart review. Intraoperative videos were obtained when possible. RESULTS:. Most patients (19/20, 95%) underwent preoperative esophagram, which showed a tubularized stomach in half of cases (10/19, 53%) but no radiopaque materials precluding conversion to surgery. Preoperative endoscopy (n = 5) and intraoperative endoscopy (n = 3), when performed, revealed no apparent gastroplasty. Intraoperative findings included mild adhesions around the stomach, with sutures sometimes visible, but an otherwise native stomach not requiring any changes to the staple line. Mean total weight loss was 29.1% at 1 year postoperatively. No stapler misfires occurred, and none of the postoperative complications were related to the gastric staple line. There were no gastric staple line leaks or bleeds. CONCLUSION/CONCLUSIONS:In our experience, sleeve gastrectomy and gastric bypass were both technically feasible and relatively straightforward to perform in patients with a history of ESG.
PMID: 42390801
ISSN: 1432-2218
CID: 6063332

Real-World Effectiveness of Semaglutide and Tirzepatide Compared With Bariatric Surgery

Brown, Avery; Patel, Suhani S; Kozato, Akio; Orandi, Babak J; Massie, Allan; Vu, Alexander Hien; Somoza, Eduardo; Mei, Tony; Desai, Sunita; Zhang, Donglan S; Segev, Dorry; Welcome, Akuezunkpa Ude; Ren-Fielding, Christine; Parikh, Manish; Chhabra, Karan R
OBJECTIVE:Directly compare the real-world effectiveness of semaglutide and tirzepatide to bariatric operations: sleeve gastrectomy and gastric bypass. METHODS:This study included adults with BMI ≥ 35 who received injectable semaglutide or tirzepatide (GLP-1RAs) or sleeve gastrectomy or gastric bypass (bariatric surgery) at two urban health systems from 2018 to 2024. Total weight loss (TWL) was compared up to 3 years post treatment with inverse probability weighting and mixed linear models. Intention-to-treat (any GLP-1RA) and per-protocol (1 year of continuous GLP-1RA orders) analyses were performed. RESULTS:Of 44,025 patients studied, bariatric surgery was associated with greater weight loss at 1, 2, and 3 years post treatment: semaglutide (n = 25,804) TWL (95% CI): 5.4% (5.3%-5.6%), 6.5% (6.4%-6.7%), and 7.4% (7.3%-7.6%); tirzepatide (n = 7308): 9.1% (8.9%-9.4%) and 10.8% (10.2%-11.3%); sleeve gastrectomy (n = 8728): 24.4% (24.3%-24.6%), 22.4% (22.3%-22.5%), and 22.0% (21.8%-22.1%); gastric bypass (n = 2185): 29.8% (29.7%-29.9%), 28.1% (28.0%-28.2%), and 28.4% (28.3%-28.5%). With 1 year of continuous GLP-1RA, findings were: semaglutide TWL: 7.2% (7.0%-7.4%), 8.0% (7.8%-8.2%), and 8.8% (8.6%-9.0%); tirzepatide TWL: 11.7% (11.4%-11.9%) and 11.9% (11.5%-12.3%). CONCLUSIONS:In this retrospective two-center study, bariatric surgery was associated with greater weight loss than GLP-1RAs among patients eligible for both options.
PMID: 42345739
ISSN: 1930-739x
CID: 6056092

Semaglutide vs. Bariatric Surgery: Comparing Costs and Clinical Outcomes in Patients With Diabetes and Obesity

Chhabra, Karan R; Gencerliler, Nihan; Orandi, Babak J; Wang, Vivian Hsing-Chun; Kozato, Akio; Surapaneni, Aditya; Grams, Morgan; Mukhopadhyay, Amrita; Shin, Jung-Im; Ren-Fielding, Christine; Parikh, Manish; Zhang, Donglan S
OBJECTIVE:We compared health care spending and utilization associated with semaglutide relative to bariatric surgery in patients with obesity and type 2 diabetes (T2D). METHODS:Using MarketScan insurance claims of patients with BMI ≥ 35 and T2D from 2016 to 2021, we examined associations between choice of semaglutide, sleeve gastrectomy, or gastric bypass; 3-year health care spending (out-of-pocket [OOP] and total); and clinical outcomes (ED visits, hospital admissions, and major adverse cardiovascular events [MACE]). Analyses were adjusted using generalized linear models, inverse probability weighting, and instrumental variables. RESULTS:Among 6748 patients (2797 semaglutide, 2300 sleeve gastrectomy, 1651 gastric bypass), bariatric surgery patients had higher BMI and more comorbidities. In IPTW-adjusted analysis, semaglutide was associated with the highest 3-year OOP costs ($7752 vs. $5980 [sleeve gastrectomy] vs. $6591 [gastric bypass], p < 0.001), but total spending was not statistically different across the groups. Relative to semaglutide, the gastric bypass group showed higher observed ED visits (hazard ratio relative to semaglutide [95% CI]: 1.36 [1.28-1.45]) and inpatient admissions (1.25 [1.13-1.37]) and fewer MACE (0.71 [0.59-0.88]). Sleeve gastrectomy was associated with fewer long-term admissions (0.79 [0.72-0.86]) and MACE (0.79 [0.66-0.93]). CONCLUSIONS:For patients with T2D and obesity, compared with semaglutide, bariatric surgery is associated with lower OOP spending and similar total spending at 3 years, as well as lower long-term MACE rates.
PMID: 42089543
ISSN: 1930-739x
CID: 6031282

Resting Energy Expenditure and Metabolic Adaptation Following Sleeve Gastrectomy in Hispanic Adults with Obesity

Popp, Collin J; Zhou, Boyan; Vanegas, Sally M; Reid, Migdalia; Parikh, Manish S; Ren-Fielding, Christine J; Jay, Melanie; Alemán, José O
PMID: 41912835
ISSN: 1708-0428
CID: 6021332

Efficacy and safety of direct oral anticoagulants versus enoxaparin for extended thromboprophylaxis following sleeve gastrectomy

Brown, Avery; Li, Elizabeth S; Patel, Suhani; Massie, Allan; Ihunwo, Peculiar; Schaap, Ariel; Alade, Moyosore; Ren-Fielding, Christine J; Somoza, Eduardo; Orandi, Babak J; Segev, Dorry; Parikh, Manish; Chhabra, Karan R
BACKGROUND:Extended-course enoxaparin is increasingly used after bariatric surgery to prevent venous thromboembolism (VTE), the leading cause of death after bariatric surgery. Direct oral anticoagulants are widely used for extended thromboprophylaxis outside of bariatric surgery and offered to patients in our program who cannot tolerate or obtain enoxaparin. We evaluated the safety and efficacy of apixaban 2.5 mg twice daily relative to a weight-based dose of enoxaparin 40 mg or 60 mg twice daily for 30 days after discharge following sleeve gastrectomy. METHODS:Patients aged ≥18 years who underwent laparoscopic sleeve gastrectomy from 2019 to 2024 at a single high-volume urban academic center were included. Bleeding and thrombosis outcomes within 30 days were compared between patients receiving enoxaparin 40 mg twice daily or apixaban 2.5 mg twice daily. Weighted modified Poisson analyses were used to obtain covariate balance and assess differences in bleeding and thrombosis events. RESULTS:A total of 5921 patients were included for analysis (5274 enoxaparin 40 mg twice daily, 486 enoxaparin 60 mg twice daily, and 161 apixaban 2.5 mg twice daily). The 30-day thrombosis rate was significantly lower with enoxaparin versus apixaban (.1% versus 1.9%, P < .001). The composite outcome (VTE, portomesenteric venous thrombosis, and major/minor bleeding) was also significantly lower with enoxaparin versus apixaban (1.7% versus 5.6%, P < .01). In adjusted analyses, apixaban was associated with a relative risk of 12.09 for thrombosis (95% confidence interval [CI], 5.71-31.18), 1.93 for bleeding (95% CI, 1.27-3.00), and 2.59 (95% CI, 2.06-3.27) for any adverse outcome relative to enoxaparin. CONCLUSION/CONCLUSIONS:Enoxaparin is associated with both lower thrombosis and bleeding rates compared with apixaban for extended thromboprophylaxis after sleeve gastrectomy.
PMID: 41813545
ISSN: 1878-7533
CID: 6015702

Outcomes After Bariatric Surgery in Older Adults With Obesity and End-Stage Kidney Disease

Ishaque, Tanveen; Massie, Allan B; Stewart, Darren; Li, Yiting; Chen, Yusi; Menon, Gayathri; Ghildayal, Nidhi; Montgomery, John R; Seckin, Timur; Chhabra, Karan R; Jenkins, Megan E; Ren-Fielding, Christine J; McAdams-DeMarco, Mara A; Segev, Dorry L; Orandi, Babak J
OBJECTIVE:Given frailty and comorbidities that occur with both aging and end-stage kidney disease (ESKD), it is unclear if older patients with ESKD derive the improved survival and kidney transplant (KT) access associated with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). METHODS:Using 2006-2021 USRDS data, we identified 876 patients with RYGB and 1508 patients with SG and compared 5-year mortality by age-group (18-29/30-39/40-49/50-59/60-69/≥ 70 years) to nonsurgical matched controls using 1:3 Mahalanobis distance matching, Kaplan-Meier, and Cox regression. We also compared age-stratified KT incidence between waitlisted patients and controls. RESULTS:) for patients with SG versus controls. CONCLUSIONS:RYGB in older patients with ESKD is associated with increased mortality and lower KT likelihood, whereas SG is associated with decreased mortality and higher KT likelihood compared to nonsurgical matched controls. Choice of bariatric surgery type may play a role in improving survival for older patients with ESKD.
PMCID:12643172
PMID: 41266080
ISSN: 1432-2323
CID: 5976062