PEN-HUA SU2026-10-162026-10-162026-10-01Pure ID: 15446442Pure UUID: c6727880-e2cd-446d-bfde-1964460cae5410.1097/MJT.0000000000002132https://www.scopus.com/pages/publications/105037143772https://scholars.csmu.edu.tw/handle/123456789/26491Background: – Laboratory changes after antiobesity drugs in routine care are not well-described. Study Question: – In adults with obesity and no diabetes, how do 2-year laboratory trends and major clinical outcomes compare after starting semaglutide versus naltrexone-bupropion or phentermine-topiramate? Study Design: – Retrospective cohort study in the TriNetX US Collaborative Network (2021–2025). New users were propensity-score matched 1:1 and followed for up to 24 months in an intention-to-treat framework. A prespecified 3-month landmark analysis and a global network replication were performed. Measures and Outcomes: – Lipids, HbA1c, ALT, AST, lipase, creatinine, and estimated glomerular filtration rate were assessed at baseline and at 6, 12, and 24 months. Outcomes were all-cause mortality, major adverse kidney events (MAKEs), major adverse liver outcomes, and acute pancreatitis. Cox models estimated hazard ratios (HRs); 24-month absolute risk differences (ARDs) were derived from Kaplan–Meier estimates. Results: – Matching yielded 11, 484 semaglutide–naltrexone–bupropion pairs and 16, 316 semaglutide–phentermine–topiramate pairs. Compared with each comparator, semaglutide users had lower total cholesterol and LDL-C across follow-up; triglycerides were lower versus naltrexone–bupropion. HDL-C was higher with phentermine–topiramate at 12–24 months. HbA1c was lower with semaglutide versus naltrexone–bupropion at 12 and 24 months and slightly higher versus phentermine–topiramate. Between-group differences in creatinine and estimated glomerular filtration rate were limited. Semaglutide use was associated with lower hazards of mortality (vs. naltrexone–bupropion: HR 0.51; ARD −0.4%; vs. phentermine–topiramate: HR 0.62; ARD −0.2%) and MAKE (vs. naltrexone–bupropion: HR 0.47; ARD −0.5%; vs. phentermine–topiramate: HR 0.48; ARD −0.4%). Major adverse liver outcome and pancreatitis estimates were near the null, and landmark results were similar. Conclusions: – Over 2 years in routine care, semaglutide use was associated with lower atherogenic lipid levels and lower hazards of death and MAKEs than naltrexone–bupropion or phentermine–topiramate, while kidney laboratory differences were limited.enjournal article