Adverse Event Comparison between Glucagon-like Peptide-1 Receptor Agonists and Other Anti-Obesity Medications Following Bariatric Surgery

Introduction The safety of Glucagon-like Peptide 1 Receptor Agonists (GLP1RAs) following bariatric surgery remains largely unknown. This study aims to compare the incidence of adverse events (AEs) with GLP1RAs and other anti-obesity medications (AOMs) after bariatric surgery. Methods This single-center retrospective cohort included patients (ages 16-65) if they met the following criteria: underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Subjects were categorized as users of ‘FDA-approved’ or ‘off label’ AOMs or GLP1RAs AOMs if documented as receiving the medication on the cohort entry date or after. Non-GLP1RA AOMs were Phentermine, Orlistat, Topiramate, Canagliflozin, Dapagliflozin, Empagliflozin, Naltrexone, Bupropion/Naltrexone, and Phentermine/Topiramate. GLP1RAs AOMs included: Semaglutide, Dulaglutide, Exenatide, Liraglutide. Primary outcome was AEs incidence. Logistic regression was used to determine the association of AOM exposure with AEs. Results We identified 599 patients meeting inclusion criteria (83% female, median 47.8 years old (IQR 40.9 – 55.4). Median surgery to AOM duration was 30 months (IQR 0 – 62). GLP1RAs were not associated with higher odds of AEs (adjusted Odds Ratio, (aOR) 1.1, [95% CI 0.5 – 2.6] and 1.1 [95% CI 0.6 – 2.3] for GLP1RA versus FDA-approved and ‘Off-Label’ AOMs, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01. [95% CI 0.0 – 0.01], p<0.001). Conclusion GLP1RAs were not associated with an increased risk of AEs compared to non-GLP1RA AOMs in patients who previously underwent bariatric surgery. Prospective studies are needed to identify the optimal timeframe for initiation of GLP1RA. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by the resources and funding provided by the NIH NCATS award 5UL1TR002243 03 and UL1TR000445 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has been approved by the Vanderbilt University Medical Center Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors