Comparative risk of obesity-related cancer with glucagon-like protein-1 receptor agonists vs. bariatric surgery in patients with BMI ≥ 35.

10508 Background: Bariatric surgery is suggested to reduce the risk of obesity-related cancers, prompting us to explore whether glucagon-like peptide-1 receptor agonist (GLP-1 RA) offers a similar association. Methods: We queried TriNetX, a global healthcare database to identify patients with BMI of ≥ 35. Three pair-wise propensity score-matched (PSM) comparisons were created: 1) GLP-1 RA vs. Bariatric Surgery, 2) GLP-1 RA vs. No Intervention, 3) Bariatric Surgery vs. No Intervention. Cohorts were exclusive and no intervention was defined as an ambulatory visit. Patients required a minimum of 1 year of continuous GLP-1 RA therapy or follow-up, extended to 3 and 5 years in sensitivity analyses. Exclusions included a history of cancer or in situ neoplasms, as well as factors that significantly impact cancer risk and/or mortality including alcohol use disorder, organ transplantation, HIV, decompensated cirrhosis, peptic ulcer disease, dialysis dependency, left ventricular ejection fraction ≤ 20%, or other weight loss medication exposure. PSM utilized obesity therapy indications, Elixhauser and Charlson Comorbidity indices, prior follow-up, and demographics. Follow-up extended to 15 years, assessing 13 obesity-related cancers after intervention using Kaplan Meier (KM) and Cox-proportional Hazards Models (HR). Secondary outcomes included the risk of all-cause mortality and precancerous lesions. Results: After PSM, we identified 20,009, 3,229, and 11,104 patients in Comparison 1, 2, and 3, respectively. For Comparison 1, at 15 years, 273 (KM event rate 8.75%) patients on GLP-1 RA therapy and 397 (6.58%) with bariatric surgery developed an obesity-associated cancer, respectively (HR 0.99; 95% CI 0.87 - 1.13). Patients who received GLP-1 RA (HR 0.61; 95% CI 0.46 - 0.81) and bariatric surgery (HR 0.78; 95% CI 0.67 - 0.91) had a reduced risk of obesity-related cancer compared to no intervention. Among 20,009 patients, 40 (0.353%) and 61 (0.876%) of patients developed thyroid cancer in the GLP-1 RA and bariatric surgery groups, respectively (HR: 0.837; CI: 0.558 - 1.254). Patients lost significantly more weight after bariatric surgery as compared to GLP-1 RA at 1-2 years (BMI change -5.31 ± 6.05 vs. -1.57 ± 5.12 kg/m 2 ; p < 0.0001). GLP-1 RA initiation was associated with lower all-cause mortality compared to control (HR 0.5; 95% CI 0.40 - 0.62) and bariatric surgery (HR 0.859; 95% CI 0.77 - 0.96). Neither GLP-1 RA nor bariatric surgery was associated with precancerous lesions compared to control. Sensitivity analyses supported the above outcomes. Conclusions: GLP-1 RA was associated with a lower risk of obesity-related cancer comparable to bariatric surgery in patients with BMI ≥ 35. GLP-1 RA has superior all-cause mortality benefits despite inferior weight loss compared to bariatric surgery.