Cancer risk of glucagon-like peptide-1 receptor agonists for obesity: comparison with bariatric surgery and other weight-loss drugs.

“Cancer risk of glucagon-like peptide-1 receptor agonists for obesity: comparison with bariatric surgery and other weight-loss drugs. Bitar ER(1), Besir K(2), Cummins KC(1), Sears O(1), El Moheb M(1), McKee K(1), Ruff SM(1), van der Windt DJ(3), Tsung A(4). Author information: (1)Department of Surgery, University of Virginia, Charlottesville, VA, United States. (2)Digestive Disease Research Center, Medical University of South Carolina, Charleston, SC, United States. (3)Department of Surgery, Medical University of South Carolina, Charleston, SC, United States. (4)Department of Surgery, University of Virginia, Charlottesville, VA, United States. Electronic address: allantsung@virginia.edu. BACKGROUND: Obesity is associated with an increased risk of several cancers, including colorectal cancer (CRC), pancreatic cancer, and hepatocellular carcinoma (HCC). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been linked to a lower risk of certain obesity-associated cancers, but most studies have focused on patients with diabetes. Their impact on nondiabetic patients using GLP-1 RAs for weight loss remains unclear. METHODS: Using the TriNetX Research network, we conducted a retrospective cohort study of nondiabetic adults with obesity who received semaglutide or tirzepatide, underwent bariatric surgery, or used other weight-loss medications (orlistat, phentermine/topiramate, or naltrexone/bupropion). Patients were stratified by GLP-1 RA dose (any vs therapeutic) and propensity-score matched. Cancer incidence was assessed using Kaplan-Meier analysis and Cox proportional hazards models. RESULTS: We identified 662,013 GLP-1 RA users, 272,343 bariatric surgery patients, and 158,446 users of other weight-loss medications. Compared with bariatric surgery, therapeutic-dose GLP-1 RA use was associated with a lower incidence of CRC (hazard ratio [HR], 0.72; P =.038) and pancreatic cancer (HR, 0.63; P =.041), but not HCC. Compared with other weight-loss medications, therapeutic-dose GLP-1 RAs were associated with a lower CRC risk (HR, 0.68; P =.008), without significant differences in pancreatic or liver cancer. The use of any dose was not associated with significant differences. CONCLUSION: Therapeutic-dose GLP-1 RA use was associated with a lower incidence of CRC and pancreatic cancer compared with bariatric surgery and with a lower incidence of CRC compared with other weight-loss medications. These findings suggest that GLP-1 RA use is not associated with an increased cancer risk and raise the possibility that therapeutic-dose treatment may be associated with a lower cancer incidence. Copyright © 2026 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved. Conflict of interest statement: Declaration of competing interests The authors declare no competing interests.”