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

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.