Therapeutic-dose semaglutide and tirzepatide cut colorectal and pancreatic cancer risk in obese, non-diabetic adults.

Obesity is a major risk factor for several cancers, including colorectal cancer (CRC), pancreatic cancer, and hepatocellular carcinoma (HCC). While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown promise in reducing cancer risk, most evidence comes from diabetic populations. A critical knowledge gap exists regarding their impact on obesity-associated cancer risk in non-diabetic individuals, especially when compared to established interventions like bariatric surgery or other weight-loss medications. Understanding this distinction is vital for comprehensive patient counseling and treatment strategies.

This retrospective cohort study utilized the TriNetX Research network to analyze data from non-diabetic adults with obesity. Researchers compared three groups: those receiving semaglutide or tirzepatide, those undergoing bariatric surgery, and those using other weight-loss medications (orlistat, phentermine/topiramate, or naltrexone/bupropion). Patients were stratified by GLP-1 RA dose (any vs. therapeutic) and meticulously propensity-score matched to minimize confounding. Cancer incidence for CRC, pancreatic cancer, and HCC was assessed using Kaplan-Meier analysis and Cox proportional hazards models as primary endpoints.

The study identified a massive cohort, including 662,013 GLP-1 RA users, 272,343 bariatric surgery patients, and 158,446 users of other weight-loss medications. Therapeutic-dose GLP-1 RA use demonstrated significant benefits compared to bariatric surgery, showing a lower incidence of CRC (hazard ratio [HR], 0.72; P =.038) and pancreatic cancer (HR, 0.63; P =.041). No significant difference was observed for HCC risk in this comparison. When therapeutic-dose GLP-1 RAs were compared to other weight-loss medications, a lower CRC risk was also observed (HR, 0.68; P =.008), without significant differences in pancreatic or liver cancer incidence. Importantly, the use of any GLP-1 RA dose (not specifically therapeutic) was not associated with significant differences in cancer risk across comparisons. This highlights the importance of adequate dosing.

Therapeutic-dose GLP-1 RAs were associated with a 28% lower incidence of colorectal cancer and a 37% lower incidence of pancreatic cancer compared to bariatric surgery.