Target trial emulation of the association of GLP-1 receptor agonist use and cancer risk in obese nondiabetic adults

Incidences of obesity and obesity-associated cancers (OACs) are increasing worldwide. Recent data show dat glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with decreasing cancer incidence in diabetic and obese patients. There have been no studies exclusively investigating the association of OAC risks and GLP-1RA use in obese, nondiabetic patients. An emulated trial using TriNetX (database of 113 million US patients) evaluated the association between GLP-1RA use and risk of 13 OACs among obese, nondiabetic adults form December 2014 to June 2025. The cohort included 229 467 patients, with 37.7% receiving GLP-1RAs and 63.2% receiving diet or exercise consultation. After propensity score matching, the study cohort included 80 899 GLP-1RA users and 80 899 patients on diet or exercise consultation. Mean age of patients was 47.2 ± 14.8 years. With a median follow-up of 2 years (IQR 1-2) the propensity score matching analysis showed a significantly lower incidence of any OACs among GLP-1RA users (HR 0.59; 95% CI 0.53-0.67). Secondary analyses showed that in all subgroups, except for Black race, GLP-1RA use was associated with a lower cumulative incidence of OACs. IPTW analysis confirmed the findings. The authors conclude that GLP-1RA us was associated with a signifantly lower short-term incidence of OACs among obese, nondiabetic patients.