(A-050) Association of Glucagon-Like Peptide 1 Receptor Agonists with Cancer Risk in Older Adults with Type 2 Diabetes: A Target Trial Emulation Study

Background: The dramatically increasing use of glucagon-like peptide 1 receptor agonists (GLP-1RAs) for glycemic control and weight management necessitates a comprehensive understanding of their potential impact on cancer risk. However, real-world evidence on the association between glucagon-like peptide 1 receptor agonists (GLP-1RAs) and cancer remains limited and mixed.

Objectives: To compare risk of obesity-associated cancers in older patients with type 2 diabetes (T2D) newly prescribed GLP-1RA versus sodium-glucose cotransporter-2 inhibitors (SGLT2i) or dipeptidyl peptidase-4 inhibitors (DPP4i).

Methods: We performed a target trial emulation study using U.S. Medicare national administrative claims data from 2013 to 2020. The study included patients aged ≥66 years with T2D and no prior cancer diagnosis, who initiated treatment with GLP-1RAs, SGLT2is, or DPP4is. We examined the incidence of nine obesity-related cancers: thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancers. Propensity-score matching was applied to minimize confounding, and hazard ratios (HRs) and cumulative incidences were estimated using Cox proportional hazard models and Kaplan-Meier analyses.

Results: After 1:1 PS matching, the cohort consisted of 21,362 matched pairs of patients for GLP-1RA vs. SGLT2i comparison, and 20,962 matched pairs for GLP-1RA vs. DPP4i comparison. In the GLP-1RA vs. SGLT2i comparison, the incidence rate (IR) of the overall nine cancers was 31.33 per 1,000 person-years for GLP-1RA users and 30.25 for SGLT2i users. GLP-1RA users had similar overall cancer risk with SGLT2i users (HR, 1.03 [95% CI, 0.95-1.12]) but were associated with an increased kidney cancer risk (HR, 1.43 [1.06 to 1.92]). For GLP-1RA vs. DPP4i, the IR of the overall nine cancers was 31.43 per 1,000 person-years for GLP-1RA users versus 32.72 for DPP4i users. While overall cancer risk was not significant different (HR, 0.96 [0.89-1.04]), GLP-1RA use was associated with significantly elevated endometrial cancer risk (HR, 1.55 [1.01-2.37]).

Conclusions: While GLP-1RAs were not associated with a significant increase in the overall risk of obesity-associated cancers compared to SGLT2is or DPP4is, they were associated with increased risk of specific cancers—such as kidney and endometrial cancer—when compared to SGLT2is and DPP4is, respectively. These findings underscore the need for ongoing monitoring and further long-term studies to fully understand the impact of GLP-1RAs on cancer risk in this population.