(A-098) Glucagon-Like Peptide-1 Receptor Agonists for the Prevention of Genitourinary Cancers: A Systematic Review of Observational Studies

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are drugs used to treat type 2 diabetes and obesity. Emerging evidence suggests potential anti-tumour properties on genitourinary cancers. However, no systematic reviews have synthesized evidence from observational studies investigating this potential link.

Objectives: To systematically search and describe observational studies investigating the association between GLP-1 RAs and the incidence of genitourinary cancers.

Methods: We systematically searched MEDLINE, Embase, and Web of Science from January 1, 2005, through October 31, 2024. Eligible studies included English-language observational studies assessing genitourinary cancer risks in GLP-1 RA users with relevant comparators, regardless of indication. The genitourinary cancers considered were bladder, kidney, prostate, and urothelial.

Results: We identified 6548 articles from the initial database search, of which six observational studies met the inclusion criteria, all involving patients with type 2 diabetes. Some studies compared GLP-1 RAs with multiple antihyperglycemic drug classes, such as metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, sulfonylureas, and insulin. Two studies focused on bladder cancer, one on kidney cancer, three on prostate cancer, and one on urothelial cancer. The reported hazard ratios (HRs) varied widely: for bladder cancer, HRs ranged from 0.85-1.10 (vs. metformin and SGLT-2 inhibitors, respectively); for kidney cancer, HRs ranged from 0.76-1.54 (vs. insulin and metformin, respectively); for prostate cancer, HRs ranged from 0.91-1.05 (vs. sulfonylureas); and for urothelial cancer: HR was 1.05 (vs. sulfonylureas). Variability in findings likely reflects heterogeneity in study designs, the choice of the comparators, and methodological limitations, such as residual confounding and time-related biases.

Conclusions: This review highlights inconsistent findings on the link between GLP-1 RAs and genitourinary cancers. While emerging evidence suggests potential anti-tumor effects of GLP-1 RAs, additional well-designed observational studies are needed to address methodological challenges.