GLP-1 analogues and prostate cancer incidence: A systematic review and meta-analysis.

Abstract

374 Background: Preliminary evidence from preclinical and observational data suggests that GLP-1 receptor agonists (GLP-1RAs) may reduce prostate cancer (PCa) incidence. We aimed to assess the effects of GLP-1RAs on PCa risk. Methods: Embase, Medline, Web of Science, and Cochrane databases were searched from inception to identify phase III randomized controlled trials (RCTs) comparing a GLP-1 RA with placebo/non-GLP-1 RA regimens. The primary outcome was incidence of PCa. A Mantel-Haenszel random-effect meta-analysis was carried out to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for the occurrence of PCa among male participants. Results: Of the 27,103 abstracts identified, 56 trials including 59,334 male participants were included. Eligibility included type 2 diabetes mellitus in 48 studies, obesity in 7 studies, and heart failure in 1 study. The GLP-1 RA’s studied included liraglutide (18), semaglutide (13), dulaglutide (6), albiglutide (6), lixisenatide (5), exenatide (4), and others (5). One study included both liraglutide and semaglutide as interventions. Follow-up durations ranged from 12 weeks to 260 weeks (5 years), with a mean of 72.5 weeks (standard deviation = 50.85). The pooled incidence of PCa was 0.55% (150 of 27,126) for the control group and 0.46% (148 of 32,208) for the GLP-1 intervention group. The pooled RR of PCa incidence with all GLP-1 RAs compared to controls was 0.86 (95% CI: 0.69-1.06, p=0.16). Conclusions: There were proportionally fewer incident PCa cases among GLP-1 RA recipients as compared with control. However, this did not achieve statistical significance. Trials were limited in duration and by the lack of pre-specification of this outcome. Further research is needed to evaluate whether GLP-1 RAs have activity against established PCa.