Incretin-based Drugs and the Incidence of Prostate Cancer Among Patients with Type 2 Diabetes

Background: There is some evidence from laboratory studies and randomized controlled trials that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors may have chemopreventive effects on prostate cells and decrease the risk of prostate cancer. However, real-world evidence for this possible effect is lacking.

Objectives: To determine whether the use of GLP-1 RAs and DPP-4 inhibitors, separately, is associated with a decreased risk of prostate cancer among patients with type 2 diabetes.

Methods: We assembled two new-user, active comparator cohorts of patients with type 2 diabetes using the United Kingdom Clinical Practice Research Datalink (2007 to 2019). The first cohort included 5063 initiators of GLP-1 RAs and 112,955 initiators of sulfonylureas, while the second cohort included 53,529 initiators of DPP-4 inhibitors and 114,417 initiators of sulfonylureas. Patients were considered exposed from the date of the first prescription until the end of the follow-up period, regardless of treatment discontinuation or crossover to one of the other study drugs. Cox proportional hazards models were fitted to estimate adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of incident prostate cancer, separately for GLP-1 RAs and DPP-4 inhibitors. The models were weighted using propensity score fine stratification.

Results: In the first cohort, GLP-1 RAs were associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates: 156.4 vs. 232.0 per 100,000 person-years, respectively; HR: 0.65, 95% CI: 0.43-0.99) after a median follow-up of 5.0 years. In the second cohort, DPP-4 inhibitors were also associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates: 316.2 vs. 350.5 events per 100,000 person-years, respectively; HR: 0.90, CI: 0.81-1.00), after a median follow-up of 4.2 years.

Conclusions: The results of this large population-based cohort study indicate that the use of GLP-1 RAs and DPP-4 inhibitors, separately, may decrease the risk of prostate cancer when compared with the use of sulfonylureas among individuals with type 2 diabetes.