Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer

Abstract

Objective: Diabetic men have lowered overall prostate cancer (PCa) risk, while their risk of high-grade disease may be elevated. The antidiabetic drug metformin may reduce the risk. This study evaluated PCa incidence among users of metformin and other antidiabetic drugs in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

Methods: The study population (78,615 men) was linked to the national prescription database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PCa were estimated using Cox regression, with medication use as a time-dependent variable. The effect of diabetes was estimated by comparing antidiabetic drug users to non-users, while drug-specific effects were evaluated within antidiabetic drug users. Analyses were performed in both study arms of FinRSPC.

Results: Compared to non-users, men using antidiabetic drugs had lowered overall PCa risk (HR 0.85, 95% CI 0.79–0.92), and this association was not affected by PCa screening. However, the risk of metastatic PCa was increased (HR 1.44, 95% CI 1.09–1.91). Among antidiabetic drug users, metformin decreased overall PCa risk (HR 0.81, 95% CI 0.69–0.95) in a dose-dependent manner. When stratified by FinRSPC study arm, the risk reduction was observed only in the screening arm. Sulphonylureas increased the risk of metastatic PCa (HR 2.04, 95% CI 1.11–3.77). Use of thiazoledenediones or insulin was not associated with PCa risk.

Conclusion: Among antidiabetic drug users, metformin lowered the overall PCa risk, while the risk of metastatic disease was elevated in sulphonylurea users. As sulphonylureas stimulate insulin secretion, the results suggest that hyperinsulinemia may be a risk factor for PCa.

Keywords:

• Cohort
• diabetes mellitus
• metformin
• prostate cancer
• risk

Disclosure statement

T. J. Murtola has received lecture fees from Janssen-Cilag, Abbvie and MSD, and is a paid consultant for Astellas and Janssen-Cilag. K. Taari has received a lecture fee from GSK, has a paid consultancy with Abbvie, is an employee of Medivation, and was a participant in an international meeting with sponsors Astellas and Orion. T. L. J. Tammela is a paid consultant for Astellas, GSK, Pfizer, Orion Pharma and Amgen. A. Auvinen has received a lecture fee from MSD and is a paid consultant with Epid Research. A. Haring and K. Talala have declared no conflicts of interest.

Additional information

Funding

This work was supported by PhD researcher funding from the University of Tampere School of Medicine to A. Haring and by research grants from the Finnish Cultural Association and the Pirkanmaa Hospital District to T.J. Murtola.