medwireNews: The reduced prostate cancer risk seen in men with diabetes may be partly explained by detection bias due to a lower biopsy rate following an elevated prostate-specific antigen (PSA) test result, population-based study data show.
Kerri Beckmann (King’s College London, UK) and co-investigators say their “findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer.”
The study included men identified from the Stockholm PSA and Biopsy Register between 2006 and 2015 who received their first prescription for metformin (n=4583), a sulfonylurea (n=1104), insulin (n=978), or any antidiabetic medication (n=4424) between two consecutive PSA tests that occurred within 2 years either side of the first prescription, with 30 days or more of exposure before the second test. These men were each matched to five controls who were not exposed to antidiabetic medication but underwent PSA testing during the same period.
The researchers report in JAMA Network Open that, prior to antidiabetic treatment initiation, men in the exposure groups had significantly lower baseline PSA levels than those in the unexposed groups (mean 1.2 vs 1.6 ng/mL).
However, after accounting for this disparity, the team found that there was no significant difference in PSA level in the 2 years after treatment initiation between the men who were and were not exposed to antidiabetic medication overall as well as each specific class.
Beckmann and team also observed that men receiving metformin or a sulfonylurea were a significant 7% and 6% more likely, respectively, to undergo PSA testing than those not taking any antidiabetic medication. Conversely, men receiving insulin were a significant 21% less likely to have a PSA test, while those receiving any diabetic medication were a significant 7% less likely.
In addition, the likelihood of undergoing a biopsy within 12 months of an elevated PSA result (≥3.0 ng/mL) was a significant 13%, 13%, and 17% lower among men receiving any antidiabetic drug, metformin, and insulin, respectively, and a nonsignificant 12% lower for those receiving a sulfonylurea, relative to men not exposed to these medications.
However, the researchers note that they “cannot determine whether this association was due to decreased referral rates or lower compliance with biopsy recommendations.”
Once a biopsy was carried out, the prostate cancer detection rate did not differ between the exposed and unexposed men for any of the antidiabetic medications studied, regardless of the PSA level that triggered the biopsy.
This suggests that “use of diabetes medications is not associated with prostate cancer detection at biopsy,” Beckmann et al remark.
They add: “If lower PSA levels were masking the presence of prostate cancer, an increase in prostate cancer detection might be expected.”
In an accompanying comment, Kyla Velaer and John Leppert, both from Stanford University Medical School in California, USA, say that the study “questions the role of diabetes medications in the chemoprevention of prostate cancer.”
They add: “The presence of lower PSA values before exposure to diabetes medications suggests that PSA values are associated with the presence of diabetes or other comorbidities like obesity and metabolic syndrome that are commonly found in men with diabetes.”
Based on the findings, the commentators conclude that “[c]linicians can continue to use similar PSA thresholds when considering prostate biopsy in men with or without exposure to diabetes medications.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
JAMA Netw Open 2019; 2: e1914689
JAMA Netw Open 2019; 2: e1914644