medwireNews: Prostate-specific antigen (PSA) levels are not significantly affected by use of diabetes medication, say researchers who also found the likelihood of prostate cancer detection at biopsy was comparable between men with and without diabetes.
“This study’s 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”, say Kerri Beckmann, from King’s College London in the UK, and co-authors in JAMA Network Open.
“They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes”, they report.
The team collated data from the population-based Stockholm PSA and Biopsy Register of 564,666 men aged 40 to 79 years who were free from prostate cancer and living in Stockholm County in Sweden between 2006 and 2015.
Of this cohort, 4583 men used metformin, 1104 used a sulphonylurea and 978 men used insulin, and these were each matched by age to five men without exposure to these diabetes medications, the researchers explain.
Analysis showed that men using diabetes medications had lower median PSA levels before beginning treatment than their unexposed counterparts (1.2 vs 1.6 ng/mL), and this was true for each of the diabetes drug classes regardless of patient age.
However, post-treatment PSA levels did not significantly differ between men who were using diabetes medications and those who never used such agents after adjusting for premedication PSA, education, civil status, comorbidity, family history of prostate cancer and other known confounding factors.
Multivariate analysis indicated that more frequent PSA testing was associated with marriage, greater education and a familial history of prostate cancer, as well as use of metformin or sulphonylureas compared with nonusers. By contrast, men using insulin had a lower frequency of PSA tests than those who were not, and overall any use of any diabetic medication was associated with a significantly lower rate of PSA testing (rate ratio=0.93)
Moreover, men receiving metformin or insulin were significantly less likely than nonusers to undergo biopsy after an elevated PSA test, with odds ratios (OR) of 0.87 and 0.83, respectively. The rate of biopsy did not differ with or without sulphonylurea use and overall, any diabetic medication use was associated with a significantly lower rate of prostate biopsy compared with no use (OR=0.77 for biopsy after PSA of 4 ng/mL or higher).
And regardless of whether prostate biopsy was triggered by a PSA of 3.0 ng/mL or a higher threshold, the likelihood of prostate cancer detection at biopsy did not differ between men using any of the three diabetes medications and nonusers, report Kerri Beckmann and co-investigators.
The authors of an invited commentary say that “these data suggest that diabetes medications are not associated with the modification of PSA values or the likelihood of being diagnosed with prostate cancer.”
“Clinicians can continue to use similar PSA thresholds when considering prostate biopsy in men with or without exposure to diabetes medications”, recommend Kyla Velaer and John Leppert, both from Stanford University Medical School in California, USA.
“The prior reports suggesting a lower risk of prostate cancer in men receiving diabetes medications can be partially explained by detection bias rather than a protective effect of diabetes medications.”
The commentators conclude: “While the volume and grade of prostate cancer was not included in this report, future studies will help determine whether diabetes medications may be associated with the diagnosis of clinically significant (high-grade or high-volume) prostate cancer.”
- Beckmann K, Crawley D, Nordström T, et al. Association between antidiabetic medications and prostate-specific antigen levels and biopsy results. JAMA Netw Open 2019; 2: e1914689. doi:10.1001/jamanetworkopen.2019.14689
- Velaer KN, Leppert JT. Diabetes medications, prostate-specific antigen values, and the chemoprevention of prostate cancer. JAMA Netw Open 2019; 2: e1914644. doi:10.1001/jamanetworkopen.2019.14644
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