February 12, 2020
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Statins alone, with metformin linked to reduced mortality among men with high-risk prostate cancer

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Grace Lu-Yao, PhD
Grace Lu-Yao

Use of statins as monotherapy or in combination with metformin appeared associated with lower mortality among men with high-risk prostate cancer, according to results of a retrospective study published in Cancer Medicine.

“Both metformin and statins have been associated with longer life [among men with] prostate cancer, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately,” Grace Lu-Yao, PhD, associate director of population science at Sidney Kimmel Cancer Center at Jefferson Health, said in a press release.

About 15% of men diagnosed with prostate cancer have high-risk disease, meaning they have a significant chance of developing systemic or local recurrence and a higher risk for death due to the disease. Although preclinical studies indicated the diabetes drug metformin and cholesterol-lowering statins might delay prostate cancer metastases, the individual and joint effects of their use among men with high-risk disease had not been quantified.

To achieve this, Lu-Yao and colleagues used the SEER-Medicare linked database to retrospectively analyze 12,700 men (median age at diagnosis, 74 years; range, 70-80) diagnosed with high-risk prostate cancer between 2008 and 2011 who survived for at least 6 months. They defined high-risk disease as T category of T2c or greater, PSA of 20 or greater, or Gleason score of 8 or higher.

Among these men, 4,568 did not take metformin or statins, 435 took metformin alone, 5,786 took statins alone and 1,911 took metformin in combination with statins.

Median follow-up was 42 months (range, 26.4-57.6), during which 2,182 men (17.2%) died of any cause and 1,078 (8.5%) died of prostate cancer.

Results showed median survival of 3.1 years with metformin monotherapy, 3.6 years with statin monotherapy and 3.9 years with metformin in combination with metformin. Men who used neither drug had median survival of 3.1 years.

Using Cox proportional hazards models, researchers observed significant associations between use of metformin plus statins (HR = 0.75; 95% CI, 0.67-0.83), as well as statin monotherapy (HR = 0.89; 95% CI, 0.83-0.96), and lower all-cause mortality.

Additionally, metformin plus statin use appeared associated with a 36% reduction in risk for prostate cancer mortality (HR = 0.64; 95% CI, 0.51-0.81). Statin monotherapy appeared associated with a 20% risk reduction (HR = 0.8; 95% CI, 0.69-0.92).

Metformin monotherapy demonstrated no significant association with all-cause or prostate cancer mortality.

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The effects of statin monotherapy and statins with metformin appeared more pronounced among men who initiated use after prostate cancer diagnosis.

Among these post-diagnostic users, statin monotherapy resulted in a 27% reduction in all-cause mortality (HR = 0.73; 95% CI, 0.64-0.84) and a 42% reduction in prostate cancer mortality (HR = 0.58; 0.43-0.78) compared with men who did not receive statins or metformin.

Metformin in combination with statins, meanwhile, appeared associated with a 32% reduction in all-cause mortality (HR = 0.68; 95% CI, 0.57-0.8) and a 54% reduction in prostate cancer mortality (HR = 0.46; 95% CI, 0.3-0.69) among post-diagnostic users.

Subanalyses showed that among the statins used, only lovastatin did not appear significantly associated with a reduction in prostate cancer mortality. Further, results showed no statistically significant difference in the effects of lipophilic vs. hydrophilic and high- vs. low-potency statins.

“Our study showed that the effects were more pronounced in patients taking statins after the diagnosis of prostate cancer, [including] a 54% reduction in prostate cancer mortality among patients with high-risk prostate cancer,” Lu-Yao said in the press release. “This magnitude of reduction is comparable to the results of men treated with androgen signaling inhibitors. Statins are relatively inexpensive with good safety records. Further studies to understand the mechanisms of the observed association and its potential clinical utility are warranted.” – by John DeRosier

Disclosures: The authors report no relevant financial disclosures.