Statins and Metformin Could Lower Risk of Death in Prostate Cancer Patients
FEBRUARY 11, 2020
Grace Lu-Yao, PhD, MPH
Preliminary research from Thomas Jefferson University involving more than 12,000 patients indicates use of statins in combination with metformin could lead to a 32% reduction in all-cause mortality and a 54% reduction in prostate cancer death in patients with high-risk prostate cancer.
"Both metformin and statins have been associated with longer life in prostate cancer patients, yet because they are commonly prescribed together, no study we know of has looked at these two medications separately," said lead investigator Grace Lu-Yao, PhD, MPH, associate director of Population Science at the Sidney Kimmel Cancer Center—Jefferson Health, in a statement.
With data from pre-clinical studies indicating metformin and statins may delay prostate cancer metastases, investigators aimed to conduct what they claim is the first human study to masses the individual and joint effects of statin and metformin use in patients with high-risk prostate cancer. To do so, Lu-Yao and a team of colleagues conducted a retrospective cohort study of patient data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database.
Primary outcomes of the current analysis include all-cause and prostate cancer mortality, which were evaluated using Cox proportional hazard model that used propensity matching to adjust for imbalances in covariates across groups. Interventions of interest included exposure to metformin and statins, which was identified using Part D prescription drug event files.
Specific statins examined in the analysis included pravastatin, rosuvastatin, atorvastatin, fluvastatin, lovastatin, and simvastatin.
From the 123,578 prostate cancer patients included in SEER, 12,700 met the inclusion criteria for the current analysis. For inclusion in the study, participants were required to have survived for 6 months or more after diagnosis and have been diagnosed with high-risk prostate cancer between 2008 and 2011. high-risk prostate cancer was defined as a T category of T2c or higher, prostate specific antigen level of 20 or higher, a Gleason score of 8 or more, or equivalent to overall cancer stage IIB or greater.
Among the 12,700 who met inclusion criteria, the median age at diagnosis was 74 years and the median follow-up time was 42 months. Of the 12,700 participants, 435 used only metformin, 5786 used only statins, 1911 used both, and 4568 did not use either.
During the follow-up, 2182 participants (17.2%) died from any cause and 1078 (8.5%) died from prostate cancer. When examining survival time by group, median survival was higher with metformin plus statin at 3.9 years and statin alone at 3.6 years compared to 3.1 years for participants who did not use either therapy—median survival among metformin only patients was also 3.1.
Results of the investigators’ Cox models indicated metformin plus statin (HR 0.75; 95% CI, 0.67‐0.83) and statin alone (HR 0.89; 95% CI, 0.83‐0.96) were significantly associated with lower all-cause mortality after adjustment for potential covariates. When examining prostate cancer mortality, metformin plus statin was associated with a 36% reduction in risk (HR 95% CI, 0.51‐0.81) while statin alone was associated with a 20% reduction (HR 0.80; 95% CI, 0.69‐0.92).
Lu-Yao and colleagues pointed out that metformin alone was rare and results indicated there was no significant association with all-cause (HR 0.89; 95% CI, 0.75‐1.05) or prostate cancer mortality (HR 0.75; 95% CI, 0.53‐1.05). Additionally, the effects appeared to be more pronounced in post-diagnostic users—with use of metformin and statins associated with a 32% reduction in all-cause mortality (HR 0.68; 95% CI, 0.57‐0.80) and a 54% reduction in prostate cancer mortality (HR 0.46; 95% CI, 0.30‐0.69) in this subgroup.
This study, “Individual and joint effects of metformin and statins on mortality among patients with high‐risk prostate cancer,” was published online in Cancer Medicine.