The Use of Metformin in Patients with Prostate Cancer and the Risk of Death

Abstract

Background: Given the conflicting results from observational studies, we assessed whether the use of metformin after a prostate cancer diagnosis is associated with a decreased risk of cancer-specific and all-cause mortality.Methods: This study was conducted linking four databases from the United Kingdom. A cohort of men newly diagnosed with nonmetastatic prostate cancer with a history of treated type II diabetes, between April 1, 1998 and December 31, 2009, was followed until October 1, 2012. Nested case-control analyses were performed for cancer-specific mortality and all-cause mortality, in which exposure was defined as use of metformin during the time to risk-set. Conditional logistic regression was used to estimate adjusted rate ratios (RR) of each outcome with 95% confidence intervals (CI).Results: The cohort consisted of 935 men with prostate cancer and a history of type II diabetes. After a mean follow-up of 3.7 years, 258 deaths occurred, including 112 from prostate cancer. Overall, the post-diagnostic use of metformin was not associated with a decreased risk of cancer-specific mortality (RR, 1.09; 95% CI, 0.51-2.33). In a secondary analysis, a cumulative duration 938 days was associated with an increased risk (RR, 3.20; 95% CI, 1.00-10.24). The post-diagnostic use of metformin was not associated with all-cause mortality (RR, 0.79; 95% CI, 0.50-1.23).Conclusion: The use of metformin after a prostate cancer diagnosis was not associated with an overall decreased risk of cancer-specific and all-cause mortality.Impact: The results of this study do not support a role for metformin in the prevention of prostate cancer outcomes. Cancer Epidemiol Biomarkers Prev; 23(10); 2111-8. Ó2014 AACR.

Impact of metformin on clinical outcomes among men with prostate cancer: a systematic review and meta-analysis

“…Five studies were conducted in the United States (US) (13, 14, 27-29), two in the United Kingdom (UK) (30, 31) and one in Canada (15), while, the last study utilized data from both UK and US (32). Five studies restricted the study sample to men with diabetes and prostate cancer (13, 15, 27, 30, 31), while four studies included sample of men with prostate cancer with presence or absence of diabetes (14, 28, 29, 32). The metformin users ranged from 32.6% (14) to 63.5% (28) among men with prostate cancer.…”

“…Except one nested case-control study (31), the other eight studies utilized a retrospective cohort design (13-15, 27-30, 32). The one nested case-control study utilized Cancer Registry linked Medical records (31).…”

“…Except one nested case-control study (31), the other eight studies utilized a retrospective cohort design (13-15, 27-30, 32). The one nested case-control study utilized Cancer Registry linked Medical records (31). Out of eight retrospective studies, four studies utilized single-institutional based electronic medical records (13, 14, 28, 29); two studies utilized multicenter electronic medical data from primary care practice (30, 32), one study utilized data from the Veterans Affairs Medical Centers (27), and the last study utilized amalgamation of population-based administrative claims data with other clinical databases (15).…”

“…Only four studies explicitly mentioned the ascertainment of diabetes via diagnostic codes (15, 30, 31) or self-report (13). Three studies mentioned the ascertainment of prostate cancer via diagnostic codes (15, 30) and biopsy-proven prostate cancer diagnosis by a trained pathologist (29).…”

Prostate cancer

“…There is no doubt that PC is a disease with several unclear prevention targets (e.g., Metformin). 36 To date, compelling evidence exists only for medications that reduce PC incidence; there are no convincing data showing that a dietary supplement can achieve PC reduction. Finally, lifestyle changes, including exercise and diets low in saturated fat with increased antioxidants and omega 3 and 6 fatty acids, are healthy habits that can prevent PC and other comorbidities.…”