The influence of antidiabetic medications on the development and progression of prostate cancer

Hitron, Anna; Adams, Val R.; Talbert, Jeffery; Steinke, Doug

doi:10.1016/j.canep.2012.02.005

Cited by 34 publications

(23 citation statements)

References 48 publications

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“…Overall, the results of this study are inconsistent with the favorable effects of metformin on neoplasia observed in previous laboratory models (3,4), and contrast with some of the results of the observational studies conducted on this topic (7)(8)(9)(10)(11)(12). Indeed, of the six observational studies conducted to date (7)(8)(9)(10)(11)(12), only three found a statistically significant decreased risk of prostate cancer outcomes (8,10,11).…”

Section: Discussioncontrasting

confidence: 99%

“…However, these studies had important methodologic shortcomings. In particular, three of these studies had immortal time bias (8)(9)(10). This bias has been previously described in this literature (13), and likely exaggerated the potential benefits of metformin on prostate cancer outcomes in the two studies reporting strong decreased risks (8,10).…”

Section: Introductionmentioning

confidence: 61%

“…Indeed, of the six observational studies conducted to date (7)(8)(9)(10)(11)(12), only three found a statistically significant decreased risk of prostate cancer outcomes (8,10,11). However, these studies had several methodologic shortcomings.…”

Section: Discussionmentioning

confidence: 99%

“…However, there has been renewed interest in the effect of this drug on cancer outcomes in patients with prostate cancer. To date, six observational studies have investigated the effects of metformin on cancerrelated mortality, distant metastasis, and all-cause mortality in men diagnosed with prostate cancer (7)(8)(9)(10)(11)(12). In three studies, the use of metformin was associated with strong decreased risks (ranging between 24% and 80% risk reductions) of several prostate cancer outcomes (8,10,11), whereas the other three studies reported nonsignificant findings (7,9,12).…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, none of the six observational studies accounted for latency and reverse causality (7)(8)(9)(10)(11)(12), a necessary consideration for studies investigating cancer outcomes. Finally, three studies did not assess the effects of metformin duration and dose to determine whether there was a dose-response relationship between the use of this drug and incidence of the different prostate cancer outcomes (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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

Bensimon

Yin

Suissa

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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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.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bensimon

Yin

Suissa

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The effects of nonspecific HIF1α inhibitors on development of castrate resistance and metastases in prostate cancer

et al. 2014

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Expression of hypoxia-inducible factor (HIF)1α increases the risk of castrate-resistant prostate cancer (CRPC) and metastases in patients on androgen deprivation therapy (ADT) for prostate cancer (PC). We aimed to investigate the effects of nonspecific HIF1α inhibitors (Digoxin, metformin, and angiotensin-2 receptor blockers) on development of CRPC and metastases while on ADT. A retrospective review of prospectively collected medical records was conducted of all men who had continuous ADT as first-line therapy for CRPC at the Austin Hospital from 1983 to 2011. Association between HIF1α inhibitor medications and time to develop CRPC was investigated using actuarial statistics. Ninety-eight patients meeting the criteria were identified. Eighteen patients (21.4%) were treated with the nonspecific HIF1α inhibitors. Both groups had similar characteristics, apart from patients on HIF1α inhibitors being older (70 years vs. 63.9 years). The median CRPC-free survival was longer in men using HIF1α inhibitors compared to those not on inhibitors (6.7 years vs. 2.7 years, P = 0.01) and there was a 71% reduction in the risk of developing CRPC (HR 0.29 [95% CI 0.10–0.78] P = 0.02) after adjustment for Gleason score, age, and prostate-specific antigen (PSA). The median metastasis-free survival in men on HIF1α inhibitors was also significantly longer compared to those on no inhibitors (5.1 years vs. 2.6 years, P = 0.01) with an 81% reduction in the risk of developing metastases (HR 0.19 [CI 0.05–0.76] P = 0.02) after adjustment for Gleason score, age, and PSA. Nonspecific HIF1α inhibitors appear to increase the progression-free survival and reduce the risk of developing CRPC and metastases in patients on continuous ADT.

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Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta‐analysis

Deng

Yang

Tang

et al. 2015

Diabetes Metabolism Res

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The influence of antidiabetic medications on the development and progression of prostate cancer

Abstract: Future studies should be conducted to further evaluate the effects of anti-diabetic medications on tumor grade and time to prostate cancer progression.

Cited by 34 publications

References 48 publications

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

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

The effects of nonspecific HIF1α inhibitors on development of castrate resistance and metastases in prostate cancer

Association between metformin therapy and incidence, recurrence and mortality of prostate cancer: evidence from a meta‐analysis

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