Clinical Outcomes After Radical Prostatectomy in Diabetic Patients Treated With Metformin

Patel, Trushar; Hruby, Greg; Badani, Ketan K.; Abate‐Shen, Cory; McKiernan, James M.

doi:10.1016/j.urology.2010.03.059

Cited by 76 publications

(94 citation statements)

References 31 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%

“…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, they do highlight the need of replicating observational studies in different populations and settings. Finally, none of the six observational studies conducted on this topic considered latency (7)(8)(9)(10)(11)(12), which is necessary for any study assessing the effect of a drug on cancer outcomes. An unexpected finding of this study was the 3-fold increased risk of prostate cancer mortality (RR, 3.20; 95% CI, 1.00-10.24) associated with the highest tertile metformin cumulative duration of use.…”

Section: Discussionmentioning

confidence: 99%

“…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). However, these studies had important methodologic shortcomings.…”

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: Discussionmentioning

confidence: 99%

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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Metformin prevents DMH‐induced colorectal cancer in diabetic rats by reversing the warburg effect

Jia

Liu

et al. 2015

Cancer Medicine

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Epidemiologic studies have shown that the treatment of diabetics with metformin reduced the risk of cancer-related mortality. Here, we investigated the chemopreventive effects of metformin on dimethylhydrazine (DMH)-induced colorectal carcinogenesis in diabetic SD rats following metformin treatment and the effect on Warburg effect involved in this process. Diabetic rat models were induced with high-fat feeding in combination with a low dose of Streptozotocin (STZ) and then induce colorectal cancer with a low dose of DMH. The formation of colorectal Aberrant crypt foci (ACF) and the incidence, number and size of the tumor were measured. The proliferation indices of colonic tissues were determined through Proliferating cell nuclear antigen (PCNA) immunostaining. Then detect the expression of PK and IDH in colonic tissues using immunohistochemistry and Western blot. The enzyme activities of HK and PDH in colonic tissues were measured. The growth and expression of PK and IDH and activity of HK and PDH in cell lines LoVo and HT-29 were measured after metformin treatment. The results showed that metformin treatment significantly inhibited the formation of ACF and tumors. The proliferation index of colonic tissues was significantly decreased following metformin treatment. In addition, metformin inhibited cell growth and decreased the imbalance in the expression of the enzymes involved in glycolysis and the TCA cycle. These findings suggested that metformin might produce a synergistic colon cancer-preventative effect in diabetic patients through the regulation of the enzymes expression involved in glucose metabolism.

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Diabetes mellitus: influences on cancer risk

Szablewski

2014

Diabetes Metabolism Res

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Diabetes mellitus and cancer are common conditions, and their co-diagnosis in the same individual is not infrequent. The relative risks associated with type 2 diabetes are greater than twofold for hepatic, pancreatic, and endometrial cancers. The relative risk is somewhat lower, at 1.2-1.5-fold for colorectal, breast, and bladder cancers. In comparison, the relative risk of lung cancer is less than 1. The evidence for other malignancies (e.g. kidney, non-Hodgkin lymphoma) is inconclusive, whereas prostatic cancer occurs less frequently in male patients with diabetes. The potential biologic links between the two diseases are incompletely understood. Evidence from observational studies suggests that some medications used to treat hyperglycemia are associated with either increased or reduced risk of cancer. Whereas anti-diabetic drugs have a minor influence on cancer risk, drugs used to treat cancer may either cause diabetes or worsen pre-existing diabetes. If hyperinsulinemia acts as a critical link between the observed increased cancer risk and type 2 diabetes, one would predict that patients with type 1 diabetes would have a different cancer risk pattern than patients with type 2 diabetes because the former patients are exposed to lower levels of exogenous administered insulin. Obtained results showed that patients with type 1 diabetes had elevated risks of cancers of the stomach, cervix, and endometrium. Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes.

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Clinical Outcomes After Radical Prostatectomy in Diabetic Patients Treated With Metformin

Cited by 76 publications

References 31 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

Metformin prevents DMH‐induced colorectal cancer in diabetic rats by reversing the warburg effect

Diabetes mellitus: influences on cancer risk

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