Effects of Metformin Dose on Cancer Risk Reduction in Patients with Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

Lin, Hsiu Chen; Kachingwe, Baxter Hepburn; Cheng, Hui; Uang, Yow Shieng; Wang, Li‐Hsuan

doi:10.1002/phar.1334

Cited by 33 publications

(24 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, inflammation is an established component of carcinogenesis, and, since HF is characterized by chronic inflammation and neurohormonal activation, it may be speculated that chronic inflammation plays a role in the increased risk of development of cancer in HF. This is supported by growing evidence suggesting an increased risk of cancer among patients with other chronic diseases with an inflammatory component such as type 2 diabetes, where breast, colorectal, pancreatic, and oesophageal cancer have been suggested to be more frequent and to be associated with a poor prognosis . At the tissue level, an association between chronic inflammation and cancer has also been demonstrated for inflammatory bowel disease and colorectal cancer …”

Section: Discussionmentioning

confidence: 84%

Incidence of cancer in patients with chronic heart failure: a long‐term follow‐up study

Banke

Schou

Videbæk

et al. 2016

European J of Heart Fail

189

183

View full text Add to dashboard Cite

AimsWith improvement in survival of chronic heart failure (HF), the clinical importance of co-morbidity is increasing. The aim of this study was to assess the incidence and risk of cancer and all-cause mortality in a large Danish HF cohort. Methods and resultsA total of 9307 outpatients with verified HF without a prior diagnosis of cancer (27% female, mean age 68 years, 89% with LVEF <45%) were included in the study. A diagnosis of any cancer and all-cause mortality was obtained from Danish national registries. Outcome was compared with the general Danish population. Overall and type-specific risk of cancer was analysed in an adjusted Poisson and Cox regression analysis. The 975 diagnoses of cancer in the HF cohort and 330 843 in the background population corresponded to incidence rates per 10 000 patient-years of 188.9 [95% confidence interval (CI) 177.2-200.6] and 63.0 (95% CI 63.0-63.4), respectively. When stratified by age, incidence rates were increased in all age groups in the HF cohort. Risk of any type of cancer was increased, with an incidence rate ratio of 1.24 (95% CI 1.15-1.33, c < 0.0001). Type-specific analysis demonstrated an increased hazard ratio for all major types of cancer except for prostate cancer.

show abstract

Section: Discussionmentioning

confidence: 84%

Incidence of cancer in patients with chronic heart failure: a long‐term follow‐up study

Banke

Schou

Videbæk

et al. 2016

European J of Heart Fail

189

183

View full text Add to dashboard Cite

show abstract

“…Population-based studies show that metformin, widely used for the treatment of type 2 diabetes mellitus, [8][9][10] is associated with a dose-dependent reduction in cancer risk. 21 Previous studies demonstrated that metformin restrained prostate cancer cell proliferation, migration, and invasion and enhanced apoptosis. 13,22 These findings are consistent with our results.…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression

Chen

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Metformin has been reported to inhibit the growth of various types of cancers, including prostate cancer. Yet the mode of anti-cancer action of metformin and the underlying mechanisms remain not fully elucidated. We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells. In this report, metformin treatment significantly inhibited the proliferation and colony formation of prostate cancer cells, in a dose-and time-dependent manner. Meanwhile, Metformin markedly suppressed migration and invasion and induced apoptosis of both LNCaP and PC3 cancer cells. Metformin also reduced PC3 tumor growth in BALB/c nude mice in vivo. Furthermore, metformin treatment was associated with higher PEDF expression in both prostate cancer cells and tumor tissue. Taken together, metformin inhibits prostate cancer cell proliferation, migration, invasion and tumor growth, and these activities are mediated by upregulation of PEDF expression. These findings provide a novel insight into the molecular functions of metformin as an anticancer agent.Abbreviations: PEDF, pigment epithelium-derived factor; AMPK, 5 0 -AMP-activated protein kinase; mTOR, mammalian target of rapamycin; IL8, interleukin8; MAPK, mitogen-activated protein kinase; Met, metformin; qPCR, quantitative polymerase chain reaction; PBS, fetal bovine serum; CCK8, Cell Counter Kit-8; PBS, phosphate-buffered saline solution; PtdIns, propidium iodide; SD, standard deviation

show abstract

“…Metformin has been demonstrated to exert anticancer effects in several types of cancer, including those affecting the liver, colon, breast, pancreas, and prostate ( 7 ). However, the utility of metformin in the prevention and treatment of bladder cancer has not been specifically investigated.…”

Section: Discussionmentioning

confidence: 99%

“…There has been considerable interest in the antitumor properties of metformin. Lin et al ( 7 ) reported that the magnitude of cancer risk reduction and prolonged cancer onset times produced by metformin in patients with type 2 diabetes depended on the dose of metformin. Therefore, we determined the potential association of a history of DM and glycemic control with tumor characteristics and recurrence-free survival (RFS) and progression-free survival (PFS) among patients who underwent transurethral resection (TUR) for NMIBC.…”

Section: Introductionmentioning

confidence: 99%

Impact of Glycemic Control and Metformin Use on the Recurrence and Progression of Non-Muscle Invasive Bladder Cancer in Patients with Diabetes Mellitus

et al. 2016

View full text Add to dashboard Cite

The purpose of the present study was to determine the potential relationships of glycemic control and use of metformin with non-muscle invasive bladder cancer characteristics. We reviewed data from 645 patients with non-muscle invasive bladder cancer between January 2004 and May 2015. We analyzed the association of pre and post-operative glycemic control and use of metformin with clinical characteristics of bladder tumors. We also analyzed the association of glycemic control and use of metformin with recurrence-free and progression-free survivals. Diabetes mellitus patients showed decreased recurrence-free survival (hazard ratio 1.42; 95% confidence interval 1.1–1.9; P = 0.021) and progression-free survival (hazard ratio 1.79; 95% confidence interval 1.1–2.8; P = 0.013). Diabetes mellitus patients with a HbA1c ≥ 7.0% demonstrated a higher rate of progression (P = 0.026). Kaplan-Meier analysis showed that progression-free survival rate was associated with poor baseline glycemic control (P = 0.026) and post-operative glycemic control (P = 0.025). However, use of metformin had no impact on the recurrence (P = 1.00) and progression (P = 0.282). In conclusion, poor baseline and post-operative glycemic control was related with shorter progression-free survival of patients with non-muscle invasive bladder cancer. Use of metformin had no impact on the recurrence and progression. Therefore, tight glycemic control and close follow-up for bladder tumor may be beneficial in patients with poor glycemic control.

show abstract

Effects of Metformin Dose on Cancer Risk Reduction in Patients with Type 2 Diabetes Mellitus: A 6-Year Follow-up Study

Abstract: The magnitude of cancer risk reduction and prolonged cancer onset times produced by metformin in patients with type 2 diabetes depended on the dose of metformin, regardless of whether metformin was used alone or combined with other antidiabetic drugs.

Cited by 33 publications

References 49 publications

Incidence of cancer in patients with chronic heart failure: a long‐term follow‐up study

Incidence of cancer in patients with chronic heart failure: a long‐term follow‐up study

Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression

Impact of Glycemic Control and Metformin Use on the Recurrence and Progression of Non-Muscle Invasive Bladder Cancer in Patients with Diabetes Mellitus

Contact Info

Product

Resources

About