Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis

Nie, Sheng; Chen, Hui; Zhuang, Maoqiang; Lu, Ming

doi:10.7314/apjcp.2014.15.16.6863

Cited by 19 publications

(16 citation statements)

References 52 publications

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“…However, there are also a few studies that report no effect between metformin and risk of lung cancer. Nie et al reported that in 11 studies found, in a systematic search up to August 2013, there was no significant association between diabetes mellitus patients receiving metformin and lung cancer risk (OR = 0.99, 95% CI: 0.87–1.12) [85]. Similarly, Franciosi et al reported that in two randomized controlled studies (RCTs) and four observational studies, there was no significant association between metformin and lung cancer risk in RCTs and only a marginal non-significant reduction was found in observational studies in diabetes mellitus patients (OR = 0.83, 95% CI: 0.64–1.06, p = 0.13) [86].…”

Section: Effects Of Metformin In Lung Cancer: Human Studiesmentioning

confidence: 99%

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Yousef

Tsiani

2017

Cancers

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Cancer cells display enhanced growth rates and a resistance to apoptosis. The ability of cancer cells to evade homeostasis and proliferate uncontrollably while avoiding programmed cell death/apoptosis is acquired through mutations to key signaling molecules, which regulate pathways involved in cell proliferation and survival and these mutations allow them to develop resistance to many chemotherapeutic agents, highlighting the need for development of new potent anti-cancer agents. Metformin has long been used as a treatment for type 2 diabetes and has recently attracted attention as a potential agent to be used in the treatment of cancer. The present review summarizes the existing in vitro and in vivo animal studies focusing on the anti-lung cancer effects of metformin and its effects on key proliferative and anti-apoptotic signaling pathways.

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Section: Effects Of Metformin In Lung Cancer: Human Studiesmentioning

confidence: 99%

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Yousef

Tsiani

2017

Cancers

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“…Zhang et al pooled the data from 4 studies and showed a significantly lower risk associated with metformin use (pooled relative risk: 0.71, 95% confidence interval: 0.55-0.95, P =0.02) [24]. However, by including 15 (11 cohort and 4 case-control) observational studies, Nie et al reported a null association with an adjusted odds ratio of 0.99 (95% confidence interval: 0.87-1.12) [25]. The meta-analysis by Wu et al (including 15 studies: 11 cohort, 2 case-control and 2 randomized controlled trials) suggested a 15% risk reduction (odds ratio 0.85, 95% confidence interval: 0.77-0.92), but this could not be demonstrated in smoking-adjusted subgroup [26].…”

Section: Introductionmentioning

confidence: 99%

Metformin and lung cancer risk in patients with type 2 diabetes mellitus

Tseng

2017

Oncotarget

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This study evaluated whether metformin might reduce lung cancer risk. The reimbursement database of the Taiwan's National Health Insurance was used. A sample of 15414 never users and 280159 ever users of metformin (original sample) and a 1:1 matched-pairs of ever and never users (n=15414 in each group, matched sample) were recruited from patients with newly diagnosed type 2 diabetes mellitus during 1999-2005. They were followed until December 31, 2011. Cox regression incorporated with the inverse probability of treatment weighting using propensity score was used to estimate hazard ratios. Results showed that the respective incidence of lung cancer in ever and never users was 173.36 and 292.65 per 100000 person-years in the original sample; and was 211.71 and 292.65, respectively, in the matched sample. The overall hazard ratios (95% confidence intervals) of 0.586 (0.509-0.674) in the original sample and 0.717 (0.584-0.881) in the matched sample suggested a significantly lower risk among metformin users. Hazard ratios comparing the first (<22.60 months), second (22.60-46.67 months) and third (>46.67 months) tertile of cumulative duration of metformin use to never users was 1.163 (1.005-1.348), 0.612 (0.526-0.711) and 0.176 (0.148-0.210), respectively, in the original sample; and was 1.465 (1.131-1.897), 0.758 (0.566-1.016) and 0.228 (1.460-0.357) in the respective tertile of the matched sample. Sensitivity analyses after excluding patients with certain risk factors of cancer and subgroup analyses supported a favorable effect of metformin. In conclusion, metformin use may reduce lung cancer risk in patients with type 2 diabetes mellitus.

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“…With the development of living standard, the morbidity of type 2 diabetes mellitus (T2DM) increases rapidly (2). At present, numerous studies have found that T2DM is a systemic disease, and associated with the progression of several human malignant tumors (3,4). …”

Section: Introductionmentioning

confidence: 99%

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression

et al. 2017

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Abstract. Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.

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Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis

Cited by 19 publications

References 52 publications

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies

Metformin and lung cancer risk in patients with type 2 diabetes mellitus

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression

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