The effect of metformin on lung cancer risk and survival in patients with type 2 diabetes mellitus: A meta‐analysis

Xiao, Kang; Liu, Fengxi; Liu, Juan; Xu, Jiachao; Wu, Qiu-yun; Li, Xiao

doi:10.1111/jcpt.13167

Cited by 41 publications

(33 citation statements)

References 36 publications

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“…Most of the included studies in our meta-analysis have adjusted these factors, which may therefore weaken the association between MetS and Lung cancer incidence. Moreover, accumulating evidence showed that treatments against the components of Mets, such as the use of metformin, may lead to a reduced risk of lung cancer incidence [ 43 ]. Whether these factors may confound the association between MetS and Lung cancer risk also deserves further investigation.…”

Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and the incidence of lung cancer: a meta-analysis of cohort studies

Qiao

et al. 2020

Diabetol Metab Syndr

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Background Metabolic syndrome (MetS) has been related to the pathogenesis of variety categories of cancers. This meta-analysis aimed to determine the association between MetS and the incidence of lung cancer. Methods Relevant cohort studies were identified by search of PubMed, Embase, and Cochrane’s Library databases. Cochrane’s Q test and I2 statistic were used to analyze the heterogeneity. Random-effect model which incorporates the potential heterogeneity was used for the meta-analysis. Results Five cohort studies with 188,970 participants were included. A total of 1,295 lung cancer cases occurred during follow-up. Meta-analyses showed that neither MetS defined by the revised NCEP-ATP III criteria (hazard ratio [HR]: 0.94, 95% confidence interval [CI]: 0.84 to 1.05, p = 0.25; I2 = 0) nor the IDF criteria (HR: 0.82, 95% CI: 0.61 to 1.11, p = 0.20; I2 = 0) was associated with an affected risk of lung cancer. Subgroup analyses showed consistent results in women and in men, in studies performed in Asian and non-Asian countries, and in prospective and retrospective cohorts (p all > 0.05). Meta-analysis limited to studies with the adjustment of smoking status also showed similar results (HR: 0.91, 95% CI: 0.80 to 1.05, p = 0.21; I2 = 0). No publication bias was detected based on the Egger regression test (p = 0.32). Conclusions Current evidence from cohort studies does not support that MetS is an independent risk factor for the incidence of lung cancer.

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Section: Discussionmentioning

confidence: 99%

Metabolic syndrome and the incidence of lung cancer: a meta-analysis of cohort studies

Qiao

et al. 2020

Diabetol Metab Syndr

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“…Subsequently, metformin has been investigated as an antitumor agent for various cancers, including lung cancer ( Zhang and Li, 2014 ; Coyle et al, 2016 ). Recently, meta-analyses have suggested that metformin intake may be associated with a survival benefit among patients with lung cancer and concurrent diabetes ( Cao et al, 2017 ; Zhang et al, 2018 ; Xiao et al, 2020 ). In addition, clinical studies have identified combinational therapies of metformin and antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)] in lung cancer, both in diabetic and non-diabetic subjects.…”

Section: Introductionmentioning

confidence: 99%

Metformin Adjunct With Antineoplastic Agents for the Treatment of Lung Cancer: A Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies

et al. 2021

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Objective: Resistance to anticancer agents ensures a poor prognosis in patients with lung cancer. Metformin could enhance the anticancer effects of standard antineoplastic agents [traditional chemotherapy drugs, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), or immune checkpoint inhibitors (ICIs)]; however, it is unclear whether metformin can be combined with antineoplastic agents in the treatment of lung cancer. To explore the efficacy of combinational strategies, we performed a systematic review and meta-analysis for diabetic and non-diabetic patients with lung cancer.Method: An electronic literature search was performed to obtain relevant randomized controlled trials (RCTs) and observational cohort studies. Hazard ratios (HR) with 95% confidence intervals (CI) of overall survival (OS) and progression-free survival (PFS) outcomes were extracted. Subgroup analysis by antineoplastic agents, study type, histology and clinical stage were investigated.Results: 14 studies (three RCTs and eleven observational cohort studies) consisting 3,856 patients were included in the meta-analysis. Compared to standard antineoplastic agents alone (traditional chemotherapy drugs, EGFR-TKIs or ICIs), the antineoplastic agents combined with metformin significantly improved OS (HR 0.73, 95% CI 0.66–0.81, p < 0.00001) and PFS (HR 0.72, 95% CI 0.59–0.88, p = 0.001); a similar association was found in observational evidence. Limited data from RCTs showed no differences in OS or PFS.Conclusion: Metformin plus antineoplastic agents may improve survival outcomes of patients with lung cancer. Further investigation is needed.

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“…The effects of metformin in NSCLC may also be in uenced by ethnicity of the patients. In a recent metaanalysis (Xiao et al 2020), lung cancer incidence was reduced in T2D patients treated with metformin compared to those without only in studies including Asian patients, but not among European patients.…”

Section: Discussionmentioning

confidence: 95%

Concurrent Metformin Use and Survival Among Finnish Non-Small Cell Lung Cancer Patients Treated With EGFR TKIs

Tiainen

Iivanainen

Alanen

et al. 2021

Preprint

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Purpose Many studies have shown correlation between metformin use and lower incidence and improved outcomes of lung cancer. We investigated the potential association between metformin use and survival among Finnish non-small cell lung cancer (NSCLC) patients treated with EGFR TKIs. Methods Nationwide registries were utilized to identify all the patients with use of EGFR TKIs in NSCLC between 2011–2016, and 1242 patients were included in further analyses. Data related to cancer, survival, and drug purchases were combined with personal identity codes. Concurrent use of diabetes medications was defined as their purchase +/-120 days from the first purchase of EGFR TKI. The impact of diabetes medication use was investigated separately in the whole and in the EGFR mutant type cohort (n = 481). Results Concurrent metformin use was found in 10 % (n = 124) and use of other diabetes medication in 5 % (n = 60) of the patients. In the whole patient cohort, metformin use did not associate with survival but in the EGFR mutant type cohort a non-significant trend for higher mortality was found (HR 1.42, 95% CI 0.99–2.02). Metformin use associated also with a shorter EGFR TKI treatment duration (HR 1.26, 95 % CI 1.04–1.52). The use of other diabetes medication than metformin did not associate with survival or EGFR TKI treatment duration. Conclusion Concomitant metformin use associated with a shorter EGFR TKI treatment duration, however, no statistically significant correlation with survival was found. Ethnicity, comorbidities, and metformin dosage may influence on the associations found between metformin use and EGFR TKI treatment responses.

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The effect of metformin on lung cancer risk and survival in patients with type 2 diabetes mellitus: A meta‐analysis

Cited by 41 publications

References 36 publications

Metabolic syndrome and the incidence of lung cancer: a meta-analysis of cohort studies

Metabolic syndrome and the incidence of lung cancer: a meta-analysis of cohort studies

Metformin Adjunct With Antineoplastic Agents for the Treatment of Lung Cancer: A Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies

Concurrent Metformin Use and Survival Among Finnish Non-Small Cell Lung Cancer Patients Treated With EGFR TKIs

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