The Clinical Effect of Metformin on the Survival of Lung Cancer Patients with Diabetes: A Comprehensive Systematic Review and Meta-analysis of Retrospective Studies

Abstract

Preclinical investigations have revealed an anti-cancer effect of metformin. Several studies of metformin treatment have demonstrated the improved clinical outcomes of lung cancer patients with diabetes; however, the results have been inconsistent among studies. Our systematic review and meta-analysis aimed to summarize the up-to-date effects of metformin on diabetic lung cancer patients.A systematic search was performed for studies published. Then, these studies were evaluated for inclusion, and relevant data was extracted. The summary risk estimates for the associations of metformin treatment with overall survival (OS) and progression-free survival (PFS) were analyzed using random/fixed-effects models. Analyses stratified by histological type were also conducted. Based on the 10 studies included in our analysis, metformin treatment was found to significantly improve survival, corresponding to reductions of 23% and 47% in OS [hazard ratio (HR)=0.77, 95% confidence interval (95%CI)=0.66-0.9, p=0.001] and PFS (HR=0.53, 95%CI=0.41-0.68, p<0.001), respectively. In addition, significant improvements in the OS for non-small cell lung cancer (NSCLC) (HR=0.77, 95%CI=0.71-0.84, p=0.002) and small cell lung cancer (SCLC) (HR=0.52, 95%CI=0.29-0.91, p=0.022) were observed in association with metformin treatment in analysis stratified by histological type. This stratified analysis also revealed a significant improvement in PFS for both NSCLC (HR=0.53, 95%CI=0.39-0.71, p<0.001) and SCLC (HR=0.54, 95%CI=0.34-0.84, p=0.007). We found that metformin treatment significantly improved the OS and PFS of diabetic lung cancer patients, and our findings suggest that metformin might be an effective treatment option for diabetic patients with lung cancer.

Cancer survival in patients from a hospital-based cancer registry, China

“…Clinical survival reports are used to summarize the therapeutic effects of care from clinics or hospitals 7 . PBCR survival can reflect the overall situation of cancer diagnosis and treatment, and even the general situation of health care 4 - 6 ; while survival case series could reflect overall treatment effects in a particular medical department or the use of a certain treatments 7 , 8 . However, reports reflecting comprehensive treatment outcomes of a specific hospital are rare.…”

The prognostic value of metformin for advanced non-small cell lung cancer: a systematic review and meta-analysis

“…Based on three current meta-analyses (one based on systematic review), potential efficacy of Metformin to prolong overall survival (OS) could be found in SCLC consistently. The pooled hazard ratio (HR) was 0.52 (P<0.05) in the three studies (7)(8)(9). However, for NSCLC their outcomes were controversial.…”

A risk stratification model based on four novel biomarkers predicts prognosis for patients with renal cell carcinoma

“…It has been previously demonstrated that inhibitors targeting mitochondrial oxidative phosphorylation such as biguanides induce death of RCC cells and may become therapeutic options to overcome the disastrous consequences of SOD2abundance in RCC cells [9]. Furthermore, the antitumor effect of biguanides like metformin in patients with diabetes has been demonstrated in several carcinomas [23][24][25][26][27]. In order to target tumor cell mitochondria, applying biguanides to replacement therapy or drug repositioning should be proposed for patients with SOD2-abundant RCC for maintenance phase treatments after primary surgery debulking numbers of RCC cells.…”