Abstract
Several preclinical and observational studies have shown that anti-diabetic medications (ADMs) may modify the risk of lung cancer. We performed a systematic review and meta-analysis evaluating the effect of metformin, sulfonylureas (SUs), thiazolidinediones (TZDs), and insulin on the risk of lung cancer in patients with diabetes mellitus (DM). We conducted a systematic search of Pubmed and Web of Science, up to August 20, 2013. We also searched the Conference Proceedings Citation Index (CPCI) and China National Knowledge Infrastructure (CNKI) for abstracts from major meetings. Fixed or random effect pooled measures were selected based on heterogeneity among studies, which was evaluated using Q test and the I2 of Higgins and Thompson. Meta-regression was used to explore the sources of between-study heterogeneity. Publication bias was analyzed by Begg's funnel plot and Egger's regression test. Associations were assessed by odds ratios (ORs) with 95% confidence intervals (CIs). A total of 15 studies (11 cohort, 4 case-control) were included in this meta-analysis. In observational studies no significant association between metformin (n=11 studies; adjusted OR=0.99, 95%CI: 0.87-1.12), SUs (n=5 studies; adjusted OR=0.98, 95%CI: 0.79-1.22), or TZDs (n=7 studies; adjusted OR=0.92, 95%CI: 0.75-1.13), insulin (n=6 studies; adjusted OR=1.13, 95%CI: 0.79-1.62) use and risk of developing lung cancer was noted. There was considerable inherent heterogeneity between studies not explained by study design, setting, or location. Meta-analysis of existing studies does not support a protective or harmful association between ADMs use and risk of lung cancer in patients with DM. There was considerable heterogeneity across studies, and future, well-designed, prospective studies would be required for better understanding of any association.
Highlights
Lung cancer is one of the leading causes of cancer-related mortality worldwide and accounts for approximately 30% of cancer deaths in US (Jemal et al, 2010)
There was no evidence of significant publication bias, both quantitatively (p=0.223 for metformin, p=0.357 for SUs, p=0.297 for TZDs, and p=0.818 for insulin) and qualitatively, on visual inspection of the funnel plot. In this meta-analysis of 15 studies analyzing the effect of conventional anti-diabetic medications (ADMs) on modifying the risk of lung cancer in patients with diabetes mellitus (DM), we found that metformin use was not associated with a decreased risk of lung cancer, though there was a slight trend towards lower risk
The other three ADMs (SUs and TZDs, insulin) use were not associated with an increased risk of lung cancer
Summary
Lung cancer is one of the leading causes of cancer-related mortality worldwide and accounts for approximately 30% of cancer deaths in US (Jemal et al, 2010). Despite advances in early diagnosis and treatment modalities, prognosis remains poor; the five-year survival rate is only about 15% (Mulshine et al, 2005). Individuals at risk for developing lung cancer can be identified by clinical epidemiologic factors (Bach et al, 2003; Spitz et al, 2007; Cassidy et al, 2008; Tammemagi et al, 2011; Ding et al, 2013) and it has been well established that tobacco smoking is the most important cause of lung cancer, accounting for 85%-90% of all cases in the world (Ruano-Ravina et al, 2003; Tyczynski et al, 2003). The prevention of lung cancer is of utmost importance and urgent efforts are needed to identify measures, including drug treatment that may be effective in reducing the lung cancer risk
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