Abstract
BackgroundAccumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes.MethodsWe performed a meta-analysis using EMBASE, MEDLINE and Web of Science to search randomised controlled trials (RCTs), cohort studies, and case-control studies published up to October 2013 that assessed the effects of metformin, sulfonylurea, TZDs or insulin on lung cancer risk in subjects with diabetes. Fixed and random effects meta-analysis models were used, and the effect size was expressed as a summary odds ratio (OR) with 95% confidence intervals (CI). The Grades of Research, Assessment, Development and Evaluation (GRADE) approach was applied to define the quality of the evidence.ResultsAnalysis of 15 studies (11 cohort studies, 2 case-control studies, and 2 RCTs) showed that metformin use was associated with a 15% reduction in risk of lung cancer (OR 0.85, 95% CI 0.77 to 0.92), but this finding was not supported by sub-analysis of smoking-adjusted studies (OR 0.84, 95% CI 0.61 to 1.06). Moreover, sulfonylurea or TZDs use was not associated with increased or decreased lung cancer risk, respectively (OR 1.10, 95% CI 0.93 to 1.26), (OR 0.86, 95% CI 0.70 to 1.02). Higher lung cancer risk was related to insulin (OR 1.23, 95% CI 1.10 to 1.35). However, all data from RCTs failed to demonstrate a statistically significant effect.ConclusionsThis analysis demonstrated that metformin use may reduce lung cancer risk in patients with diabetes but not in a smoking-adjusted subgroup and that insulin use may be associated with an increased lung cancer risk in subjects with diabetes.
Highlights
Lung cancer is the leading cause of cancer-related death both in the USA and around the world [1]
Selection criteria All potentially relevant studies were retrieved and assessed for inclusion according to the following criteria: (1) study must have evaluated lung cancer risk in patients with diabetes on the basis of type of hypoglycaemic agent; (2) study design must have been randomised controlled trials (RCT), case–control or cohort; (3) study must have reported the hazard ratio (HR) or odds ratio (OR); and (4) population consisted of adult patients
There were five Taiwanese studies from the same cohort, and one of these was included in the analysis for metformin, sulfonylureas and insulin, while another was analysed for TZDs
Summary
Lung cancer is the leading cause of cancer-related death both in the USA and around the world [1]. Diabetes has been established as an independent risk factor for lung cancer [3].Increasing evidence has shown that conventional glucoselowering drugs such as insulin, insulin sensitisers and secretagogues, may influence the risk of cancer. Several observational studies have suggested that the use of metformin and TZDs is associated with a decreased risk of lung cancer compared with other glucoselowering drugs [9] [10] [11]. Accumulating evidence suggests that hypoglycaemic agents influence lung cancer risk in patients with diabetes. It remains to be fully elucidated whether conventional hypoglycaemic agents (metformin, sulfonylureas, thiazolidinediones [TZDs] or insulin) affect lung cancer incidence in patients with diabetes
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