The effect of metformin and thiazolidinedione use on lung cancer in diabetics

BMC Cancer (Impact Factor: 3.36). 09/2012; 12(1):410. DOI: 10.1186/1471-2407-12-410
Source: PubMed


Metformin and the thiazolidinediones (TZDs) may have a protective effect against the development of lung cancer.

Patients with diabetes mellitus (DM) were identified from the electronic medical records of the Cleveland Clinic. Diabetics with lung cancer were identified then verified by direct review of their records. Control subjects were matched with cancer subjects 1:1 by date of birth, sex, and smoking history. The frequency and duration of diabetic medication use was compared between the groups. The cancer characteristics were compared between those with lung cancer who had and had not been using metformin and/or a TZD.

93,939 patients were identified as having DM. 522 lung cancers in 507 patients were confirmed. The matched control group was more likely to have used metformin and/or a TZD (61.0% vs. 41.2%, p < 0.001 for any use; 55.5% vs. 24.6%, p < 0.001 for >24 months vs. 0–12 months). In the group with lung cancer, those who had used metformin alone had a different histology distribution than those who received neither metformin nor a TZD, were more likely to present with metastatic disease (40.8% vs. 28.2%, p = 0.013), and had a shorter survival from the time of diagnosis (HR 1.47, p < 0.005).

The use of metformin and/or the TZDs is associated with a lower likelihood of developing lung cancer in diabetic patients. Diabetics who develop lung cancer while receiving metformin may have a more aggressive cancer phenotype.


Available from: Anil K Jain, Jan 28, 2014
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    • "Meta-analysis of all 8 observational studies reported that the metformin use was associated with a statistically significant 15% reduction in lung cancer incidence (OR 0.85, 95% CI 0.77 to 0.92 P = 0.003 for heterogeneity) (Figure 2a) [9], [10], [12], [13], [15], [17], [33], [35]. The summary OR of 7 cohort studies was 0.87 (95% CI 0.81 to 0.93). "
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    ABSTRACT: Background 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. Methods We 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. Results Analysis 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. Conclusions This 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.
    PLoS ONE 06/2014; 9(6):e99577. DOI:10.1371/journal.pone.0099577 · 3.23 Impact Factor
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    • "Epidemiological studies (8–10) first suggested a link between metformin and cancer prevention by demonstrating a lower incidence of death from cancer in patients with diabetes mellitus treated with metformin than those treated with other antidiabetic agents. These studies were followed by clinical observations, suggesting a link between metformin and increased pathologically complete response rate by induction chemotherapy in patients with breast cancer (10) as well as lower incidence rate of metastasis and a reduced risk of death in patients with lung cancer (11). These findings triggered a number of in vitro and in vivo experiments, revealing its antiproliferative properties in a variety of cancers (12–20). "
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    International Journal of Oncology 10/2013; 43(6). DOI:10.3892/ijo.2013.2120 · 3.03 Impact Factor
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    • "A meta-analysis completed this past year confirms a small, but significant decreased risk of lung (and other) cancers in diabetics treated with thiazolidinediones [93]. A review of patients with diabetes at the Cleveland Clinic found that those who had not been treated with metformin (see mTOR inhibitors section below) and/or thiazolidinediones were more likely to develop lung cancer [94]. An ongoing trial at the Denver VA is evaluating the effect of pioglitazone on lung cancer incidence in smokers [95]. "
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    Cancers 03/2013; 5(1):131-48. DOI:10.3390/cancers5010131
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