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Title:
Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials | Acta Diabetologica
Description:
Recent epidemiological data have contributed to the formulation of the hypothesis about the long-term safety of pioglitazone, a thiazolidinedione (TZD), with respect to malignancies, in particular bladder cancer. The primary aim of this meta-analysis of randomized clinical trials, not designed a priori to test this hypothesis, was to explore whether TZDs affect the risk of cancer. A meta-analysis was performed including published and unpublished randomized trials with a duration of at least 52 weeks, enrolling patients with or without diabetes, comparing TZDs with either placebo or other drug therapies on various different outcomes. We found 22 trials reporting at least one cancer and enrolling 13,197 patients to TZD (pioglitazone: n = 3,710 and rosiglitazone: n = 9,487) and 12,359 to placebo or active comparator groups. The mean follow-up was 26.1 months. Overall, those assigned at random to TZDs had a significant reduction (MH-OR 0.85 [0.73–0.98]; p = 0.027) in the incidence of malignancies, with no significant difference in effect between pioglitazone and rosiglitazone. Specifically, subgroup analyses showed a significant reduction for rosiglitazone (MH-OR 0.82 [0.69–0.98]; p = 0.029), but not for pioglitazone (MH-OR 0.66 [0.34–1.28]; p = 0.22). In further subgroup analyses of site-specific malignancies based on the data from four trials, the risk of bladder cancer with pioglitazone (MH-OR) was 2.05 [0.84–5.02]; p = 0.12. Further, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk of bowel cancer. In contrast, pioglitazone, but not rosiglitazone, was associated with a significant reduction in breast cancer. The present meta-analysis of trials, not designed a priori to test the hypothesis, provides reassuring evidence that TZDs are not associated with risk of overall malignancies. In fact, they are compatible with the possibility of a decreased risk of cancer. In site-specific subgroup analyses, for rosiglitazone, there was a significant decreased risk of bowel cancer. Subgroup analyses for pioglitazone did not allow to exclude an increased risk of bladder cancer, while the risk of breast cancer was significantly decreased. While these data are also useful to formulate not test hypotheses, they provide somewhat more cogent evidence than the previously published epidemiological data.
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article, pubmed, cancer, google, scholar, diabetes, cas, pioglitazone, risk, patients, bladder, rosiglitazone, type, metaanalysis, randomized, trials, drug, data, thiazolidinediones, study, clinical, monami, mannucci, safety, care, trial, access, privacy, cookies, content, information, acta, test, significant, effects, agency, european, publish, research, search, results, published, matteo, dicembrini, edoardo, malignancies, tzds, mhor, subgroup, analyses,
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eu/docs/en_gb/document_library/press_release/2010/07/wc500094981 month download article/chapter gov/drugs/drugsafety/ucm226214 azienda ospedaliero-universitaria careggi parallel-group comparison trial lewis jd open-label trial site-specific subgroup analyses ppargamma-independent antitumor effects site-specific malignancies based ongoing benefit-risk review european medicines agency full article pdf privacy choices/manage cookies author information authors performed including published oral antidiabetic medication related subjects edoardo mannucci article monami anti-diabetic agents hepatology [epub ahead european economic area oral hypoglycaemic agents randomized clinical trials preferred reporting items ongoing safety review careggi teaching hospital randomised controlled trial population-based study unpublished randomized trials active comparator groups quesenberry cp jr secondary prevention versican g3 domain impaired glucose tolerance impaired fasting glucose acid-forming diet bristol myers squibb ilaria dicembrini comparator-controlled study present meta-analysis meta-analysis detected received consultancy fees conditions privacy policy check access instant access long-term comparison ppargamma-independent induction case-control study
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- Jadad AR, Moore RA, Carroll D et al (1996) Assessing the quality of reports of randomized clinical trials: is blinding necessary?
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headline:Thiazolidinediones and cancer: results of a meta-analysis of randomized clinical trials
description:Recent epidemiological data have contributed to the formulation of the hypothesis about the long-term safety of pioglitazone, a thiazolidinedione (TZD), with respect to malignancies, in particular bladder cancer. The primary aim of this meta-analysis of randomized clinical trials, not designed a priori to test this hypothesis, was to explore whether TZDs affect the risk of cancer. A meta-analysis was performed including published and unpublished randomized trials with a duration of at least 52 weeks, enrolling patients with or without diabetes, comparing TZDs with either placebo or other drug therapies on various different outcomes. We found 22 trials reporting at least one cancer and enrolling 13,197 patients to TZD (pioglitazone: n = 3,710 and rosiglitazone: n = 9,487) and 12,359 to placebo or active comparator groups. The mean follow-up was 26.1 months. Overall, those assigned at random to TZDs had a significant reduction (MH-OR 0.85 [0.73–0.98]; p = 0.027) in the incidence of malignancies, with no significant difference in effect between pioglitazone and rosiglitazone. Specifically, subgroup analyses showed a significant reduction for rosiglitazone (MH-OR 0.82 [0.69–0.98]; p = 0.029), but not for pioglitazone (MH-OR 0.66 [0.34–1.28]; p = 0.22). In further subgroup analyses of site-specific malignancies based on the data from four trials, the risk of bladder cancer with pioglitazone (MH-OR) was 2.05 [0.84–5.02]; p = 0.12. Further, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk of bowel cancer. In contrast, pioglitazone, but not rosiglitazone, was associated with a significant reduction in breast cancer. The present meta-analysis of trials, not designed a priori to test the hypothesis, provides reassuring evidence that TZDs are not associated with risk of overall malignancies. In fact, they are compatible with the possibility of a decreased risk of cancer. In site-specific subgroup analyses, for rosiglitazone, there was a significant decreased risk of bowel cancer. Subgroup analyses for pioglitazone did not allow to exclude an increased risk of bladder cancer, while the risk of breast cancer was significantly decreased. While these data are also useful to formulate not test hypotheses, they provide somewhat more cogent evidence than the previously published epidemiological data.
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