Metformina en obesidad, cáncer y envejecimiento: abordando las controversias
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Metformin in obesity, cancer and aging: addressing controversies.
Berstein LM.
Source
Laboratory of Oncoendocrinology, N.N.Petrov Research Institute of Oncology, St. Petersburg, Russia. levmb@endocrin.spb.ru
Aging (Albany NY). 2012 May;4(5):320-9.
Abstract
Metformin, an oral anti-diabetic drug, is being considered increasingly for treatment and prevention of cancer, obesity as well as for the extension of healthy lifespan. Gradually accumulating discrepancies about its effect on cancer and obesity can be explained by the shortage of randomized clinical trials, differences between control groups (reference points), gender- and age-associated effects and pharmacogenetic factors. Studies of the potential antiaging effects of antidiabetic biguanides, such as metformin, are still experimental for obvious reasons and their results are currently ambiguous. Here we discuss whether the discrepancies in different studies are merely methodological or inherently related to individual differences in responsiveness to the drug.
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| Terapia con metformina y riesgo de cáncer en diabéticos tipo 2. Revisión sistemática |
Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review.
Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A.
Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, S. Maria Imbaro (CH), Chieti, Italy.
PLoS One. 2013 Aug 2;8(8):e71583. doi: 10.1371/journal.pone.0071583. Print 2013.
Abstract
AIMS/HYPOTHESIS:Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes. METHODS: DATA SOURCE: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers. RESULTS:Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma. CONCLUSIONS/INTERPRETATION: Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
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| Riesgo de cáncer asociado con el uso de metformina y sulfonilurea en diabetes tipo 2: un meta-análisis |
Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis.
Soranna D, Scotti L, Zambon A, Bosetti C, Grassi G, Catapano A, La Vecchia C, Mancia G, Corrao G.
Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche Mario Negri, Via La Masa 19, Milan, Italy.
Oncologist. 2012;17(6):813-22. doi: 10.1634/theoncologist.2011-0462. Epub 2012 May 29.
Abstract
OBJECTIVE: Oral antidiabetic drugs (including metformin and sulfonylurea) may play a role in the relationship between type 2 diabetes and cancer. To quantify the association between metformin and sulfonylurea and the risk of cancer, we performed a meta-analysis of available studies on the issue. MATERIALS AND METHODS: We performed a MEDLINE search for observational studies that investigated the risk of all cancers and specific cancersites in relation to use of metformin and/or sulfonylurea among patients with type 2 diabetes mellitus. Fixed- and random-effect models were fitted to estimate the summary relative risk (RR). Between-study heterogeneity was tested using χ(2) statistics and measured with the I(2) statistic. Publication bias was evaluated using funnel plot and Egger's regression asymmetry test. RESULTS: Seventeen studies satisfying inclusion criteria and including 37,632 cancers were evaluated after reviewing 401 citations. Use of metforminwas associated with significantly decreased RR of all cancers (summary RR 0.61, 95% confidence interval [CI] 0.54-0.70), colorectal cancer (0.64, 95% CI 0.54-0.76), and pancreatic cancer (0.38, 95% CI 0.14-0.91). With the exception of colorectal cancer, significant between-study heterogeneity was observed. Evidence of publication bias for metformin-cancer association was also observed. There was no evidence that metformin affects the risk of breast and prostate cancers, nor that sulfonylurea affects the risk of cancer at any site. CONCLUSIONS: Metformin, but not sulfonylurea, appears to reduce subsequent cancer risk. This has relevant implications in light of the exploding global epidemic of diabetes.
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