Cancer Risk in Diabetic Patients Treated with Metformin: A Systematic Review and Meta-analysis

Abstract

BackgroundA growing body of evidence has suggested that metformin potentially reduces the risk of cancer. Our objective was to enhance the precision of estimates of the effect of metformin on the risk of any-site and site-specific cancers in patients with diabetes.Methods/Principal FindingsWe performed a search of MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for pertinent articles published as of October 12, 2011, and included them in a systematic review and meta-analysis. We calculated pooled risk ratios (RRs) for overall cancer mortality and cancer incidence. Of the 21,195 diabetic patients reported in 6 studies (4 cohort studies, 2 RCTs), 991 (4.5%) cases of death from cancer were reported. A total of 11,117 (5.3%) cases of incident cancer at any site were reported among 210,892 patients in 10 studies (2 RCTs, 6 cohort studies, 2 case-control studies). The risks of cancer among metformin users were significantly lower than those among non-metformin users: the pooled RRs (95% confidence interval) were 0.66 (0.49–0.88) for cancer mortality, 0.67 (0.53–0.85) for all-cancer incidence, 0.68 (0.53–0.88) for colorectal cancer (n = 6), 0.20 (0.07–0.59) for hepatocellular cancer (n = 4), 0.67 (0.45–0.99) for lung cancer (n = 3).Conclusion/SignificanceThe use of metformin in diabetic patients was associated with significantly lower risks of cancer mortality and incidence. However, this analysis is mainly based on observational studies and our findings underscore the more need for long-term RCTs to confirm this potential benefit for individuals with diabetes.

Thyroid cancer metabolism: A review

“…Extensive preclinical data supports the efficacy of metformin as an antineoplastic agent [67], inhibiting cancer cell proliferation in gastric, medullary thyroid, breast, and pancreatic cancers [68][69][70][71]. Epidemiologic studies have also shown a decreased risk of cancer incidence and mortality from metformin use in diabetics [72], and clinical trials elucidating metformin's effect on head and neck squamous cell carcinoma are already underway. Further studies assessing its role in thyroid cancer, among other cancers, are needed to support these claims.…”

Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis

“…However, other studies did not detect the relationship between metformin treatment and CRC risk among diabetes (Yang et al 2004;Bodmer et al 2012;Cardel et al 2014;Tsilidis et al 2014;Xu et al 2014). Several meta-analyses were conducted to evaluate the relationship, while the tissue still remains controversial (Decensi et al 2010;Zhang et al 2011;Noto et al 2012;Soranna et al 2012;Gandini et al 2014). …”

Development and validation of fast and simple flow injection analysis–tandem mass spectrometry (FIA–MS/MS) for the determination of metformin in dog serum

“…Of recent interest is the potential repurposing of metformin, an oral insulinsensitizer used as first-line treatment for Type 2 diabetes (DM2). Specifically, there is now interest in validating the several meta-analyses indicating the usefulness of metformin in cancer therapy and/or prevention [1][2][3]. Indeed, cytotoxic effects of metformin in many cancer cell lines has been demonstrated [4,5].…”