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2014 ; 7
(9
): 867-85
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Metformin and cancer risk and mortality: a systematic review and meta-analysis
taking into account biases and confounders
#MMPMID24985407
Gandini S
; Puntoni M
; Heckman-Stoddard BM
; Dunn BK
; Ford L
; DeCensi A
; Szabo E
Cancer Prev Res (Phila)
2014[Sep]; 7
(9
): 867-85
PMID24985407
show ga
Previous meta-analyses have shown that the antidiabetic agent metformin is
associated with reduced cancer incidence and mortality. However, this effect has
not been consistently demonstrated in animal models and recent epidemiologic
studies. We performed a meta-analysis with a focus on confounders and biases,
including body mass index (BMI), study type, and time-related biases. We
identified 71 articles published between January 1, 1966, and May 31, 2013,
through Pubmed, ISI Web of Science (Science Citation Index Expanded), Embase, and
the Cochrane library that were related to metformin and cancer incidence or
mortality. Study characteristics and outcomes were abstracted for each study that
met inclusion criteria. We included estimates from 47 independent studies and
65,540 cancer cases in patients with diabetes. Overall cancer incidence was
reduced by 31% [summary relative risk (SRR), 0.69; 95% confidence interval (CI),
0.52-0.90], although between-study heterogeneity was considerable (I(2) = 88%).
Cancer mortality was reduced by 34% (SRR, 0.66; 95% CI, 0.54-0.81; I(2) = 21%).
BMI-adjusted studies and studies without time-related biases also showed
significant reduction in cancer incidence (SRR, 0.82; 95% CI, 0.70-0.96 with I(2)
= 76% and SRR, 0.90; 95% CI, 0.89-0.91 with I(2) = 56%, respectively), albeit
with lesser magnitude (18% and 10% reduction, respectively). However, studies of
cancer mortality and individual organ sites did not consistently show significant
reductions across all types of analyses. Although these associations may not be
causal, our results show that metformin may reduce cancer incidence and mortality
in patients with diabetes However, the reduction seems to be of modest magnitude
and not affecting all populations equally. Clinical trials are needed to
determine if these observations apply to nondiabetic populations and to specific
organ sites.