Association Of Metformin And Sulfonylureas With Cancer Risk In The Type2Diabetes Patients: A Meta-analysis

Introduction. Accumulating evidence suggests that patients with type2diabetesmellitus(T2DM) and hyperinsulinemia are at increased risk for developingmalignancies. It remains to be fully elucidated whether use of metformin, an insulinsensitizer, and/or sulfonylureas, insulin secretagogues, affect cancer incidence insubjects with T2DM.Material and Methods.We performed a meta-analysis using PubMed、CENTRAL、EMBASE、EBSCO、OVID、CBM, of randomized control trials (RCTs),cohorts, and case-control studies published through July2012that assess effects ofmetformin and/or sulfonylurea sulfonylureas on cancer risk at any site, in subjectswith T2DM. Fixed and random effects meta-analysis models were used, and theeffect size was summarized as relative risk (RR) for RCTs/cohorts and as odds ratio(OR) for the case-control studies.Results. Analysis of24metformin studies in subjects with T2DM showed thatmetformin use is associated with reduced risk for the development of cancer, in bothcohort (FE RR=0.70[95%CI=0.67-0.73];RE RR=0.86[95%CI=0.65-1.13]) andcase-control studies (OR=0.71[95%CI=0.57-0.88]), but this finding was notsupported by RCTs (RR=1.01[95%CI=0.81-1.26]). Data from18sulfonylureastudies in subjects with T2DM showed that sulfonylurea use is associated with anincrease in all cancer risk, in cohort studies (FE RR=1.55[95%CI=1.48-1.63]; RFRR=1.19[95%CI=0.88-1.62]), though data from RCTs (RR=1.17[95%CI=0.95-1.45])and case-control studies (OR=1.02[95%CI=0.93-1.13]) failed to demonstrate astatistically significant effect.Conclusions. This analysis using pooled primary data demonstrates thatmetformin use may be reduces, while sulfonylurea use may be associated with anincreased cancer risk in subjects with T2DM. These findings need to be confirmed inlarge-scale RCTs before they are translated into clinical practice.