Metformin and Cancer Occurrence in Insulin-Treated Type 2's

In insulin-treated patients, the reduction of insulin doses determined by metformin could theoretically produce a decrease in cancer incidence. 

Metformin is associated with reduced cancer-related morbidity and mortality. The study was aimed at assessing the effect of metformin on cancer incidence in a consecutive series of insulin-treated patients.  

A nested case-control study was performed within a cohort of 1,340 patients, by sampling, for each case, age-, sex- and BMI-matched controls from the same cohort.  

During a median follow-up of 75.9 months, 112 cases of incident cancer were observed and compared with 370 controls. A significantly lower proportion of subjects was exposed to metformin and sulfanylureas among cases. After adjusting for comorbidity, glargine and total insulin doses, exposure to metformin, but not sulfonylureas, was associated with reduced incidence of cancer (OR 0.46[0.25-0.85],p=0.014, and 0.75[0.39-1.45],p=0.40, respectively).  

The present results confirm previous findings on the protective effect of metformin with respect to malignancies. Interestingly, this effect was evident even after adjusting for insulin doses, suggesting that the protective action of metformin cannot be entirely attributed to its insulin-sparing effects. Although insulin has mitogenic properties, and metformin reduces insulin requirements in Type 2 diabetic patients, the decrease in insulin doses determined by metformin does not explain the observed reduction of cancer incidence. This supports the notion of other mechanisms, independent of insulin dose. It is possible that patients not receiving metformin have a greater incidence of cancer due to comorbidities; the adjustment for a comorbidity score does not eliminate completely the possibility of a prescription bias. Conversely, the protective effect of sulfonylureas did not retain significance in multivariate analysis, suggesting that the higher proportion of sulfonylurea-treated patients among controls could be due either to lower comorbidity or to metformin co-treatment. The possibility of misdiagnosis of diabetes type in some cases should be considered.  

Current recommendations suggest the prosecution of metformin, unless contraindicated, in all insulin-treated Type 2 diabetic patients. This recommendation is motivated by the beneficial effects of metformin on insulin sensitivity, insulin doses, and glucose control. Beyond all those effects, the reduction of cancer risk could be a further, relevant reason for maintaining metformin in insulin-treated patients. 

Diabetes Care published online October 27, 2010