OBJECTIVES: This study assesses the effect of glucose lowering drug (GLD) use, i.e. metformin, sulfonylurea derivatives (SUs), insulin and other GLDs, started after breast cancer diagnosis, on overall mortality. METHODS: All female breast cancer patients diagnosed between January 1^st, 1998 and December 31^st, 2011 who started using GLDs after breast cancer diagnosis, were included. Clinical characteristics were derived from the Netherlands Cancer Registry, drug dispensing data from the PHARMO Database Network and data on overall mortality from the Dutch municipal personal records database. Time-dependent Cox regression analysis, with cumulative exposure to GLDs were conducted to assess effects on overall mortality.

RESULTS: In total, 407 breast cancer patients were included. Most women (n=335, 82%) used metformin at some point during follow-up, followed by SUs (n=202, 50%), insulin (n=58, 14%) and other GLDs (n=41, 10%). The average follow-up was 7.7 ± 3.6 years and 107 (26%) patients died during follow-up. Adjusted analyses showed that metformin users had a lower overall mortality (HR=0.47; 95%CI:0.29-0.74), while insulin users had a higher overall mortality (HR=1.85; 95%CI:1.09-3.15) compared to non-users. However, when assessing dose-response effects no association was found between cumulative use of metformin, SU, insulin or other GLDs and mortality. CONCLUSIONS: GLDs were not associated with mortality among patients who started using GLDs after breast cancer diagnosis. We did observe a lower mortality among breast cancer patients using metformin and higher mortality among patients using insulin. However, as no dose-response relationship was observed, the found effects on mortality are likely to result from differences in patient characteristics that we could not adjust for and not from the drugs itself. Larger studies with longer follow-up among patients who start using GLDs after cancer diagnosis are needed to confirm our findings.