Association between metformin use and mortality after cervical cancer in older women with diabetes

Background — To examine the association between metformin use and mortality in patients with diabetes and cervical cancer.

Methods — Using Ontario health databases, a retrospective, population-based cohort study was conducted in women with diabetes ≥ age 66 diagnosed with cervical cancer between 1997-2010. The association between metformin exposure and cervical cancer-specific mortality was examined using Fine-Gray regression models, with non-cancer death as a competing risk and cumulative metformin use as a time-varying exposure. The association with overall mortality was examined using Cox regression models.

Results — Among the 181 women with diabetes and cervical cancer, there were 129 deaths, including 61 cervical cancer-specific deaths. The median follow-up was 5.8 years (interquartile range 4.2-9.6 years) for surviving patients. Cumulative dose of metformin after cervical cancer diagnosis was independently associated with a decreased risk of cervical cancer-specific mortality and overall mortality in a dose-dependent fashion (HR 0.79, 95% CI 0.63-0.98; and HR 0.95, 95% CI 0.90-0.996 per each additional 365g of metformin use, respectively). There was no significant association between cumulative use of other anti-diabetic drugs and cervical cancer-specific mortality.

Conclusion — This study suggests an association between cumulative metformin use after cervical cancer diagnosis and lower cervical cancer-specific and overall mortality among older women with diabetes.

Impact — Cumulative dose of metformin use after cervical cancer diagnosis among older women with diabetes may be associated with a significant decrease in mortality. This finding has important implications if validated prospectively, as metformin is inexpensive and can be easily combined with standard treatment for cervical cancer.