Diabetes, metformin use, and colorectal cancer survival in women: A retrospective cohort study.

Abstract

e14005 Background: Observational studies have associated metformin use with lower colorectal cancer incidence but few studies have examined survival impact. We examined the relationship between metformin use, diabetes, and survival in postmenopausal women diagnosed with colorectal cancer while participating in the Women’s Health Initiative (WHI) Clinical Trial or Observational Study. Methods: 2,066 postmenopausal women with colorectal cancer diagnosed while enrolled in the WHI were followed for a median of 4.1 years, with 589 deaths overall and 414 colorectal cancer deaths. In this cohort, overall and colorectal cancer-specific survival were compared among women with diabetes who reported ever using metformin (n=84); those with no reported use of metformin (n=128); and women without diabetes (n=1854). Cox proportional hazard models were used to estimate the associations between metformin use, diabetes and survival outcomes from the time of colorectal cancer diagnosis. Two strategies were used to adjust for potential confounders: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage at diagnosis, women with diabetes on metformin had no significant difference in colorectal-cancer specific survival compared to metformin non-users (HR 0.75; 95% CI 0.40 -1.38, p=0.67) or compared to women without diabetes (HR 1.00; 95% CI 0.61 - 1.66, p=0.99). With propensity score adjustment, the HR for colorectal cancer-specific survival in women with diabetes on metformin compared to non-users was 0.90 (95% CI 0.48 – 1.69, p=0.75). Women with diabetes reporting metformin use had no significant difference in overall survival compared to non-users (HR 0.84; 95% CI 0.51 – 1.37; p=0.48) or non-diabetics (HR 1.20; 95% CI 0.80 - 1.79; p=0.39). Conclusions: In postmenopausal women with colorectal cancer and diabetes, no statistically significant difference was seen in colon-cancer specific survival in those who used metformin. Analyses in larger populations of colorectal cancer patients are warranted.