Diabetic Pharmacotherapy and Endometrial Cancer Risk Within a Publicly Funded Health Care System

There is conflicting evidence regarding the association between metformin and endometrial cancer risk. The objective of this study was to evaluate the association between type of diabetic pharmacotherapy and endometrial cancer risk within a population-based study. The hypothesis was that metformin was associated with the lowest risk.

This was a nested case-control study using data from the BC Cancer Registry (2000-2009) and from a province-wide prescription network (PharmaNet) since 1996. Patients were classified by drug exposure (metformin, thiazolidinediones, secretagogues, with or without insulin). The primary analysis was a conditional logistic regression to estimate the odds ratios for endometrial cancer in the drug exposure groups. Sensitivity analysis was carried out to account for uncertainty regarding various parameters. The secondary analysis evaluated the effect of dosage using a principal components analysis.

The study cohort comprised 492 cases and 4404 controls. The primary analysis revealed no difference in endometrial cancer risk between those using metformin and those prescribed other classes of medications (OR 1.5, 95% CI 0.9 to 2.4). Women receiving all classes of medications had almost a two-fold increase in risk (OR 1.9, 95% CI 1.1 to 3.3). The secondary analysis revealed an increased risk associated with a greater duration of treatment and number of prescriptions (OR 1.3, 95% CI 1.2 to 1.4).

In this population-based study, metformin was not associated with a decreased endometrial cancer risk. Women receiving multiple types of medications over a long time had the highest risk, implying that the extent of insulin resistance, rather than the effect of any specific medication, drives endometrial cancer risk.