Metformin use and cervical cancer risk in female patients with type 2 diabetes

This study evaluated whether metformin may affect the risk of cervical cancer. The reimbursement databases of the Taiwan's National Health Insurance were used. Female patients with type 2 diabetes at an onset age of 25-74 years during 1999-2005 and newly treated with metformin (n=132971, "ever users of metformin") or other antidiabetic drugs (n=6940, "never users of metformin") were followed for at least 6 months until December 31, 2011. The treatment effect of metformin (for ever versus never users, and for tertiles of cumulative duration of therapy) was estimated by Cox regression incorporated with the inverse probability of treatment weighting using propensity score. Analyses were also conducted in a 1: 1 matched pair cohort based on 8 digits of propensity score. Results showed that the respective numbers of incident cervical cancer in ever users and never users were 438 (0.33%) and 38 (0.55%), with respective incidences of 68.29 and 121.38 per 100,000 person-years. The overall hazard ratio suggested a significantly lower risk in metformin users (0.558, 95% confidence intervals: 0.401-0.778). In tertile analyses, the hazard ratios (95% confidence intervals) for the first (< 23.0 months), second (23.0-47.9 months) and third (> 47.9 months) tertile of cumulative duration were 1.272 (0.904-1.790), 0.523 (0.366-0.747) and 0.109 (0.070-0.172), respectively. Findings were supported by the analyses in the matched cohort. In conclusion, metformin may significantly reduce the risk of cervical cancer, especially when the cumulative duration is more than 2 years.