Metformin and statins not linked to ovarian cancer in women with type 2 diabetes

There is no evidence that metformin or statins reduce the incidence of ovarian cancer in women with type 2 diabetes (T2D), according to a study published in BJOG: An International Journal of Obstetrics and Gynaecology.

It has been reported that compared to non-diabetics, people with T2D have an increased incidence of various cancers, including ovarian cancer; however, other studies found no association.

Metformin has anti-mitotic, anti-angiogenic, and anti-inflammatory properties. Some epidemiological studies have linked metformin use with reduced incidence of ovarian cancer and other types of cancer.

It is also thought that statins have the potential to prevent cancer, due in part to the mechanism that blocks the formation of cholesterol.

This retrospective cohort study, led by Elina Urpilainen, of the University of Oulu in Finland, used national registries in Finland to identify women over 40 years of age diagnosed with T2D to evaluate the role of antidiabetic medications and statins on the incidence of epithelial ovarian cancer.

The study utilized the FinDM database, which contains information from several registries, including diagnosis of diabetes and cancer, as well as accurate information regarding types of medication used and dates purchased.

The database identified women diagnosed with T2D from 1996 to 2011; entry to follow-up was the 40th birthday or one year after diagnosis of T2D, to reduce risk of detection and reverse causality bias. The final cohort consisted of 137,643 women.

In addition, a nested case-control study within the cohort evaluated the association of ovarian cancer with cumulative medication use. For each case, up to 20 controls were selected and matched for age and duration of diabetes.

Antidiabetic medication was evaluated in three separate categories: metformin, other oral antidiabetic medication, and insulin. Statins were assessed as one category. The effects of cumulative use of medication was assessed using the total amount of defined daily doses (DDD) purchased during the follow-up period.

The follow-up included a total of 748,282 person-years at risk, and the mean follow-up time was 5.4 years. During the study period, 303 women were diagnosed with epithelial ovarian cancer. The incidence was highest in the 60 to 69 year age-group (51.4 per 100,000 person-years), and in women with a duration of diabetes of 5 to 8 years (52.2 per 100,000 person-years).

In the nested case-control analysis, there were 6,060 matched controls. Most (66%) were metformin users. The most common other oral antidiabetic medication was sulfonylurea. More than half (52.5%) were ever-users of statins. Simvastatin was used most frequently.

In the full cohort, incidence of ovarian cancer was not associated with ever-use of metformin, insulin, or statins (adjusted hazard ratio [HR] 1.02, 1.19, and 0.99, respectively).

The investigators did not observe a consistent trend by time since onset of T2D; they did not have sufficient evidence for any interaction between duration of T2D and any of the medications evaluated.

The results were similar in the case-control analysis. Incidence of ovarian cancer and ever-use of metformin, insulin, or statins was not associated with ovarian cancer (adjusted HRs of 0.91, 1.19, and 0.96, respectively).

Moreover, there was no evidence of an interaction effect of ever-use of statins and metformin. In terms of DDD, there was also no consistent trend in the incidence of ovarian cancer with respect to cumulative use of metformin, other antidiabetic medication, insulin, or statins.

The researchers acknowledge that the study could be limited by the lack of information regarding family history and parity the women in the cohort. In addition, they did not have access to data such as BMI or markers of insulin resistance. Only prescribed medications reimbursed by the national health insurance system were included; medications dispensed in hospitals and outpatient clinics were not captured.

“We found no evidence for an association between the use of metformin or other forms of oral antidiabetic medication and the incidence of epithelial ovarian cancer in women with T2D,” concluded the authors.

In addition, they did not find any association between statin use and the risk of epithelial ovarian cancer.

To read more about this study, click here.