How Does Medication Adherence Affect Mortality Risk in Patients With Colorectal Cancer, Diabetes?

For individuals with both diabetes and colorectal cancer, high adherence to oral diabetes medication was associated with a significantly reduced risk of overall mortality compared with lower adherence, according to a study published in Cancer Epidemiology, Biomarkers & Prevention.

In 2018, colorectal cancer ranked second globally in terms of mortality and third in terms of incidence of all cancers, while the global prevalence of diabetes was estimated at 8.5% in 2014. In addition, the authors note there is an increased risk for long-term, all-cause mortality among patients with colorectal cancer and preexisting diabetes.

According to the researchers, “Diabetes mellitus is known to have a negative effect on colorectal cancer survival due to hyperinsulinemia or hyperglycemia, and medications such as metformin, which targets insulin resistance and hyperinsulinemia, have a preventive effect on the risk of death.”

Despite increasing rates of diabetes in recent years, one report found medication adherence among those diagnosed was only around 60%.

To compare the risk of death among patients with colorectal cancer and diabetes who had different adherence levels to oral antidiabetics, the investigators compiled data from 33,841 patients with diabetes and newly diagnosed colorectal cancer between 2002 and 2016 in South Korea.

In this retrospective cohort study, patients were followed-up with from the date of diagnosis until death or December 2016, for an average follow-up period of 4.7 years. Medication adherence was calculated as the proportion of days covered (PDC), while HR and 95% CI for death were estimated using low-adherence patients as references. Specifically, PDC were calculated as “the number of days with drug on hand divided by the number of days in the specified time interval.”

Of the patients included in the study, 7615 (PDC ≥ 80%) were found to be adherent and 26,226 (PDC < 80%) nonadherent with oral diabetes medications. Overall, less than 23% of patients included were highly adherent to their oral medications.

“Patients with colorectal cancer with good adherence showed a reduced risk of death (HR, 0.82; 95% CI, 0.78-0.86) compared with those with poor adherence…In our crude and adjusted models, maintaining good adherence to medication showed a 16% to 19% lowered risk of death," the researchers said.

Data revealed the mean age at diagnosis of colorectal cancer was higher in adherent patients, while the proportion of insulin and metformin ever-users was higher in nonadherent patients.

During the time frame, there were 1958 and 8076 deaths among the adherent and nonadherent individuals, respectively. Stratified analyses for cancer subsites also revealed a lower risk of death for every cancer subsite. Notably, patients with distal colon cancer exhibited a 21% to 24% reduced risk.

One potential explanation for why oral antidiabetics may enhance survival among patients with colorectal cancer is because “these medications are mainly focused on improving hyperglycemia or hyperinsulinemia," the authors said. These conditions "are the acknowledged mechanisms by which diabetes mellitus contributes to cancer progression, the better the adherence, the stronger the effect of improving the survival of patients with cancer."

Reference

Choe S, Lee J, Park JW, et al. Prognosis of patients with colorectal cancer with diabetes according to medication adherence: a population-based cohort study. Cancer Epidemiol Biomarkers Prev. Published online June 1, 2020. doi:10.1158/1055-9965.EPI-19-1455