Cancer Diagnosis Affects Adherence to Diabetes Drugs
Adherence to diabetes drugs falls after a diagnosis of cancer, a new study finds.
The results suggest that drop-offs in compliance with diabetes medication might negatively affect survival and could therefore partly explain the established higher cancer mortality seen among diabetes patients with worse glycemic control, say the authors, led by Dr Marjolein MJ Zanders (Netherlands Comprehensive Cancer Organization, Eindhoven).
The work, from a large Dutch database, was published onlineJanuary 28 in Diabetologia.
Dr Zanders told Medscape Medical News, “Both patients and medical professionals need to still pay attention to glucose-lowering drug use around a diagnosis of cancer. All medical specialists need to work with the patient for their overall health, and not just for one specific condition they are focused on.”
Overall, the researchers found a 6.3% decline in medication possession ratio (MPR) — a proxy for adherence — for glucose-lowering drugs among 3281 users of those agents at the time of subsequent cancer diagnosis compared with 12,891 users of diabetes medications who did not develop cancer. The “controls” were used to account for the drop-off in adherence typically seen among users of these medications.
The reasons for the decline in adherence can’t be gleaned from the data, but the authors offer several hypotheses.
Dr Zanders said one major unknown that should be examined in future studies is whether the drop-off is a result of “the patient who prioritizes the fight against cancer or the advice of the physician to stop the treatment.”
Effect Greater for Some Cancers Than Others
The study population included a total 52,228 patients from a pharmacy database in the southern Netherlands who were over 30 years of age (mean age, 68 years) and who had been dispensed glucose-lowering medications between 1998 and 2011.
Using data linked to a cancer registry, the authors matched up 3281 patients diagnosed with cancer during follow-up to four control patients each (total 12,891) for age, sex, duration of follow-up, type of glucose-lowering drug (including metformin, sulfonylureas, insulin, and others), and year of first dispensing. The follow-up time for the controls was matched to the time of cancer diagnosis in the cases.
The average time between the start of use of the glucose-lowering agent and the diagnosis of cancer (or matched date for the controls) was 3.7 years for both groups, and the total duration of follow-up was 6.6 years for cases and 6.5 for controls.
Before the cancer diagnosis, the MPR was increasing by about 0.1% per month. The 6.3% decline at the time of the cancer diagnosis compared with the controls translates to approximately 2 days per month attributable to cancer that the person isn’t using the glucose-lowering drug, the authors explain.
After the time of the cancer diagnosis, the MPR declined further by about 0.20% per month.
When specific cancers were examined, no declines in diabetes medication adherence were seen among patients diagnosed with prostate or breast cancer.
However, significant drop-offs in compliance that were greater compared with controls were seen among patients diagnosed with esophageal, stomach, pancreas, or liver cancers (12.5%) and pulmonary cancers (15.2%). Among those patients, subsequent further monthly drops in MPR were approximately 0.5% per month.
Declines in medication adherence also rose with more advanced cancer, with an MPR drop of 10.7% at the time of diagnosis of stage IV disease, declining an additional 0.64% per month thereafter.
“The largest drops in medication possession ratio at the time of cancer diagnosis, in the range of 11% to 15%, were seen among patients with stage IV disease and gastrointestinal or pulmonary cancers,” the authors note.
And the impact of a cancer diagnosis on adherence was strongest among patients using sulfonylureas in combination with metformin for glucose lowering and in those using insulin, alone or in combination.
What’s Behind the Adherence Slide?
The authors note that an MPR of more than 80% is considered adherent, so the declines of less than 20% seen here may or may not be considered clinically important. However, they add, studies have suggested that even a small change in MPR can impair glycemic control.
The finding of no impact on adherence from a diagnosis of breast cancer contrasts with a previous study that found a decline in MPR from 85% to 49% among breast-cancer patients, but that study did not include a control group.
In one previous study of diabetes patients (without cancer) with treatment durations less than 10 years, approximately two-thirds had an MPR less than 65%, Dr Zanders and colleagues point out.
The finding of a greater drop in adherence with higher tumor stage suggests that users of diabetes medications “might prioritize the fight against cancer over the effort required to have a good metabolic control for their diabetes,” they suggest.
On the other hand, prognosis may only partially explain the effect, since the diagnosis of esophageal cancer reduced adherence more than did that of pancreatic cancer, even though 3-year survival rates are 17% for esophageal compared with just 6% for pancreatic cancer.
The difference might alternatively be explained by worse cancer symptoms, the authors speculate.
“In future studies, the reason for the decline in medication adherence needs to be further elucidated among the different cancer types,” Dr Zanders noted.
For now, she said, the message is: “Diabetes and cancer treatments have different goals, but these goals should be able to go along together.”
Diabetologia. Published online January 28, 2015.