Higher dose of type 2 diabetes drug glyburide linked to cancer risk

By Joan Stephenson

NEW YORK (Reuters Health) - Longer use and higher doses of the sulfonylurea glyburide in patients with type 2 diabetes are associated with a significantly increased cancer risk, according to new research.

The findings, from a population-based cohort study by Canadian researchers, compared use of glyburide with that of other second-generation sulfonylureas.

"We observed duration- and dose-response relationships, which suggest that longer use as well as greater cumulative doses are associated with an increased risk of cancer," Dr. Laurent Azoulay, an oncologist at McGill University in Montreal, Quebec, told Reuters Health by email.

Previous research had linked glyburide use with an increased risk of cardiovascular conditions. The new findings suggesting a cancer-related risk "should help physicians better assess the risks and benefits of this drug," Dr. Azoulay said.

Several observational studies have associated sulfonylurea use, particularly glyburide, with an increased risk of cancer incidence and cancer-related mortality compared with other oral antidiabetic medications. But the few that specifically examined glyburide and cancer risk had a number of methodological limitations, Dr. Azoulay and colleagues note in Diabetes Care, online September 4.

"This is particularly important as there are some biological mechanisms that suggest that not all sulfonylureas may act the same way," the researcher said. Glyburide is the only sulfonylurea that appears to cause production of reactive oxygen species, a well-known cancer-promoting factor.

Using data from patient medical records in the U.K. Clinical Practice Research Datalink, Dr. Azoulay's team identified patients 40 years or older who were newly prescribed a second-generation sulfonylurea between 1988 and 2013.

Of the 52,600 patients in the cohort (mean age 64) followed for a mean of 5.3 years, more than 4,100 received a new diagnosis of cancer - an incidence of 14.6 per 1,000 person-years.

Glyburide use was associated with a nonsignificantly increased risk of any cancer compared with the use of other second-generation sulfonylureas (15.1 versus 14.6 per 1,000 person-years; hazard ratio, 1.09), the researchers found.

Repeating the primary analysis for breast, colorectal, lung, and prostate cancer, they found a nonsignificant increase in breast cancer (HR, 1.19) and a mild but significant protective effect (HR, 0.93) for lung cancer.

Secondary analyses revealed significant duration- and dose-response relationships between glyburide use and cancer risk.

Glyburide use for at least 36 months was associated with a significant increase in cancer risk (HR, 1.21), as was a cumulative dose of at least 1,096 defined daily doses (HR, 1.27).

Because of the growing prevalence of type 2 diabetes and the widespread use of glyburide, "the current findings raise concerns that need to be corroborated in other well-designed studies," the researchers said.

The study "provides additional evidence that there may be differences in the risks associated with the individual sulfonylureas, and that when studying these drugs, grouping them together as a class appears to be inappropriate," Dr. Kevin Pantalone of the Cleveland Clinic in Ohio, who was not involved in the study, told Reuters Health by email.

"The risk of hypoglycemia, and mortality (cardiovascular and/or overall) associated with the sulfonylureas seems to differ among the individual sulfonylureas, with glyburide being the most common (sulfonylurea) associated with these adverse risks," he noted.

The new findings, said Dr. Pantalone, "are additional evidence that we should no longer be using glyburide in routine clinical practice, given that other sulfonylureas are available at a similar cost and/or appear safer."

The study had no commercial funding. One author reported receiving consultation and speaker fees from six pharmaceutical companies.

SOURCE: http://bit.ly/1PZJPux

Diabetes Care 2015.

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