Combo of diabetes drugs may increase mortality

By David Douglas

NEW YORK (Reuters Health) - Combination treatment for type 2 diabetes using two classes of drugs -- metformin and sulfonylureas -- may increase the risk of hospitalization for cardiovascular disease and mortality, according to a report in the current issue of Diabetes Care.

Researchers came to this conclusion after an analysis of pooled data from nine large observational studies.

"The paper highlights a real dilemma we have today in diabetes treatment," senior investigator Dr. Vivian A. Fonseca told Reuters Health. "We have drugs that lower glucose but we seem to run into problems over time with improving outcomes -- particularly cardiovascular outcomes."

"A big question," he added, "is whether it is due to the disease or the drugs increasing cardiovascular risk."

To help answer that question, Fonseca of Tulane University School of Medicine, New Orleans, and colleagues performed a review of data from more than 101,000 study participants, about one quarter of whom received combination therapy with metformin and sulfonylurea. The other patients were treated with one of these agents or diet therapy.

In the combination group, the risk of mortality from any cause was increased by 19 percent and by 29 percent for cardiovascular mortality. There were no statistically significant differences, however, when compared with the mortality rates in the other groups.

However, the combined end-point of death or hospitalization due to cardiovascular disease was increased by 43 percent in the group on combination therapy, which was significantly greater than in the other groups.

"So it appears," continued Fonseca, "that there is some increased risk with this combination that is the most widely used diabetes treatment of two drugs that are cheap and generic."

Our findings, he concluded, "clearly demonstrate that further studies are needed not only to assess the association of combination therapy of metformin and sulfonylurea with all-cause and/or cardiovascular mortality, but also to understand the potential underlying mechanism of its effects."

SOURCE: Diabetes Care, August 2008.