Mortality Rises as Sulfonylurea Dose Increases

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Mortality Rises as Sulfonylurea Dose Increases

http://www.medscape.com/viewarticle/521964

NEW YORK (Reuters Health) Jan 20 - The findings from a new study by

researchers in Canada lend further support to the controversial belief

that sulfonylurea drugs increase mortality in patients with diabetes.

A 1970 report suggested there is a link between sulfonylurea use and

cardiovascular events. Since then other study findings have refuted this

association, and sulfonylureas have remained a mainstay of diabetes therapy.

In previous studies, Dr. Scot H. Simpson and colleagues, from the

University of Alberta in Edmonton, Canada, had shown that metformin

offers a survival advantage over the sulfonylureas. Still, it was

unclear if this was due to a protective effect of metformin or from a

potentially adverse effect from the sulfonylureas.

To investigate, Dr. Simpson's team analyzed data for 5795 subjects who

were prescribed a first-ever oral antidiabetic agent and were entered in

the Saskatchewan Health databases between 1991 and1999. The main

objective was to determine if a dose-response relation existed between

sulfonylurea use and mortality.

The researchers' findings appear in the Canadian Medical Association

Journal for January 17th.

The patients were an average of 66.3 years of age, 43.4% were female,

and they were followed for a mean of 4.6 years. The antidiabetic agents

used included first-generation sulfonylureas for 120 subjects, glyburide

for 4138, and metformin for 1537.

At higher daily doses sulfonylurea and, to a lesser extent, glyburide

were associated with an increased risk of death, whereas a dose-response

relationship was not seen with metformin.

" This evidence, taken within the context of observations collected over

the last 30 years, suggests that clinicians should carefully assess the

need for sulfonylurea therapy in subjects at high risk of cardiovascular

events -- particularly now, when several other classes of antidiabetic

oral medications are available, " the investigators conclude.

In a related commentary, Dr. S. H. Bell, from the University of

Alabama at Birmingham, notes that sulfonylureas may raise the risk of

death by directly affecting the myocardium. Even though these agents are

still a popular treatment for diabetes, he believes that they should be

relegated to third-line therapy, which is consistent with recently

published guidelines.

CMAJ 2006;174:169-174,185-186.

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