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July 2, 2014
Sulfonylurea Preferable to Insulin As Diabetes
Therapy Add-On

Nashville—Despite the increased push for early initiation of insulin in patients with type 2 diabetes, a new study suggests that might not always be a good idea.

Among patients with diabetes who were receiving metformin, the addition of insulin compared with a sulfonylurea was associated with an increased risk of nonfatal cardiovascular outcomes and all-cause death, according to researchers from the Veterans Health Administration-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center, and Vanderbilt University, both in Nashville. Their report was published recently in the Journal of the American Medical Association.

Guidelines from the American Diabetes Association and the European Association for the Study of Diabetes recommend that for patients with preserved kidney function, diabetes treatment begin with metformin and lifestyle changes to achieve a glycated hemoglobin (HbA1c) level of less than or equal to 7%. While a second agent often is required for patients to reach the goal, no consensus has been reached of which therapy to choose, according to background in the study.

Because a few trials have shown that insulin can offer fast and flexible control of blood glucose level, early initiation of insulin as well as its use as add-on therapy to metformin has been widely promoted, according to the report.

For the study, researchers reviewed data from national Veterans Health Administration, Medicare, and National Death Index databases, which included veterans with diabetes initially treated with metformin from 2001 through 2008 who subsequently added either insulin or sulfonylurea. The therapies were compared for risk of heart attack, stroke, or all-cause death.

Among 178,341 metformin monotherapy patients, 2,948 added insulin and 39,990 added a sulfonylurea. The authors analyzed a propensity matched subset of 2,436 patients from the insulin group and 12,180 patients from the sulfonylurea group to find that heart attack and stroke rates were statistically similar, but the rate of all-cause death among patients who received insulin was higher. Patients had received metformin for a median of 14 months before adding another therapy and were followed for another 14 months.

“Our finding of a modestly increased risk of a composite of cardiovascular events and death in metformin users who add insulin compared with sulfonylurea is consistent with the available clinical trial and observational data. None of these studies found an advantage of insulin compared with oral agents for cardiovascular risk, and several reported increased cardiovascular risk or weight gain and hypoglycemic episodes, which could result in poorer outcomes,” the authors write. “Our study suggests that intensification of metformin with insulin among patients who could add a sulfonylurea offers no advantage in regard to risk of cardiovascular events and is associated with some risk.”

“These findings require further investigation to understand risks associated with insulin use in these patients and call into question recommendations that insulin is equivalent to sulfonylureas for patients who may be able to receive an oral agent.”

In an accompanying editorial, Monika M. Safford, MD, of the University of Alabama at Birmingham, said the nature of the study—comparative effectiveness research—can “create barriers to interpretation that may make it more difficult to apply their results. Some of the creativity being brought to bear on advancing methods of analysis may also be needed to advance methods of communicating both methods and results to practicing clinicians, and perhaps more importantly, to the patients who are facing decisions that may (or may not) have profound implications for their health and well-being.”



U.S. Pharmacist Social Connect