Study Examines Effect of Insulin With Metformin

Among patients with diabetes who were receiving metformin, the addition of insulin compared with a sulfonylurea, a class of antidiabetic drugs, was associated with an increased risk of nonfatal cardiovascular outcomes and all-cause death, according to a study in The Journal of the American Medical Association.

Diabetes and its complications represent an enormoushealth care burden and result in nearly 200,000 deaths annually. The American Diabetes Association and the European Association for the Study of Diabetesrecommend that for patients with preserved kidney function, diabetes treatment begins with metformin and lifestyle changes to achieve a glycated hemoglobin level of 7% or lower. Often patients will require a second agent to reach this goal, but there’s no consensus regarding which medication to choose, according to background information in the study.

Clinicians begin the administration of insulin to attain fast and flexible control of blood glucose levels. Because of the promisingresults of a few trials, there has been an increase in the early initiation of insulin and its use as add-on therapy to metformin.

Christianne L. Roumie, MD, MPH, of the VA-Tennessee Valley Healthcare System Geriatric Research Education Clinical Center and Vanderbilt University in Nashville, Tennessee, and colleagues conducted a study with data from the VA, 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 a sulfonylurea. The researchers compared the risk between therapies of a composite outcome 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 performed additional propensity-matched analysis on a subset of 2,436 patients from the insulin group and 12,180 patients from the sulfonylurea group. Patients had received metformin for a median of 14 months before adding another therapy; median follow-up after this addition was 14 months. An analysis of the subsequent events indicated that heart attack and stroke rates were statistically similar, whereas there was a higher rate of all-cause death among patients who received insulin.

“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 wrote. “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.”

Source: American Medical Association