Insulin added to metformin for T2DM associated with increased risk of death

Patients with type 2 diabetes mellitus who received metformin and then added insulin were at higher risk of all-cause mortality than those who added a sulfonylurea, according to a report published June 11 in JAMA.

Christianne L. Roumie, MD, MPH, of the Veterans Health Administration-Tennessee Healthcare System Geriatric Research Education Clinical Center, Nashville, Tenn., and her colleagues undertook a retrospective study of veterans who were treated initially with metformin in 2001 through 2008 and then were treated with the addition of insulin or sulfonylurea to achieve glycemic control. Patients were followed to compare time to acute myocardial infarction, stroke, or death.

Approximately 178,000 diabetes patients were treated with metformin and then almost 3,000 decided to add insulin to their therapy and nearly 40,000 chose a sulfonylurea for glycemic control. At the time of the second-line medication being started, patients had been treated with metformin for a median of 14 months. Their median hemoglobin A1c level was 8.1%. After therapy intensification, the median follow-up was 14 months.

“Acute myocardial infarction and stroke rates were statistically similar, 41 vs. 229 events (10.2 and 11.9 events per 1000 person-years)…, whereas all-cause death rates were 137 vs. 444 events, respectively (33.7 and 22.7 events per 1000 person-years),” Roumie and her colleagues reported.

“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.”

The authors suggest more study is need to understand these risks of using insulin in patients on metformin monotherapy who need better glycemic control.