Insulin's risks as second-line medicine to treat type 2 diabetes

New heart attacks and strokes occurred at similar rates in both groups but death (from all causes) was 44 percent higher in patients who added insulin compared to those who added a sulfonylurea.

The study appeared this week in the Journal of the American Medical Association (JAMA), highlighted with an accompanying editorial and an online video interview with lead author Christianne Roumie, M.D., MPH, associate professor of Medicine and Pediatrics.

Roumie and colleagues compared medical records of two groups of Veterans Health Administration patients with diabetes: 2,436 who took metformin and insulin, and 12,180 who instead took metformin and one or another type of sulfonylurea. The research team accounted for patient co-morbidities, age, duration of treatment, smoking status, sex, race and physiologic variables, including diabetes control.

Some 26 million Americans have diabetes (type 2 accounts for between 90 and 95 percent of all diabetes in the United States). Diet and exercise often provide an effective first-line intervention for this disease, but many patients require a medication, and metformin is recommended as a first-line treatment. Many patients eventually require additional medicines, and according to Roumie the choice of a second medication has been less clear.

"A couple of small clinical trials have shown that using insulin earlier in a disease course helps preserve beta cells in your pancreas longer," she said. On the other hand, "multiple large clinical trials have found either no benefit or potential harm from attempting very tight management of glucose. We wanted to look within a real-world practice at the drugs that patients use and evaluate the outcomes."

In a statement accompanying the study, Roumie wrote, "Although adding insulin seems a reasonable option for some patients who have very high glucose or who desire flexible and fast blood sugar control, the study findings suggest that for most patients who need a second diabetes drug, adding a sulfonylurea to metformin should be preferred to adding insulin."

At present, any underlying mechanism that might explain the increased risk of death found in the study remains unknown. Roumie and colleagues have a number of studies planned to examine possible mechanisms, and are now investigating type 2 diabetes outcomes associated with blood glucose swings and with episodes of hypoglycemia (low blood sugar) tied with insulin use.

Roumie was joined in the study by Vanderbilt investigators Robert Greevy, Ph.D.; Carlos Grijalva, M.D., MPH; Adriana Hung, M.D., MPH; Xulei Liu, M.D., MS; Harvey Murff, M.D., MPH; Tom Elasy, M.D., MPH; and Marie Griffin, M.D., MPH.

The study was performed under the aegis of Vanderbilt's DEcIDE Center (Developing Evidence to Inform Decisions about Effectiveness), and was supported by the Agency for Healthcare Research and Quality, the National Institutes of Health (grant DK092986) and the Department of Veterans Affairs.