ADA: Antidepressants Raise Diabetes Risk

WASHINGTON, June 11 ? Antidepressants may exacerbate the risk of developing type 2 diabetes in those with impaired glucose tolerance, researchers reported here.

Although it's still unclear whether depression itself raises the risk of type 2 diabetes, as some have suggested, patients in the Diabetes Prevention Program who took antidepressants had double or triple the likelihood of developing type 2 diabetes, Richard R. Rubin, Ph.D., of Johns Hopkins, and colleagues, reported at the American Diabetes Association Meeting here.

The Diabetes Prevention Program (DPP) was a three-year, 27-center placebo-controlled study of 3,234 participants who were overweight and had impaired glucose tolerance (IGT). The results, published in the Feb. 7, 2002, issue of the New England Journal of Medicine, showed that diet and exercise could, to a large degree, prevent or delay the onset of type 2 diabetes, and that the use of Glucophage (metformin) could also contribute to delaying the onset.

In the current subanalysis, the investigators found that those who reported taking an antidepressant at randomization and who were assigned to the intensive lifestyle modification or placebo arms?but not to the Glucophage arm?had a two- to three-fold greater risk of developing type 2 diabetes.

The authors also found, however, that people with elevated depressive symptoms on the Beck Depression Inventory who were not taking antidepressants at study entry had no increased risk for type 2 diabetes, said Dr. Rubin and colleagues.

The finding of an antidepressant-diabetes link has "some fairly profound public health implications, in that according to estimates there are about 40 million Americans who have pre-diabetes?people with impaired glucose tolerance," Dr. Rubin said at a briefing.

"In addition, antidepressant medication use is increasing dramatically around the country and probably conservatively 10% to 15% of Americans are taking antidepressant medication, so these findings potentially apply to very large numbers of citizens in our country."

The investigators had previously reported that in the entire study population, baseline Beck Depression Inventory scores predicted risk of developing diabetes in the intensive lifestyle arm, but not in the Glucophage or placebo arms, after controlling for age, gender, race/ethnicity, education. Additionally, when they controlled for weight change in patients in the intensive lifestyle arm, the association with depression was no longer significant.

In the current study, they hoped to see whether Beck inventory scores indicating likely depression (?11) or antidepressant medicine use could predict risk progression to type 2 diabetes, and if these effects might be mediated by weight change, fasting plasma glucose, or insulin levels.

A total of 3,187 DPP participants completed the inventory and reported using antidepressants at the time of randomization and at each annual visit, for a mean of about three years.

At baseline 5.7% of patients reported taking antidepressants; 13.6% reported having taken them at any time. Seventy-eight percent of those taking antidepressants reported using a selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitors, or serotonin modulators.

The investigators found that elevated depression inventory scores, which were present in 10.3% of patients on study entry, did not predict whether patients would develop diabetes during the study, but baseline antidepressant use did.

After controlling for demographic factors, baseline metabolic factors, and weight change, they found that participants on antidepressants who were assigned to the placebo arm of the study had a hazard ratio for developing diabetes of 1.9 (95% confidence interval, 1.2-3.1, P = 0.01). For patients assigned to the intensive lifestyle group, the hazard ratio was 2.8 (95% CI, 1.5-5.4, P=0.002).

In the intensive lifestyle arm only, antidepressant user reported at 50% or more of visits also predicted developing diabetes compared to no exposure (hazard ratio 2.6, 95% CI, 1.5-4.5, P

The study was not sufficiently powered to detect which antidepressant agents might be associated with the greatest risk for type 2 diabetes, and it's not certain how the drugs might elevate risk for type 2 diabetes, but it does not appear to be through either weight gain or effects on fasting plasma glucose or insulin levels, Dr. Rubin said.

Glucophage may counteract some unknown metabolic effect of antidepressants, he added.

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