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Diabetes Drugs May Reduce Risk for Affective Disorders

Sulfonylureas and metformin may help to reduce the risk for depression….

The increased risk for depression and other affective disorders seen in patients with type 2 diabetes (T2DM) is minimized by oral antihyperglycemic treatment with sulfonylurea and metformin, a new study suggests.

The findings build on prior research that has shown that mood disorders, including depression as well as the neurodegenerative diseases dementia and Parkinson’s disease, are more common among patients with T2DM and that treatment with metformin may help reduce the risk.

Mark L. Wahlqvist, MD, professor emeritus, Monash University and the Monash Asia Institute, Victoria, Australia, who led the new study wrote, "We wondered if there might be some common underlying mechanism which predisposes to neurodegenerative disease and depression or affective disorders."

"Since we have now found that metformin usage is associated with less affective disorder, we think our hypothesis has considerable merit. It also points to problems of energy regulation in the brain, as elsewhere in the body, as a mechanism," he said.

To determine the effect on risk for affective disorder with T2DM, with and without oral antihyperglycemic agents (OAA), Dr. Wahlqvist and colleagues followed a representative sample of 762,753 Taiwanese adults for 12 years.

For patients with T2DM aged 50 years and older, having no OAA therapy was a risk factor for affective disorder, with an overall hazard ratio (HR) of 2.62 (95% confidence interval [CI], 2.31 – 2.98), they report.

This finding, researchers note, "suggests that available studies have grossly underestimated the potential effect of diabetes in this area of mental health."

They also report that the combination of sulfonylurea and metformin (but not either one alone) significantly reduced both the incidence and relative risk for affective disorder in association with T2DM.

The HR for affective disorder was 0.92 (95% CI, 0.59 – 1.45) for patients receiving metformin alone, 1.08 (95% CI, 0.84 – 1.38) for those receiving sulfonylurea alone, and 0.40 (95% CI, 0.32 – 0.50) for those receiving combined treatment. These findings are "consistent with synergistic or complimentary mechanisms of action" of the 2 agents, the authors write.

"As the global burden of diabetes increases, these findings may be relevant to the reduction of its mental-health consequences," the researchers write.

BMC Med. Published online November 29, 2012. Abstract, Editorial