Antidepressant use associated with increased type 2 diabetes risk

Caroline Cassels

June 15, 2006

June 15, 2006

Washington, DC - A new study has linked antidepressant use to a more than threefold increased risk of type 2 diabetes in prediabetic individuals [ 1 ].

Presenting here at the American Diabetes Association 2006 Scientific Sessions, researchers found patients participating in the Diabetes Prevention Program (DPP) who were taking antidepressant agents at baseline or who took them frequently during the study were two to three times more likely to develop diabetes, suggesting antidepressant medications predispose to diabetes.

Drs Richard Rubin and David Marrero

"At this point we really don't understand what's going on. This is the first study to report this association, but it is important to remember that these are preliminary results that require further investigation. Nevertheless, with 40 million people [in the US] at risk of developing diabetes and more than 10 million Americans taking antidepressant medications, this is a major public-health issue," principal investigator Dr Richard Rubin (Johns Hopkins University School of Medicine, Baltimore, MD) told renal wire .

Launched in 1997, the DPP is a multicenter longitudinal study designed to determine whether diabetes onset can be prevented or delayed in high-risk individuals through intensive lifestyle modification or treatment with metformin (Glucophage, Merck & Co) compared with placebo.

Chicken-and-egg scenario

While it has long been acknowledged by the scientific community there is a link between type 2 diabetes and depression, it is not clear from the existing research which comes first. In this current analysis, researchers used data from the DPP to try to sort out the link between these two common diseases.

Researchers looked at Beck Depression Inventory (BDI) scores indicating likely depression or antidepressant use to determine whether either predicted progression to type 2 diabetes in a DPP cohort of 3187 participants.

Study subjects were aged 25 years or older with impaired glucose tolerance, elevated fasting glucose, and a body-mass index (BMI) of >24 kg/m 2. For Asian Americans, a BMI of 22 kg/m 2 was used.

Eligible participants were randomized to one of three interventions. The placebo arm included patients who received standard lifestyle recommendations plus a placebo pill twice daily. The metformin subjects incorporated standard lifestyle recommendations and 850 mg of twice-daily metformin. Subjects in the intensive-lifestyle arm were supported in achieving and maintaining a weight reduction of at least 7% of initial body weight through a calorie-controlled, low-fat diet and had to engage in physical activity of moderate intensity for at least 150 minutes per week.

Diabetes status, depression symptoms, physical-activity levels, and insulin secretion and resistance were all assessed at baseline and annually during the study. Antidepressant medication use was assessed at baseline and then quarterly.

At baseline, 10.3% of study participants had elevated BDI scores >11, and baseline antidepressant use was present in 5.3% of the study population. Rubin said investigators were surprised to find that while baseline depression did not predict the development of diabetes, antidepressant use did.

"We found that having elevated depressive symptoms at any time during the study did not predict the development of [type 2] diabetes in any of the DPP arms. But those in the placebo arm who were taking antidepressants had more than twice the risk and antidepressant users in the lifestyle group more than three and a half times the risk of developing diabetes," Rubin said.

Does metformin have a protective effect?

Even more surprising, he added, was that there was no increased risk of developing diabetes among subjects in the metformin arm who were taking antidepressants.

Whether metformin has a protective effect is not yet clear, said Rubin, adding that his team is currently trying to determine potential mechanisms that might explain this finding.

Baseline antidepressant use was also associated with an increased risk of type 2 diabetes. In addition, patients' length of exposure to antidepressants also affected diabetes risk. With an average follow-up of 3.2 years, the study found that those who took antidepressants up to 75% of the time did not increase their risk of developing type 2 diabetes. But those who took antidepressant medication 88% to 100% of the time (mean 99%) had the same elevated risk of developing diabetes as those who were taking antidepressants at baseline. Again, there was a more than twofold increased risk for the placebo group and over threefold for the intensive-lifestyle group but not in the metformin arm of the study.

Redoubling diabetes prevention efforts

While it was not possible to look at use of specific agents, study subjects were mainly taking selective serotonin reuptake inhibitors and related medications that have previously been thought to be least likely to cause diabetes because they caused weight loss or were weight neutral, said Rubin. But in multivariate analysis, which controlled for demographic factors, baseline metabolic factors, and weight change, the antidepressant effect on type 2 diabetes risk remained.

At this point, patients should not discontinue antidepressant therapy, said Rubin. "These are preliminary findings that need to be followed up. Antidepressants are tremendously important for people suffering from depression."

However, study coauthor Dr David Marrero (Indiana University School of Medicine, Indianapolis) said that in light of these findings physicians should consider the role of depression and exposure to antidepressant therapy when counseling high-risk patients.

"If somebody came to me and had all the classic risk factors for diabetes coupled with a history of depression and/or depression medication, these data would suggest to me that I should renew the intensity of my efforts and try to promote lifestyle modification in that individual," he told renalwire . In addition, he said, lifestyle therapy may also attenuate depression risk.

Rubin agreed and said physicians should also consider counseling as a form of antidepressant therapy.

"This is a big study, it's the first time it's ever been done, and it is a major public-health concern. But these are still preliminary findings, and we must continue to understand this better," said Rubin.


  1. Depression symptoms, antidepressant medication use, and risk of developing diabetes in Diabetes Prevention Program participants. American Diabetes Association 2006 Scientific Sessions; June 9-13, 2006; Washington, DC. Abstract 896-P.


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