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Sitagliptin Shows Anti-inflammatory Activity in Diabetes Patients

Posted: Wednesday, July 20, 2011

The dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin exerts an anti-inflammatory effect in patients with type 2 diabetes at the cellular and molecular level.

Paresh Dandona, MD, chief of endocrinology at the State University of New York at Buffalo, and colleagues randomized 22 type 2 patients to 12 weeks' treatment with either 100 mg daily of sitagliptin or placebo.

The investigators had hypothesized that since DPP-4 is expressed as CD26 on cell membranes and also mediates pro-inflammatory signals, sitagliptin may have an anti-inflammatory effect.

Results of fasting blood samples showed that sitagliptin induced a reduction in the expression of a series of pro-inflammatory genes in mononuclear cells MNC including TLR-4, IKK- beta, JNK, and CCR-2. Plasma concentrations of CRP, TNF- alpha and Il-6 were also significantly reduced. Placebo treatment produced no change.

Dr. Dandona noted that, there was also a significant, steady reduction in plasma FFA concentrations. "This action may help reduce inflammation since increased FFA concentrations induce oxidative and inflammatory stress and also induce resistance to the action of insulin."

The decrease in FFA concentrations may be due to an increase in the bio-availability of insulin following sitaglipin treatment, he added.

Notably, there was no significant change in fasting blood glucose concentrations while HbA1c decreased significantly.

Dr. Dandona said that the results of this small study show that sitagliptin exerts a comprehensive anti-inflammatory effect. This effect may over the long-term contribute to a reduction in atherogenesis, thereby leading to a decrease in cardiovascular events, he said.

Source:, Reported at the 71st Scientific Sessions of the American Diabetes Association, June 2011.

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