Coronary Artery Disease
Impact of Sitagliptin on Carotid Intima-Media Thickness in Patients With Coronary Artery Disease and Impaired Glucose Tolerance or Mild Diabetes Mellitus

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Sitagliptin has been widely used for the treatment of diabetes and shown recently to have beneficial pleiotropic outcomes on cardiovascular systems in experimental studies. However, little is known about the influence of sitagliptin on atherosclerosis-related cardiovascular diseases in a clinical setting. This study examined the effect of sitagliptin on carotid intima-media thickness (IMT). A total of 76 patients with clinically stable and documented coronary artery disease, who were newly diagnosed with impaired glucose tolerance or mild type 2 diabetes mellitus, were allocated, randomly, to receive either sitagliptin 100 mg/day or the placebo control. Common carotid IMT, glucose profiles, glycosylated hemoglobin (HbA1c), and lipid profiles were measured at baseline and repeated at 12 months. Sitagliptin-treated patients showed less IMT progression than the control group (p = 0.02). In addition, the sitagliptin group showed greater reductions in body weight (2.2%), 2-hour glucose levels on the 75-g oral glucose tolerance test (17.3%), HbA1c (4.7%), and low-density lipoprotein cholesterol levels (7.9%) from that at baseline. In conclusion, treatment with sitagliptin for 12 months was associated with a beneficial effect in the prevention of carotid IMT progression, compared with the diet control.

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Methods

This study was a prospective, randomized, open-label, single-center, parallel-group, comparative trial. The trial is known as the “early treatment of glucose toxicity with Sitagliptin Prevent progression of ARteriosclerosis in Cardiovascular disease patients” study, was registered at https://center.umin.ac.jp as UMIN 000006432, and was approved by the hospital ethics committee. Participants were recruited from patients admitted to the Department of Cardiology at Anjyo Kosei Hospital (Anjyo,

Results

A total of 80 patients were enrolled in the study, with 40 patients in each group. One patient in the sitagliptin group discontinued antidiabetic therapy owing to drug-related nausea, and 1 patient in each group was withdrawn because of newly identified cardiovascular events. An additional 2 patients in the sitagliptin group were lost to follow-up. Thus, complete baseline and follow-up data were available for 37 patients in the sitagliptin group and 39 in the control group. The baseline

Discussion

This small, prospective, open-label, randomized study demonstrated, for the first time, that 12 months of treatment with sitagliptin was associated with a beneficial effect in terms of preventing the progression of carotid IMT. However, the use of sitagliptin was not associated with a significant decrease in IMT from baseline.

The treatment options for T2DM have expanded since the development of several DPP-4 inhibitors. There is a growing body of evidence that these agents may have protective

Acknowledgment

The authors gratefully acknowledge the technical assistance of Akihiro Suzuki, BSc.

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    This work was supported by grant YRY1311 from Yokoyama Foundation for Clinical Pharmacology, Nagoya, Japan to Dr. Shimano.

    This trial is registered at http://center.umin.ac.jp; unique identifier: UMIN (University Hospital Medical Information Network) 000006432.

    See page 387 for disclosure information.

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