Journal
CIRCULATION JOURNAL
Volume 77, Issue 5, Pages 1337-1344Publisher
JAPANESE CIRCULATION SOC
DOI: 10.1253/circj.CJ-12-1168
Keywords
Dipeptidyl peptidase-4 inhibitors; Endothelial function; Inflammation
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Funding
- Ministry of Education, Science, and Culture in Japan [C22590786]
- Japan Heart Foundation Research Grant
- Japan Heart Foundation/Novartis Grant for Research Award on Molecular and Cellular Cardiology
- Sakakibara Memorial Research Grant from the Japan Research Promotion Society for Cardiovascular Diseases
- Banyu Life Science Foundation International
- Okukubo Memorial Fund for Medical Research in Kumamoto University School of Medicine
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Background: Dipeptidyl peptidase 4 (DPP4) inhibitors are used for treatment of diabetes mellitus (DM). We hypothesized that sitagliptin, a DPP4-inhibitor, could improve endothelial dysfunction in DM patients with coronary artery disease (CAD). Methods and Results: The 40 patients with CAD and uncontrolled DM, aged 68.7+/-9.4 years (mean standard deviation) (50% males, hemoglobin A(1c) [HbA(1c)] 7.4+/-1.0%) were assigned to either additional treatment with sitagliptin (50 mg/day, n=20) or aggressive conventional treatment (control, n=20) for 6 months. Endothelial function was assessed by the reactive hyperemia peripheral arterial tonometry index (RHI). The clinical characteristics at baseline were not different between the groups. After treatment, fasting blood glucose and insulin levels, and lipid profiles were not different between the groups. HbA(1c) levels significantly improved similarly in both groups. The percent change in RHI was greater in the sitagliptin group than in the control group (62.4+/-59.2% vs. 15.9+/-22.0%, P<0.01). Furthermore, treatment with sitagliptin resulted in a significant decrease in the high-sensitivity C-reactive protein (hsCRP) level, but no such change was noted in the control group. Linear regression analysis demonstrated a significant negative relation between changes in RHI and hsCRP, but not between RHI and HbA(1c). Conclusions: Sitagliptin significantly improved endothelial function and inflammatory state in patients with CAD and uncontrolled DM, beyond its hypoglycemic action. These findings suggest that sitagliptin has beneficial effects on the cardiovascular system in DM patients. (Circ J 2013; 77: 1337-1344)
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