Cardiovascular efficacy of sitagliptin in patients with diabetes at high risk of cardiovascular disease: a 12-month follow-up.

BACKGROUND: Gliptins should have beneficial effects beyond glycemic control, potentially on the pathophysiology of cardiovascular (CV) diseases, with some basic studies demonstrating this possibility. However, we are yet to answer whether there are any direct CV effects in the clinical setting. We aimed to examine the beneficial effects of sitagliptin in Japanese patients with diabetes and high CV risk for 12 months.

METHODS: This was a prospective, multicenter, observational study of 205 patients with type 2 diabetes. All participants had more than one major CV risk factor and were treated with sitagliptin for 12 months. At 3 or 12 months, we examined the effects of treatment on glycemic control, CV function (by electrocardiography, echocardiography, and reactive hyperemia-peripheral arterial tonometry), and CV biomarkers.

RESULTS: Patients were predominantly elderly (68.8 ± 9.9 years) and male (71.5 %) and typically had more than three CV risk factors (79.2 %). Treatment with sitagliptin significantly reduced the hemoglobin A1c (HbA1c) level from 7.09 % ± 0.81 % at baseline to 6.67 % ± 0.69 % at 3 months and 6.68 % ± 0.73 % at 12 months (both P < 0.001). The reduction in HbA1c was also in tandem with the decrease in the level of high-sensitive C-reactive protein throughout the study. Independent of the change in HbA1c, sitagliptin reduced systolic (-7.0 ± 18.9 mmHg) and diastolic blood pressure (-5.1 ± 11.7 mmHg) at 12 months, and this was associated with a decrease in urinary albumin. In contrast, there were no beneficial effects on cardiac and endothelial function or on the levels of serum B-type natriuretic peptide, high-sensitive troponin T, and urinary 8-hydroxy-2'-deoxyguanosine.

CONCLUSIONS: In Japanese patients with diabetes and multiple CV risk factors, sitagliptin showed a decrease in blood pressure associated with an improvement in albuminuria in addition to glycemic control.

TRIAL REGISTRATION: UMIN000005663.