Abstract
BackgroundGliptins 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.MethodsThis 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.ResultsPatients 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.ConclusionsIn 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: UMIN000005663Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0371-z) contains supplementary material, which is available to authorized users.
Highlights
Gliptins should have beneficial effects beyond glycemic control, potentially on the pathophysiology of cardiovascular (CV) diseases, with some basic studies demonstrating this possibility
Type 2 diabetes is strongly associated with coronary atherosclerosis and vascular complications, both of which are responsible for worse morbidity and mortality [1]
Integrated behavior modification and targeted polypharmacy are especially beneficial for patients with diabetes who are at high risk of CV disease (CVD) [5]
Summary
Gliptins should have beneficial effects beyond glycemic control, potentially on the pathophysiology of cardiovascular (CV) diseases, with some basic studies demonstrating this possibility. Integrated behavior modification and targeted polypharmacy are especially beneficial for patients with diabetes who are at high risk of CV disease (CVD) [5]. Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor (gliptin), has been shown to increase plasma incretin hormone levels, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Increases in these peptides appear to be responsible for the principle mechanism of action of sitagliptin; as the levels of GLP-1 increase, glucose concentrations decrease [6]. We still do not know the various long-term influences of incretin-based therapies, such as sitagliptin, on CV risk factors and disease, including the effects on morbidity and mortality
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