A Randomized Controlled Trial Comparing the Effects of Sitagliptin and Glimepiride on Endothelial Function and Metabolic Parameters: Sapporo Athero-Incretin Study 1 (SAIS1)

Abstract

ObjectivesThe DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride.Materials and MethodsIn this multicenter, prospective, randomized parallel-group comparison study, 103 outpatients with type 2 diabetes (aged 59.9 ± 9.9 years with HbA1c levels of 7.5 ± 0.4%) with dietary cure only and/or current metformin treatment were enrolled and randomly assigned to receive sitagliptin or glimepiride therapy once daily for 26 weeks. Flow-mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force® Monitor), and serum metabolic markers were assessed before and after the treatment.ResultsDuring the study period, no statistically significant change in %FMD was seen in both groups (sitagliptin, 5.6 to 5.6%; glimepiride, 5.6 to 6.0%). Secretory units of islets in transplantation, TNF-α, adiponectin and biological antioxidant potential significantly improved in the sitagliptin group, and superoxide dismutase also tended to improve in the sitagliptin group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.ConclusionsRegardless of glycemic improvement, early sitagliptin therapy did not affect endothelial function but may provide favorable effects on beta-cell function and on inflammatory and oxidative stress in patients with type 2 diabetes without advanced atherosclerosis.Trial RegistrationUMIN Clinical Trials Registry System UMIN 000004955

Do DPP-4 inhibitors improve endothelial cell function?

“…The original study results are illustrated in Table 1. Although glycemic control improved equally in patients treated with 50 mg/day sitagliptin or 0.5-2.0 mg/day glimepiride for 26 weeks, neither group showed improvements in FMD, even after adjustment for confounding factors [6]. Similar results were observed with another method of evaluating endothelial function, the Endo-PAT, with reactive hyperemia index being similar in the two groups.…”

“…We describe here the results of an open-label, prospective, randomized, parallel-group comparison study assessing whether the DPP-4 inhibitor sitagliptin improves endothelial cell function [6].…”

Effects of 50 mg vildagliptin twice daily <i>vs.</i> 50 mg sitagliptin once daily on blood glucose fluctuations evaluated by long-term self-monitoring of blood glucose

“…Although some hypoglycemic agents have been used to manage glycemic fluctuation, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently prescribed because of their glucose level-dependent hypoglycemic mechanism and safety profile. These drugs not only improve HbA1c and glycemic control, but also are expected to have anti-atherosclerotic and β-cell protective effects [7][8][9]. Although DPP-4 inhibitors and 2 hours after each meal, and at bedtime) once every 1 or 2 weeks for 12 weeks.…”

Comparison of the effects of empagliflozin and glimepiride on endothelial function in patients with type 2 diabetes: A randomized controlled study

“…The effects of other oral hypoglycemic agents, like pioglitazone and glucagon-like peptide 1 (GLP-1) analogs, in improving endothelial function have been reported previously [15,25]. A dipeptidyl peptidase 4 (DPP-4) inhibitor either improved [23], had no effect [26], or worsened [27] endothelial function but did not affect cardiovascular events [28,29]. In another study, GLP-1 analog treatment enhanced [30,31] or had no effect on [32] endothelial function.…”