Impact of teneligliptin on oxidative stress and endothelial function in type 2 diabetes patients with chronic kidney disease: a case–control study

Abstract

BackgroundThe aim of the present study was to elucidate the effect of teneligliptin on oxidative stress and endothelial function in Japanese patients with type 2 diabetes and chronic kidney disease (CKD).MethodsForty-five patients with type 2 diabetes and CKD who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) for 24 weeks. The following parameters were evaluated at baseline and after 24 weeks of treatment with continued sitagliptin or teneligliptin: blood pressure, haemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), urinary albumin excretion, endothelial function by reactive hyperaemia index (RHI; EndoPAT® system), reactive oxygen metabolites (ROMs) measured by the d-ROMS test, 8-hydroxy-2′-deoxyguanosine, urinary liver-type fatty acid binding protein (L-FABP), and urinary 8-isoprostane.ResultsThe two groups did not significantly differ with regard to age, male-to-female ratio, duration of diabetes, body mass index, HbA1c, eGFR, or urinary albumin excretion levels at baseline. We found no significant differences in changes of HbA1c, eGFR, or urinary albumin excretion levels between the two groups after 24 weeks of treatment. However, treatment with teneligliptin, but not sitagliptin, significantly improved RHI values and was correlated with the percent changes in RHI and d-ROMs.ConclusionsThe present study demonstrated that teneligliptin, can improve endothelial function and reduce renal and vascular oxidative stress in patients with type 2 diabetes and CKD, independently of reducing albuminuria or improving glucose control.Trial registration UMIN000017180

Effect of switching to teneligliptin from other dipeptidyl peptidase‐4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease

“…Therefore, the D%DPP-4 after switching to teneligliptin strongly contributes to the D%UACR, independently of the change in glucose control, BMI and BP, plasma DPP-4 activity, and FPG at baseline. By contrast, Sagara et al 34 previously showed that teneligliptin switching from sitagliptin can improve endothelial function, and reduce renal and vascular oxidative stress in patients with type 2 diabetes mellitus and CKD compared with those taking sitagliptin. The effect of teneligliptin was independent of improving glucose control, and the amount of albuminuria showed no significant difference between teneligliptin and sitagliptin treatment 34 .…”

“…previously showed that teneligliptin switching from sitagliptin can improve endothelial function, and reduce renal and vascular oxidative stress in patients with type 2 diabetes mellitus and CKD compared with those taking sitagliptin. The effect of teneligliptin was independent of improving glucose control, and the amount of albuminuria showed no significant difference between teneligliptin and sitagliptin treatment. However, because they did not assess plasma DPP‐4 activity, the relationship between the change in DPP‐4 activity and UACR is unclear.…”

Vildagliptin improves high glucose‐induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission

“…Furthermore, excessive production of ROS and subsequent decrease in NO production result in endothelial dysfunction. Previous studies have shown that teneligliptin reduces vascular oxidative stress in patients with T2DM …”

Effect of growth hormone replacement therapy on plasma diacron-reactive oxygen metabolites and endothelial function in Japanese patients: The GREAT clinical study

“…In addition, the period of improvement of RHI and d-ROMs by reducing some risk factor for the onset of cardiovascular disease (i.e. hypertension, diabetes, dyslipidemia) were generally 3-6 months in another clinical study [14,[16][17]38]. Therefore, we thought 24 weeks after demonstrating the normal range of IGF-1 levels might be adequate to verify the effects of GH replacement therapy.…”

“…Reactive hyperemia peripheral arterial tonometry (RH-PAT), using an EndoPAT2000 device (Itamar Medical, Caesarea, Israel), is a validated methodology that is described in the literature [14][15][16]. A blood pressure cuff was placed on the subject's upper arm, while the contralateral arm served as control [14].…”