Beneficial effect of combination therapy with mitiglinide and voglibose on fasting and postprandial endothelial dysfunction in patients with type2 diabetes: a pilot study

Abstract

Objective: This study was to investigate whether switching sulfonylurea to mitiglinide/voglibose could improve glycemic variability and endothelial dysfunction in patients with type 2 diabetes. Methods:This was a single arm study of 6 Japanese patients with type 2 diabetes (n =6, 5 male, 72 ± 7 year-old). Patients with 0.25-1.0 mg of glimepiride (0.8 ± 0.3 mg) with HbA1c between 6.5-7.5% were enrolled and were switched from glimepiride to mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg three times a day) for 3 months.Results: Mean amplitude of glycemic excursion (MAGE) was significantly decreased from 3.4 ± 1.3 to 1.6 ± 0.6 mmol/l (P = 0.014). Both fasting and postprandial FMD also significantly improved (5.3 ± 1.6 vs. 7.1 ± 1.7, P = 0.043 and 3.5 ± 1.5 vs. 5.2 ± 1.1, P = 0.043). The declines of insulin and C-peptide levels at 120 min were significantly correlated with the increase in postprandial FMD (r = -0.97, P = 0.013, and r = -1.00, P = 0.004). Conclusions:Glycemic variability and endothelial dysfunction at fasting and postprandial states were improved by mitiglinide/voglibose and it may be through the attenuation of hyperinsulinemia.We focused on the potential of the combination treatment to ameliorate endothelial dysfunction due to reducing the postprandial hyperglycemia [9,10], because previous studies showed that each monotherapy of glinide and α-glucosidase inhibitor ameliorated endothelial dysfunction [11,12]. In this context, we conducted this pilot study to investigate whether switching from SU to mitiglinide/ voglibose could reduce the fluctuation of blood glucose, eventually decreasing in the hypoglycemic episodes and amelioration of endothelial dysfunction in patients with type 2 diabetes. Subjects and methodsPatients with less than 1.0 mg of glimepiride (0.8 ± 0.3 mg) with HbA1c between 6.5-7.5% (n =6, 5 male, 72 ± 7 year-old) were enrolled. Two patients were treated with metformin and 1 patient with vildagliptin at the base line. The patients were switched from glimepiride to mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg Murakami M (2017) Beneficial effect of combination therapy with mitiglinide and voglibose on fasting and postprandial endothelial dysfunction in patients with type2 diabetes: a pilot study

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“…(Table-2). In the comparative study of FBS in both A and B group B mean value before treatment was 141.8±5.08 and after 3 months of the treatment was 126.12±4.02 t test value was 24.2 and P value was highly significant (P<0.01) In group mean value was before treatment 139.5±4.10 and 123.9±5.08 after treatment t test value was24.2 and P value was highly significant (P<0.01) ( Table-3) In the comparison of PBS both A and B groups-In groups A-mean value before treatment was 199.3±10.2 after 3 months 177.6 ± 7.82 t test value was16.8 and P value was highly significant (P<0.01)In group B-mean value before treatment was 207.3± 9.56 and after 3 months was 186.7 ± 10.3 t test value was 16.6 and P value was highly significant (P<0.01)(Table-4) these findings were more or less in agreement with previous studie 7,8,9 . As postprandial hyperglycemia develops early in the course of Type-2 DM and is often evident even before fasting plasma glucose (FPG) elevation was reported 10 .…”

Comparative effects of fixed‐dose mitiglinide/voglibose combination and glimepiride on vascular endothelial function and glycemic variability in patients with type 2 diabetes: A randomized controlled trial

“…Our study showed no difference in RHI between the mitiglinide/voglibose and glimepiride groups. Regarding the effects of mitiglinide/voglibose on vascular endothelial function, only one report demonstrated that fasting and postprandial FMD improved at 3 months after switching from glimepiride to mitiglinide/voglibose 15 . However, the above study was a small‐scale single‐arm pilot study involving six patients only.…”

“…A washout period of 1 day was set before switching the drugs. The reason for using glimepiride at 2 mg as the control was based on the finding of a previous study that compared mitiglinide/voglibose with glimepiride at 1 mg 15 , which showed MBG levels of 8.01 mmol/L (144.2 mg/dL) and 8.24 mmol/L ( P = 0.184), respectively. Because MBG tended to be lower for mitiglinide/voglibose, we decided to set the dose of glimepiride at 2 mg in this study.…”

“…This tablet is highly effective in lessening glycemic variability. Since glycemic variability and hypoglycemia are associated with vascular endothelial dysfunction 5 , 6 , 7 , 8 , mitiglinide/voglibose may improve vascular endothelial function, though such a possibility has so far only been described in a small‐scale pilot study 15 . To our knowledge, there are no studies that have investigated the effects of mitiglinide/voglibose on both glycemic variability and vascular endothelial function.…”

Effects of fixed-dose mitiglinide/voglibose combination on vascular endothelial function and glycemic variability in patients with type 2 diabetes: A randomized controlled trial

“…This tablet is highly effective in lessening glycemic variability. Since glycemic variability and hypoglycemia are associated with vascular endothelial dysfunction [4][5][6][7], mitiglinide/voglibose may improve vascular endothelial function, though such possibility has so far only been described in a small-scale pilot study [14]. To our knowledge, there are no studies that had investigated the effects of mitiglinide/voglibose on both glycemic variability and vascular endothelial function.…”