Glucose excursions and hypoglycemia in patients with type 2 diabetes treated with mitiglinide/voglibose versus glimepiride: A randomized cross‐over trial

Abstract

Background: Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy. Methods: This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test. Results: The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase. Conclusions: Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

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

“…Other indices of glycemic variability, such as SD and CV, were also significantly lower for mitiglinide/voglibose. Fujimoto et al 14 . compared the effects of mitiglinide/voglibose and glimepiride (1.0 mg/day) using a crossover design, similar to our study, and reported that MAGE for mitiglinide/voglibose was 62.46 mg/dL, significantly lower than for glimepiride (95.04 mg/dL).…”

“…One previous study of 20 patients described a significant difference in glycemic variability between mitiglinide/voglibose and glimepiride 14 , but no previous studies have investigated vascular endothelial function. Therefore, the aim of our study was to conduct exploratory evaluation of the assessment parameters, and a sample size of 30 cases was determined as feasible within the planned registration period.…”

“…Oral hypoglycemic agents that are considered effective, especially in improving postprandial hyperglycemia, include α‐glucosidase inhibitors (α‐GIs) 12 and rapid‐acting insulin secretagogues 13 . The fixed‐dose mitiglinide/voglibose combination tablet (hereinafter referred to as mitiglinide/voglibose), which contains a rapid‐acting insulin secretagogue (mitiglinide calcium hydrate) and an α‐GI (voglibose), has evidenced promise in improving postprandial hyperglycemia and in reducing hypoglycemic events 14 . This tablet is highly effective in lessening glycemic variability.…”

Safety, tolerability, pharmacokinetics, and pharmacodynamics of the glucokinase activator PB-201 and its effects on the glucose excursion profile in drug-naïve Chinese patients with type 2 diabetes: a randomised controlled, crossover, single-centre phase 1 trial

“…The daily blood glucose curve with PB-201 had a similar shape but shifted downwards compared with placebo, indicating that PB-201 may have an impact on fasting glucose rather than postprandial glucose. This trajectory is in contrast with the flattened curve under treatment with mitiglinide/voglibose, which lowered glucose fluctuations postmeal [32]. The mechanism of action behind this may be PB-201's constant activation of glucokinase in the liver.…”

Hypoglycemia possibly caused by CYP2C9-mediated drug interaction in combination with bucolome: a case report

“…Based on the pharmacological mechanism, it is unlikely that an α-glucosidase inhibitor alone can induce hypoglycemia. The incidence of hypoglycemia with voglibose alone is lower than that with other antidiabetic drugs [ 23 , 24 ]. In this case, there were no complications, such as other diseases and infections, and the patient was consuming food without any problems.…”