The effect of mitiglinide calcium hydrate/voglibose on vascular endothelial function and blood glucose fluctuation in patients with type 2 diabetes - Low-dose glimepiride controlled crossover study -

JRCT ID: jRCTs071190047

Registered date:20/02/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus
• Date of first enrollment: 08/02/2021
• Target sample size: 30
• Study type: Interventional

Intervention(s)

mitiglinide/voglibose fixed-dose combination (M/V) precedent group: After 5 days observation period, patients receive treatment with M/V (mitiglinide 10mg/voglibose 0.2 mg, three times a day) for 5 days from the 6th day of study treatment (first period). On the 11th day of study treatment, washout is performed for 1 day. On the 12th day of study treatment, patients receive treatment with glimepiride (2.0 mg, Once a day) for 5 days (second period).
Low-dose glimepiride precedent group: After 5 days observation period, patients receive treatment with glimepiride (2.0 mg, Once a day) for 5 days from the 6th day of study treatment (first period). On the 11th day of study treatment, washout is performed for 1 day. On the 12th day of study treatment, patients receive treatment with M/V (mitiglinide 10mg/voglibose 0.2 mg, three times a day) for 5 days (second period).

Outcome(s)

Primary Outcome

1) reactive hyperemia index: RHI
2) mean amplitude of glycemic excursions: MAGE

Secondary Outcome

<efficacy endpoints>
CGM Parameter:
1) Mean of Blood glucose
2) SD of Blood glucose
3) CV of Blood glucose
4) Estimated HbA1c (eA1c)
5) AUC or AOC of blood glucose response curve
<54 mg/dL*, <70 mg/dL*, 70 to 180 mg/dL, 140 mg/dL<, 180 mg/dL<, 200 mg/dL< and 250 mg/dL< (*AOC)
6) Percentage of time (%)
<54 mg/dL, <70 mg/dL, 70 to 180 mg/dL, 140 mg/dL<=, 180 mg/dL<=, 200 mg/dL<= and 250 mg/dL<=
7) mean postprandial glucose excursion (MPPGE)
8) low blood glucose index (LBGI)
9) high blood glucose index (HBGI)
10) Predicted % of BG 70 mg/dL

# Evaluate in 3 categories (24 hours, 0:00-7:00, 7:00-24:00), except MPPGE.

Oxidative stress marker:
urinary 8-OHdG

Relationship between vascular endothelial function and blood glucose fluctuation:
The factors affecting reactive hyperemia index (RHI)

<safety endpoints>
adverse events and adverse drug reactions

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

1) Patients diagnosed with type 2 diabetes (diagnostic criteria according to Japanese clinical practice guideline for Diabetes 2016)
2) Patients with 7.0% or more and less than 10.0% of HbA1c measured within 2 months before enrollment
3) Patients being treated with metformin (include combination therapy of DPP-4 inhibitor)
4) Patients hospitalized or scheduled to be hospitalized during the study period for the treatment of diabetes
5) Patients who are 20 years old or older to under 80 years old at the time of obtaining consent
6) Patients who agreed in writing about participation in the study

Exclude criteria

1) Patients who are being treated with hypoglycemic agents (including insulin therapy) other than Metformin (include combination therapy of DPP-4 inhibitor)
2) Patients with fasting blood glucose 200 mg/dL or more measured within 2 weeks before enrollment
3) Patients with severe liver dysfunction (AST or ALT, over 100 IU / L measured within 2 weeks before enrollment)
4) Patients with severe renal dysfunction (eGFR, less than 30 mL/min/1.73 m^2 measured within 2 weeks before enrollment)
5) Patients with severe ketosis, diabetic coma or pre-coma, and insulin-dependent diabetes (such as juvenile-type diabetes, brittle-type diabetes, and type 1 diabetes)
6) Patients with severe infection, before and after surgery, severe injury
7) Patients with gastrointestinal disorders such as diarrhea and vomiting
8) Patients who are pregnant or may be pregnant
9) Patients with a history of hypersensitivity to components of mitiglinide/voglibose fixed-dose combination and glimepiride or sulfonamides
10) Others, patients judged to be unsuitable for this study by investigators

Related Information

• Primary Sponsor: Okada Yosuke
• Source(s) of Monetary Support: KISSEI PHARMACEUTICAL CO., LTD.