Durable Effect of Imeglimin on the Glycemic Control in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Study subjects will be randomly assigned to the three groups and receive the study drug for maximum of 156 weeks and undergo blood samplings and other diabetes mellitus-related tests. The aim of the present study is to evaluate the durability of glycemic control over 3 years for patients with type 2 diabetes on diet and exercise therapy treated with oral hypoglycemic drug monotherapy.

Official Title
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Durable Effect of Imeglimin on the Glycemic Control in Patients With Type 2 Diabetes Mellitus: a Multicenter, Open-label, Randomized, Controlled Trial (DIGNITY Trial)

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Imeglimin
* Drug: Metformin
* Drug: Vildagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with type 2 diabetes mellitus who are 20 years of age or older at the time of obtaining consent. Patients being treated with diet and exercise therapy only at the time of eligibility test However, if the patient is taking one oral hypoglycemic drug at the time of obtaining consent, the patient must be able to wash out the oral hypoglycemic drug for at least 12 weeks before the start of study treatment. Patients whose HbA1c level is between 7.0% and 9.0% as measured at the time of the eligibility test. Patients who have given written consent to participate in this study. Exclusion Criteria: When consent is obtained Patients with type 1 diabetes mellitus Patients who have been given more than 2 oral hypoglycemic drugs within 12 weeks Patients who have received glucagon like peptide-1 receptor agonist (short-term use of insulin for trauma or educational admission) within 1 year or less Patients with proliferative retinopathy (except for patients with stable treated proliferative retinopathy) Patients with severe diabetic neuropathy (patients with severe symptoms and significant support for daily life) Patients with a contraindication to Imeglimin, Metformin, or Vildagliptin Patients with severe obesity (BMI 35 kg/m^2 or more) Patients with NYHA (New York Heart Association) cardiac function classification of Grade III or IV within 1 year of evaluation Excessive regular drinkers Patients with a previous history of lactic acidosis Patients with severe cachexia, diabetic coma or precoma Patients with severe infections, surgical patients and those with serious injuries Patients who are pregnant, who are planning to be pregnant, or who are breastfeeding Patients who are undergoing treatment for malignancy or those with a history of treatment for malignancy within 5 years Patients who are participating in a clinical study with other interventions Patients to whom a responsible physician/investigator judged inappropriate for participating in the study In case of eligibility testing Patients with an estimated glomerular filtration rate(eGFR) of 45 mL/min/1.73m^2 or less including those undergoing dialysis Patients with severe hepatic disorders (Child-Pugh classification Grade C)

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Imeglimin<br>Imeglimin 1000 mg orally twice daily in the morning and evening (2000 mg daily). | Drug: Imeglimin<br>* Imeglimin 1000 mg orally twice daily in the morning and evening (2000 mg daily).<br>|
| Active Comparator: Metformin<br>Metformin 500 mg orally twice daily in the morning and evening (1000 mg daily). However, until 2 weeks after the start of treatment, 250 mg should be administered orally twice daily in the morning and evening. Thereafter, after 4, 8, or 12 weeks, the dose may be increased up to 750 mg twice daily (1500 mg daily) if the physician determines that the hypoglycemic effect is inadequate. | Drug: Metformin<br>* Metformin 500 mg orally twice daily in the morning and evening (1000 mg daily). However, until 2 weeks after the start of treatment, 250 mg should be administered orally twice daily in the morning and evening. Thereafter, after 4, 8, or 12 weeks, the dose may be increased up to 750 mg twice daily (1500 mg daily) if the physician determines that the hypoglycemic effect is inadequate.<br>|
| Active Comparator: Vildagliptin<br>Vildagliptin 50 mg orally twice daily in the morning and evening (100 mg daily). | Drug: Vildagliptin<br>* Vildagliptin 50 mg orally twice daily in the morning and evening (100 mg daily).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from study drug initiation (Week 0) to detection of two consecutive HbA1c levels of 7.0% or higher by laboratory tests after Week 16. |  | From 16 to 156 weeks after the start of study drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from Week 0 to addition of a type 2 diabetes mellitus medication after Week 16 |  | From 16 to 156 weeks after the start of study drug administration | 
| Time from detection of two consecutive HbA1c levels of 7.0% or higher to addition of a type 2 diabetes mellitus medication after Week 16. |  | From 16 to 156 weeks after the start of study drug administration | 
| HbA1c level, fasting blood glucose level, and their changes from baseline at each measurement point |  | From 0 to 156 weeks after the start of study drug administration | 
| Maximum decrease in HbA1c level during the observation period |  | From 0 to 156 weeks after the start of study drug administration | 
| Proportion of patients achieving HbA1c level less than 7.0% at each measurement point |  | From 0 to 156 weeks after the start of study drug administration | 
| Number of times of achieving HbA1c level less than 7.0% during the observation period |  | From 0 to 156 weeks after the start of study drug administration | 
| Time from Week 0 to detection of two consecutive HbA1c levels of 7.0% or higher by laboratory tests after Week 16 by patient characteristics |  | From 0 to 156 weeks after the start of study drug administration |