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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Imeglimin; Drug: Metformin; Drug: Vildagliptin

• Study Type: Interventional
• Enrollment (Estimated): 567
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Shinjuku-Ku, Tokyo, Japan, 162-8655
      • Center Hospital of the National Center for Global Health and Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients diagnosed with type 2 diabetes mellitus who are 20 years of age or older at the time of obtaining consent.
2. 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.
3. Patients whose HbA1c level is between 7.0% and 9.0% as measured at the time of the eligibility test.
4. Patients who have given written consent to participate in this study.

Exclusion Criteria:

When consent is obtained

1. Patients with type 1 diabetes mellitus
2. Patients who have been given more than 2 oral hypoglycemic drugs within 12 weeks
3. 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
4. Patients with proliferative retinopathy (except for patients with stable treated proliferative retinopathy)
5. Patients with severe diabetic neuropathy (patients with severe symptoms and significant support for daily life)
6. Patients with a contraindication to Imeglimin, Metformin, or Vildagliptin
7. Patients with severe obesity (BMI 35 kg/m^2 or more)
8. Patients with NYHA (New York Heart Association) cardiac function classification of Grade III or IV within 1 year of evaluation
9. Excessive regular drinkers
10. Patients with a previous history of lactic acidosis
11. Patients with severe cachexia, diabetic coma or precoma
12. Patients with severe infections, surgical patients and those with serious injuries
13. Patients who are pregnant, who are planning to be pregnant, or who are breastfeeding
14. Patients who are undergoing treatment for malignancy or those with a history of treatment for malignancy within 5 years
15. Patients who are participating in a clinical study with other interventions
16. Patients to whom a responsible physician/investigator judged inappropriate for participating in the study In case of eligibility testing
17. Patients with an estimated glomerular filtration rate(eGFR) of 45 mL/min/1.73m^2 or less including those undergoing dialysis
18. Patients with severe hepatic disorders (Child-Pugh classification Grade C)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imeglimin; Imeglimin 1000 mg orally twice daily in the morning and evening (2000 mg daily).	Drug: Imeglimin; Imeglimin 1000 mg orally twice daily in the morning and evening (2000 mg daily).
Active Comparator: Metformin; 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; 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.
Active Comparator: Vildagliptin; Vildagliptin 50 mg orally twice daily in the morning and evening (100 mg daily).	Drug: Vildagliptin; Vildagliptin 50 mg orally twice daily in the morning and evening (100 mg daily).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: National Center for Global Health and Medicine, Japan
• Collaborators: Sumitomo Pharma Co., Ltd.
• Investigators: Principal Investigator: Kohjiro Ueki, M.D., Ph.D., Center Hospital of the National Center for Global Health and Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2022
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 15, 2022
• First Submitted That Met QC Criteria: May 5, 2022
• First Posted (Actual): May 9, 2022

Study Record Updates

• Last Update Posted (Actual): April 9, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitriles; Pyrrolidines; Biguanides; Guanidines; Amidines; Vildagliptin; Metformin; imeglimin
• Other Study ID Numbers: 004371; jRCTs051180211 (Registry Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No