Mechanism of Imeglimin effect on glucose metabolism by a 75g oral glucose tolerance test with double-tracer

JRCT ID: jRCTs031210600

Registered date:07/02/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus
• Date of first enrollment: 23/07/2022
• Target sample size: 25
• Study type: Interventional
• Intervention(s): Patients will be orally administered 1000 mg of Imeglimin twice daily in the morning and evening for 20 weeks, and will undergo blood sampling and other diabetes-related tests, biofunctional tests, and muscle biopsy.

Outcome(s)

• Primary Outcome: Changes in area under the curve (AUC0-3h glucose) from 0 hour to 3 hours after glucose loading in 75g oral glucose tolerance test (OGTT) from before the start of Imeglimin treatment to 20 weeks after the start of treatment

Secondary Outcome

1) Change in AUC0-3h glucose during 75g OGTT from before to 1 week after imeglimin administration
2) Changes in AUC0-1h glucose, AUC0-2h glucose, and AUC0-4h glucose during 75 g OGTT from before to 1 week after the start of Imeglimin treatment and at 20 weeks after the start of treatment
3) Changes in glucose over time at each assessment time point during 75 g OGTT
4) Changes in insulin , C-peptide , glucagon , and free fatty acids over time at each assessment time point during 75g OGTT
5) Changes in GLP-1 and GIP over time at each assessment time point during 75g OGTT
6) Changes in rate of orally ingested glucose appearance (Ra oral), endogenous glucose production (Ra (EGP)), and rate of glucose disappearance (Rd: rate of disappearance) during 75g OGTT
7) Changes in insulin secretion capacity (AUC insulin / AUC glucose, insulinogenic index), insulin sensitivity (Matsuda index), and glucose tolerance (AUC0-3h glucose, AUC0-3h Insulin)
8) Changes in hepatic intracellular lipid (IHL), skeletal muscle intracellular lipid (IMCL), visceral fat area, and subcutaneous fat area
9) Changes in skeletal muscle insulin sensitivity (Rd), liver insulin sensitivity, adipose tissue insulin sensitivity, insulin clearance, and feedback inhibition of insulin secretion
10) Changes in resting basal metabolism, metabolic flexibility, resting endogenous glucose production, and maximal oxygen uptake
11) Mitochondrial mass by muscle biopsy
12) Changes in body weight and body composition
13) Improvement in blood and urine collection

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 65age old
• Gender: Both

Include criteria

1) Patients with type 2 diabetes mellitus who are between 20 and 65 years old at the time of obtaining informed consent
2) BMI range 18.5 kg/m2-30.0 kg/m2 at screening
3) HbA1c level range 6.5%-10.0% at screening
4) Patients who have not received any hypoglycemic drug other than metformin at the time of obtaining informed consent
5) Patients who have not changed their diabetic medication (add-on, discontinuation, or dose modification) within 12 weeks prior to obtaining informed consent
6) Patients who have voluntarily provided written informed consent on the basis of proper understanding of sufficient explanations given before participation in this study

Exclude criteria

1) Patients with type 1 diabetes mellitus
2) Patients with contraindications to Imeglimin
3) Patients with severe liver disease (e.g., decompensated hepatic cirrhosis ) or AST or ALT greater than 100 IU/L at screening
4) Patients with renal disease or with an estimated glomerular filtration rate (eGFR) of less than 45 mL/min/1.73m2 at screening
5) Patients with serious cardiac disease (e.g., cardiac failure, unstable angina pectoris) or who have had a myocardial infarction or angina attack within 24 weeks prior to obtaining informed consent
6) Patients who have had a stroke attack (cerebral infarction, cerebral hemorrhage) within 24 weeks prior to obtaining informed consent
7) Patients with malignancy
8) Patients with severe diabetic complications (neuropathy, retinopathy, nephropathy)
9) Patients in severe ketosis, diabetic coma, or precoma
10) Patients with endocrine disorders (e.g., pituitary, thyroid, adrenal) inadequately treated with hormone replacement therapy, etc.
11) Patients with moderate or severe anemia (hemoglobin (Hb) less than 9.5 g/dL)
12) Patients who are heavy drinkers (average daily alcohol consumption of more than 3 glasses (one glass: 180 ml) of sake or 3 large beer bottles)
13) Patients who are pregnant, lactating or have the possibility of pregnancy during the study period
14) Other patients deemed inappropriate by the principal investigator or sub-investigator

Related Information

• Primary Sponsor: Kaga Hideyoshi
• Source(s) of Monetary Support: Sumitomo Pharma Co., Ltd.