Investigation of the mechanism of action of imeglimin using the glucose clamp test

JRCT ID: jRCTs051220028

Registered date:25/05/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus
• Date of first enrollment: 06/07/2022
• Target sample size: 30
• Study type: Interventional
• Intervention(s): Oral administration of Imeglimin (1000 mg twice a day) or metformin (250 mg twice a day for the first 4 weeks, increasing to 500 mg twice a day after 4 weeks) for 16 weeks

Outcome(s)

• Primary Outcome: Area under the curve of insulin concentration in the hyperglycemic clamp between 0 and 10 minutes after 16 weeks of study drug administration (incremental AUCIRI0-10)

Secondary Outcome

<Efficacy endpoints>
1) Change in HbA1c from the start of study drug administration to 16 weeks after the start of study drug administration
2) Change in various glucose metabolism indices (insulinogenic index, HOMA-beta, AUC IRI120 /AUC PG120, HOMA-R, composite index, oral disposition index, proinsulin/insulin and AUC PG120)
proinsulin/insulin = proinsulin (pmol/L) / insulin (microU/mL) x 6.945
3) Glucose infusion rate (GIR) and insulin sensitivity index (ISI) after 16 weeks of study drug administration
4) Disposition index after initiation of study drug administration (insulinogenic index at 12 weeks x ISI at 16 weeks)
5)Disposition index after 16 weeks of study drug administration (iAUC IRI0-10 x ISI)
6)Liver insulin sensitivity after 16 weeks of study drug administration: Liver glucose uptake/oral glucose load
7)iAUC IRI at Clamp OGL after 16 weeks of study drug administration
8)Absolute values and changes in lipid profiles (T-chol, TG, HDL-C, LDL-C, FFA) from the start of study drug administration to 16 weeks after the start of study drug administration
9) Absolute values and changes in adiponectin from the start of study drug administration to 16 weeks after the start of study drug administration
10) Absolute values and changes in body weight, body fat mass, body fat percentage, and muscle mass from the start of study drug administration to 16 weeks after the start of study drug administration
11)Oxidative/non-oxidative glucose disposal and metabolic flexibility measured by indirect calorimetry after 16 weeks of treatment with the study drug
12)Glucose effectiveness (model analysis using 75g OGTT and glucose clamp time series data)
13)Change in SgIo from the start of study drug administration to 12 weeks after the start of study drug administration
14)Change in glucagon-related indices (AUC GCG120, deltaGCG 0-30, GCG suppression rate 0-30, GCG suppression rate 0-120, and GCG suppression rate 30-120) from the start of study drug administration to 12 weeks post-dose ) changes in the amount of
15) Fasting CPR index and Fasting Glucagon/insulin index at the start of study drug administration, 12 weeks after the start of study drug administration, and 16 weeks after the start of study drug administration
Fasting CPR index = CPR / BG x 100
Fasting Glucagon/insulin index = glucagon / BG x 100

<Safety evaluation items>
1)Frequency and rate of adverse events

<Exploratory endpoints>
1)Changes in the composition and function of the intestinal microbiota from baseline to 12 weeks after drug administration
2)Changes in metabolites in feces and plasma (metabolomic analysis) from baseline to 12 weeks afte r drug administration
3)Change in Bristol stool scale from baseline to 12 weeks after drug administration

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 75age old
• Gender: Both

Include criteria

(1)Patients between 20 and 75 years old
(2)Patients diagnosed with type 2 diabetes mellitus
(3)BMI of the patients more than 18.5 kg/m2
(4)Patients who have been taking only diet and ex ercise therapy or only dipeptidyl peptidase 4 (DPP 4) inhibitors without changing the dosage and ad ministration for the treatment of diabetes for at least 8 weeks prior to obtaining consent
(5)Patients whose HbA1c is less than 9.5 % at the time of eligibility test
(6)Patients who have given their free and written consent to participate in this clinical research

Exclude criteria

(1)Patients using insulin, GLP-1RA, or oral hypoglycemic agents other than DPP4 inhibitors
(2)Patients with severe hepatic dysfunction (AST/ALT greater than 4 times the upper limit of normal)
(3)Patients with renal dysfunction (eGFR less than 45 mL/min/1.73m2)
(4)Patients who have undergone gastrectomy (not including endoscopic mucosal resection)
(5)Patients with proliferative diabetic retinopathy ( except for patients with obsolete proliferative diabetic retinopathy that does not require treatment)
(6)Patients with severe diabetic neuropathy (patients whose symptoms are so severe that they seriously interfere with daily life and require assistance)
(7)Patients with a cardiac function classification of grade 3 or 4 according to NYHA at an evaluation within the last year
(8)Patients who drink excessively and habitually
(9)Patients with a history of lactic acidosis
(10)Patients with a history of severe ketosis, diabetic coma, or precoma
(11)Patients who have undergone major surgery within one month
(12)Patients with severe infection or serious trauma
(13)Patients with malignant tumors under treatment or within 5 years of completion of treatment
(14)Pregnant women, lactating women, and patients who may be or are planning to become pregnant
(15)Patients who have used antibiotics or antiparasitic drugs within one month prior to eligibility confirmation
(16)Patients who have taken PPI (proton pump inhibitor), steroids, or immunosuppressive drugs within one month prior to eligibility confirmation
(17)Patients with lower gastrointestinal diseases ( Crohn's disease, ulcerative colitis, short bowel syndrome, celiac disease, etc.)
(18)Patients who are participating in clinical research involving other interventions(However, participation in the "Study to evaluate intestinal FDG accumulation on 18F-FDG-PET/MRI in patients taking imegurimine or metformin" is acceptable)
(19)Patients who are judged by the principal investigator or sub-investigator to be inappropriate for this clinical research

Related Information

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