Study on the effectiveness of SGLT2 inhibitor, Tofogliflozin, AND Biguanide, metformin for tYpe 2 diabetic patients with NonAlcoholic Fatty Liver Disease

JRCT ID: jRCTs031190040

Registered date:17/06/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus
• Date of first enrollment: 09/10/2019
• Target sample size: 40
• Study type: Interventional

Intervention(s)

Arm A
<Time Frame 0 to 24 weeks>
Tofogliflozin 20mg/day
<Time Frame 24 to 48 weeks>
Tofogliflozin 20mg/day + Metformin 1500mg/day

Arm B
<Time Frame 0 to 4-8 weeks>
Metformin 500mg/day
<Time Frame 4-8 to 24 weeks>
Metformin 1500mg/day
<Time Frame 24 to 48 weeks>*
Tofogliflozin 20mg/day + Metformin 1500mg/day

Outcome(s)

• Primary Outcome: Change in liver fat content as measured by MRI-PDFF( proton density fat fraction). <Time frame: 24 weeks, comparison of arm A and B>

Secondary Outcome

Important secondary endpoint
Change in liver stiffness as measured by MR elastography. <Time frame: 24 weeks, comparison of arm A and B>

Secondary endpoint
1.% change of liver fat content as measured by MRI-PDFF. <Time frame: 24 weeks, comparison of arm A and B>
2.Change in, and % change of liver fat content as measured by MRI-PDFF. <Time frame: 24 weeks, comparison of before and after >
3.Change in, and % change of liver fat content as measured by MRI-PDFF. <Time frame: 48 weeks, comparison of arm A and B, and before and after >
4.% Change of liver stiffness as measured by MR elastography. <Time frame: 24 weeks, comparison of arm A and B>
5.Change in, and % Change of liver stiffness as measured by MR elastography. <Time frame: 24 weeks, comparison of before and after >
6.Change in, and % change of liver stiffness as measured by MR elastography. <Time frame: 48 weeks, comparison of arm A and B, and before and after >
7.Change in, and % change of following parameters. <Time frame: 24, and 48 weeks, comparison of arm A and B, and before and after >
8.Change in, and % change of following parameters from 24 to 48 weeks. <Comparison of week 24 and 48, and arm A and B >
9.Incidence of adverse events

<Parameters>
ALT, AST, gamma-GTP, PT, TP, Alb, ChE, type IV collagen 7S, P-III-P, hyaluronic acid
Body weight, body mass index, west circumference, blood pressure
HbA1c, fasting blood glucose, glycoalbumin, insulin, HOMA-R, CPI
TC, HDL-C, LDL-C, TG, RLP-C
Serum creatinine, eGFR
White blood cell, red blood cell, hemoglobin, hematocrit, platelet
Total ketone, beta-hydroxybutyric acid, acetoacetic acid
Uric acid
BUN, Na, K, P, Ca, Mg, Fe, ferritin, bilirubin fraction
Urine sugar, urinary ketone body, urinary albumin
Visceral fat area
Fat accumulation content of intrahepatic
Body fat mass, fat-free mass, muscle mass <Arbitrary parameters>

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Type 2 diabetic patients who satisfy all the following criteria
1.Clinically diagnosed with NAFLD / NASH(within 3 years before informed consent)
2.6.5% < HbA1c < 10.0%
3.8 % < MRI-PDFF(within 12 weeks before informed consent)
4.Patients who can take metformin and tofogliflozin
5.20 years < age
6.Written informed consent

Exclude criteria

1.Type 1 diabetes or gestational diabetes
2.Use of SGLT2 inhibitor within 12 weeks before informed consent
3.Use of biguanide within 12 weeks before informed consent
4.Use of GLP-1 receptor agonist within 12 weeks before informed consent
5.Use of Thiazolidine within 12 weeks before informed consent
6.Use of Vitamin E preparation within 12 weeks before informed consent
7.Contraindication to tofogliflozin and metformin
8.Hypersensitivity to tofogliflozin and metformin
9.Absolute indications for insulin treatment
10.History of hypoglycemia with loss of consciousness
11.eGFR < 30mL/min/1.73m2
12.Serious liver functional impairment(Child-Pugh classification B or C)
13.History of cancer or high possibility of cancer recurrence
14.Pregnant, or possibly pregnant, nursing
15.Other ineligibility determined by an investigator

Related Information

• Primary Sponsor: Yumi Takiyama
• Source(s) of Monetary Support: Kowa Company, Ltd.