Effect of Tofogliflozin on UACR Compared to Metformin Hydrochloride in Diabetic Kidney Disease (TRUTH-DKD)

Phase 2

Recruiting

Brief Summary: This multicenter, randomized, open-label, controlled study will assess the efficacy of the SGLT2 inhibitor tofogliflozin on Urine Albumin-to-Creatinine Ratio (UACR) compared to metformin in patients with type 2 diabetes with chronic kidney disease (CKD).

Detailed Description: Eligible participants will be randomly assigned (1:1) to tofogliflozin or metformin with stratification based on UACR (\<300 mg/gCr，≧300mg/gCr), an estimated glomerular filtration rate (eGFR) (\<60mL/min/1.73m2, ≧60 mL/min/1.73m2), and age (\<65 years old, ≧65 years old). The primary end point is change in urine albumin-to-creatinine ratio (UACR) from baseline after 52 weeks treatment. Changes in eGFR, HbA1c, body weight, systolic blood pressure, diastolic blood pressure, total serum proteins, serum albumin, uric acid, hematocrit, hemoglobin, red blood cell count, pulse rate, triglyceride, low-density lipoprotein, high-density lipoprotein and albuminuria class transition rate will also be evaluated.

Recruitment & Eligibility

Inclusion Criteria

Type 2 diabetic patients
Patients aged 20 years or older at the time of obtaining consent
Patients with HbA1c 6.5 or more and 9.0% or less within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)
Patients who have been judged by their doctor to need a diabetic drug when they are first seen, or who have already taken a diabetic drug and have decided that it is necessary to add one diabetic drug.
Patients who have been receiving RAS inhibitors (ARB, ARNI, ACE inhibitors, direct renin inhibitors) for 4 weeks or longer
Patients with eGFR of 30 or more (mL / min / 1.73m2) within 13 weeks before obtaining consent (evaluated by test values after 4 weeks or more without taking SGLT2 inhibitor / metformin)
Patients with urinary albumin / creatinine ratio (UACR) of 30 or more and less than 2000 (mg / gCr) (4 weeks or more without taking SGLT2 inhibitor / metformin) within 13 weeks before obtaining consent Evaluate by inspection value)
Patients for whom written consent was obtained based on the patient's free will after receiving sufficient explanation for participation in this study

Exclusion Criteria

Patients receiving treatment with SGLT2 inhibitor or metformin within 13 weeks before obtaining consent
Dialysis patient
Patients with a history of severe hypoglycemia
Patients with hypersensitivity to SGLT2 inhibitor or metformin
Pregnant women, lactating patients, and patients who wish to raise children
Patients with BMI of 35 kg / m2 or more based on the latest measured values within 13 weeks before obtaining consent
Patients who are contraindicated for the study drug
Other patients who the attending physician deems inappropriate as a subject

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	-
Tofogliflozin	Tofogliflozin	-

Primary Outcome Measures

Name	Time	Method
Urine albumin-to-creatinine ratio (UACR)	Up to 52 weeks	Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.

Secondary Outcome Measures

Name	Time	Method
Change slope in eGFR	Up to 52 and 104 weeks	Change slope in eGFR
HbA1c	Up to 52 and 104 weeks	Change in HbA1c
Body weight	Up to 52 and 104 weeks	Changes in body weight
Total serum proteins	Up to 52 and 104 weeks	Changes in total serum proteins
Serum albumin	Up to 52 and 104 weeks	Changes in serum albumin
Systolic / diastolic blood pressure	Up to 52 and 104 weeks	Changes in systolic / diastolic blood pressure
Uric acid	Up to 52 and 104 weeks	Changes in uric acid
Urine albumin-to-creatinine ratio (UACR)	Up to 26, 52 and 104 weeks	Change rates from baseline in urine albumin-to-creatinine ratio (UACR) after 26, 52 and 104weeks treatment.
Hematocrit	Up to 52 and 104 weeks	Changes in hematocrit
Hemoglobin	Up to 52 and 104 weeks	Changes in hemoglobin
Red blood cell count	Up to 52 and 104 weeks	Changes in red blood cell count
Pulse rate	Up to 52 and 104 weeks	Changes in pulse rate
Triglyceride	Up to 52 and 104 weeks	Changes in triglyceride
Low-density lipoprotein	Up to 52 and 104 weeks	Changes in low-density lipoprotein
High-density lipoprotein	Up to 52 and 104 weeks	Changes in high-density lipoprotein
Albuminuria class	Up to 104 weeks	Transition of albuminuria class