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

Official title

Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease

Overview

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.

Interventions

• Drug Tofogliflozin
  Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.
• Drug Metformin
  Metformin is started at 500 mg daily and orally administered in 2 to 3 divided doses immediately before or after meals. The dose during the maintenance period is determined by observing the effect, but is usually 750 to 1,500 mg daily. Metformin is orally administered for 104 weeks throughout post-start period. The dose may be adjusted according to the patient's condition, but the maximum daily dose should be 2,250 mg.

Primary outcome measures

• Urine albumin-to-creatinine ratio (UACR) [Time frame: Up to 52 weeks]

Secondary outcome measures (12)

• Urine albumin-to-creatinine ratio (UACR) [Time frame: Up to 26 and 104 weeks]
• Urine albumin-to-creatinine ratio (UACR) [Time frame: Up to 26, 52 and 104 weeks]
• Change slope in eGFR [Time frame: Up to 52 and 104 weeks]
• HbA1c [Time frame: Up to 52 and 104 weeks]
• Body weight [Time frame: Up to 52 and 104 weeks]
• Systolic / diastolic blood pressure [Time frame: Up to 52 and 104 weeks]
• Total serum proteins [Time frame: Up to 52 and 104 weeks]
• Serum albumin [Time frame: Up to 52 and 104 weeks]
• Uric acid [Time frame: Up to 52 and 104 weeks]
• Hematocrit [Time frame: Up to 52 and 104 weeks]
• Hemoglobin [Time frame: Up to 52 and 104 weeks]
• Red blood cell count [Time frame: Up to 52 and 104 weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Japan · 1 center

• Shinshu University — Matsumoto

Publications

• Kimura K, Takagi Y, Harada M, Ueda S, Minamisawa M, Sonoda K, Oiwa A, Yazaki Y, Sakurai S, Tomita T, Kaneko K, Yamamoto K, Takama N, Momose S, Inobe Y, Nogi K, Koshikawa M, Misawa T, Kasai T, Tsutsui H, Watanabe N, Yamazaki K, Miyamoto T, Midorikawa T, Usui T, Saigusa T, Motoki H, Saito Y, Kamijo Y, Komatsu M, Kuwahara K. Effect of Tofogliflozin on Urinary Albumin-to-Creatinine Ratio vs. Metformin PMID 41252113
• El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2. PMID 38837240

Identifiers

NCT: NCT05469659 · 21-02 · jRCTs031210339

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗