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

NCT05469659 | Recruiting Phase 2 DMC

• 2 other identifiers: 21-02jRCTs031210339
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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).

Conditions

T2DM (Type 2 Diabetes Mellitus); Metformin; SGLT2-Inhibitors

Outcome Measures

Primary Outcomes (1)

• Urine albumin-to-creatinine ratio (UACR)

  Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.

  Up to 52 weeks

Secondary Outcomes (17)

• Urine albumin-to-creatinine ratio (UACR)

  Up to 26 and 104 weeks

• Urine albumin-to-creatinine ratio (UACR)

  Up to 26, 52 and 104 weeks

• Change slope in eGFR

  Up to 52 and 104 weeks

• HbA1c

  Up to 52 and 104 weeks

• Body weight

  Up to 52 and 104 weeks

Study Arms (2)

Tofogliflozin

EXPERIMENTAL

Drug: Tofogliflozin

Metformin

ACTIVE COMPARATOR

Drug: Metformin

Interventions

Tofogliflozin DRUG

Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.

Tofogliflozin

Metformin DRUG

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.

Metformin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shinshu University: lead
• Kowa Company, Ltd.: collaborator

Study Sites (1)

Shinshu University

Matsumoto, Nagano, 390-8621, Japan

RECRUITING

Related Publications (2)

• 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 in Diabetic Kidney Disease: Rationale and Study Protocol of the TRUTH-DKD Trial. Diabetes Ther. 2025 Nov 18. doi: 10.1007/s13300-025-01822-8. Online ahead of print.

  PMID: 41252113 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

6-((4-ethylphenyl)methyl)-3',4',5',6'-tetrahydro-6'-(hydroxymethyl)spiro(isobenzofuran-1(3H),2'-(2H)pyran)-3',4',5'-triol; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Koichiro Kuwahara, MD, PhD

  Shinshu University School of Medicine

  STUDY CHAIR

Central Study Contacts

Koichiro Kuwahara, MD, PhD

CONTACT

+81-263-37-3191; kkuwah@shinshu-u.ac.jp

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 22, 2022
• Study Start: September 22, 2021
• Primary Completion: October 30, 2025
• Study Completion (Estimated): October 30, 2026
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

JP (1)