T2DM (Type 2 Diabetes Mellitus)Phase 2TRUTH-DKDNCT05469659
Effect of Tofogliflozin on UACR Compared to Metformin Hydrochloride in Diabetic Kidney Disease (TRUTH-DKD)
A Phase 2 study testing Tofogliflozin and Metformin in people with T2DM (Type 2 Diabetes Mellitus) and Metformin, run by Shinshu University at 1 site in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- T2DM (Type 2 Diabetes Mellitus), Metformin, SGLT2-Inhibitors
- What is being tested?
- Tofogliflozin and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteJapan
- Study dates
- 22 Sep 2021to 30 Oct 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Japan1 site, 1 recruiting
- Recruiting
Shinshu University
Matsumoto, Nagano, 390-8621
Koichiro Kuwahara, MD, PhD, +81-263-37-3191, kkuwah@shinshu-u.ac.jp
Masatoshi Minamisawa, +81-263-37-3191, nanchan7131@gmail.com
About this study
Official title: Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease
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).
Read the 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.
- Conditions
- T2DM (Type 2 Diabetes Mellitus), Metformin, SGLT2-Inhibitors
- Being tested
- Tofogliflozin, Metformin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TofogliflozinDrug
Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.
MetforminDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Tofogliflozin | Experimental | Not described Receives: Drug: Tofogliflozin |
| Metformin | Active comparator | Not described Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urine albumin-to-creatinine ratio (UACR)
Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.
Measured: Up to 52 weeks
Secondary outcomes (17)
Urine albumin-to-creatinine ratio (UACR)
Change from baseline in urine albumin-to-creatinine ratio (UACR) after 26 and 104 weeks treatment.
Measured: Up to 26 and 104 weeks
Urine albumin-to-creatinine ratio (UACR)
Change rates from baseline in urine albumin-to-creatinine ratio (UACR) after 26, 52 and 104weeks treatment.
Measured: Up to 26, 52 and 104 weeks
Change slope in eGFR
Change slope in eGFR
Measured: Up to 52 and 104 weeks
HbA1c
Change in HbA1c
Measured: Up to 52 and 104 weeks
Body weight
Changes in body weight
Measured: Up to 52 and 104 weeks
Systolic / diastolic blood pressure
Changes in systolic / diastolic blood pressure
Measured: Up to 52 and 104 weeks
Total serum proteins
Changes in total serum proteins
Measured: Up to 52 and 104 weeks
Serum albumin
Changes in serum albumin
Measured: Up to 52 and 104 weeks
Uric acid
Changes in uric acid
Measured: Up to 52 and 104 weeks
Hematocrit
Changes in hematocrit
Measured: Up to 52 and 104 weeks
Hemoglobin
Changes in hemoglobin
Measured: Up to 52 and 104 weeks
Red blood cell count
Changes in red blood cell count
Measured: Up to 52 and 104 weeks
Pulse rate
Changes in pulse rate
Measured: Up to 52 and 104 weeks
Triglyceride
Changes in triglyceride
Measured: Up to 52 and 104 weeks
Low-density lipoprotein
Changes in low-density lipoprotein
Measured: Up to 52 and 104 weeks
High-density lipoprotein
Changes in high-density lipoprotein
Measured: Up to 52 and 104 weeks
Albuminuria class
Transition of albuminuria class
Measured: Up to 104 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2022
- Study start22 Sep 2021
- Primary completion30 Oct 2025 (estimated)
- Study completion30 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for T2DM (Type 2 Diabetes Mellitus)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shinshu University
- Sponsor type
- University, hospital or other
- Collaborators
- Kowa Company, Ltd.
- Responsible party
- Principal investigator, Koichiro Kuwahara, Shinshu University
- Investigators
- Koichiro Kuwahara, MD, PhD, Study chair, Shinshu University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05469659
- Sponsor's protocol ID
- 21-02
- Other IDs
- jRCTs031210339
- Acronym
- TRUTH-DKD
- Status last verified
- Jul 2022
- First submitted
- 15 Jul 2022
- Last updated
- 22 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 in Diabetic Kidney Disease: Rationale and Study Protocol of the TRUTH-DKD Trial. Diabetes Ther. 2026 Jan;17(1):149-163. doi: 10.1007/s13300-025-01822-8. Epub 2025 Nov 18.
PubMed 41252113El-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.
PubMed 38837240
Study at a glance
From the registry record, last updated by the sponsor on 22 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Tofogliflozin on Urine Albumin-to-Creatinine Ratio Compared to Metformin Hydrochloride in Diabetic Kidney Disease
- ClinicalTrials.gov ID
- NCT05469659
- Acronym / sponsor ID
- TRUTH-DKD / 21-02
- Conditions
- T2DM (Type 2 Diabetes Mellitus), Metformin, SGLT2-Inhibitors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Shinshu UniversityUniversity, hospital or other
- Collaborators
- Kowa Company, Ltd.
- Study start
- 22 Sep 2021 (actual)
- Primary completion
- 30 Oct 2025 (estimated)
- Study completion
- 30 Oct 2026 (estimated)
- First posted
- 22 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tofogliflozin | Experimental | Drug: Tofogliflozin |
| Metformin | Active comparator | Drug: Metformin |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TofogliflozinTofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast. | Drug | Tofogliflozin |
| MetforminMetformin 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. | Drug | Metformin |
Primary outcome
Urine albumin-to-creatinine ratio (UACR)
Time frame: Up to 52 weeks
Change from baseline in urine albumin-to-creatinine ratio (UACR) after 52 weeks treatment.
17 secondary outcomes
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
Pulse rate
Time frame: Up to 52 and 104 weeks
Triglyceride
Time frame: Up to 52 and 104 weeks
Low-density lipoprotein
Time frame: Up to 52 and 104 weeks
High-density lipoprotein
Time frame: Up to 52 and 104 weeks
Albuminuria class
Time frame: Up to 104 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jul 2022.
- Derived from this study: PubMed 41252113Kimura 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. 2026 Jan;17(1):149-163. doi: 10.1007/s13300-025-01822-8. Epub 2025 Nov 18.
- Derived from this study: PubMed 38837240El-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Koichiro Kuwahara, MD, PhD study chair
Shinshu University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tofogliflozin and Metformin in people with T2DM (Type 2 Diabetes Mellitus) and Metformin, run by Shinshu University at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Koichiro Kuwahara, MD, PhD (+81-263-37-3191, kkuwah@shinshu-u.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Urine albumin-to-creatinine ratio (UACR) (time frame: Up to 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05469659, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2022.