Metformin, SGLT2-Inhibitors, T2DM (Type 2 Diabetes Mellitus)
Conditions
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.
Interventions
DRUGTofogliflozin
Tofogliflozin 20 mg is orally administered once daily for 104 weeks before or after breakfast.
DRUGMetformin
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.
Sponsors
Kowa Company, Ltd.
Shinshu University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Systolic / diastolic blood pressure | Up to 52 and 104 weeks | Changes in systolic / diastolic blood pressure |
| 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 |
| Uric acid | Up to 52 and 104 weeks | Changes in uric acid |
| Urine albumin-to-creatinine ratio (UACR) | Up to 26 and 104 weeks | Change from baseline in urine albumin-to-creatinine ratio (UACR) after 26 and 104 weeks treatment. |
| 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 |
| Hematocrit | Up to 52 and 104 weeks | Changes in hematocrit |
Countries
Japan
Contacts
Primary ContactKoichiro Kuwahara, MD, PhD
Outcome results
None listed