Japan Trial: SGLT2 Inhibitor vs. Metformin for Kidney Protection

Japanese Researchers Challenge Metformin's Role in Diabetic Kidney Disease

A study from Japan, published in Diabetes Therapy, is putting two widely used diabetes medications head-to-head to find out which one better protects the kidneys. Researchers at Shinshu University School of Medicine in Matsumoto, Japan, have launched the TRUTH-DKD Trial — a carefully designed clinical trial comparing tofogliflozin (an SGLT2 inhibitor) against metformin in patients with type 2 diabetes and early-to-moderate diabetic kidney disease (DKD).

Why This Japanese Study Stands Out

Most large kidney-protection studies have been conducted in North America or Europe, often in populations with different baseline characteristics, healthcare access, and dietary patterns. Japanese researchers tend to study leaner populations with type 2 diabetes compared to typical US cohorts, which can affect how medications perform. Importantly, this trial directly compares SGLT2 inhibitors against metformin — something rarely done in US trials, where the two drugs are often studied independently or used together.

The researchers also point out a critical gap: while metformin has been the go-to first-line diabetes drug for decades, the evidence supporting its ability to protect the kidneys or heart is surprisingly thin and comes from older studies. SGLT2 inhibitors, by contrast, have repeatedly shown kidney and heart benefits in modern, rigorous trials.

What the Trial Measures — In Plain English

The key measurement in this study is the urinary albumin-to-creatinine ratio (UACR) — a urine test that detects tiny amounts of a protein called albumin. When albumin leaks into the urine, it signals kidney stress and blood vessel damage. Think of it as an early warning system for kidney decline.

• Normal UACR: Below 30 mg/g
• Early kidney damage (microalbuminuria): 30–300 mg/g
• More significant damage (macroalbuminuria): Above 300 mg/g

The 120 trial participants all have a UACR between 30 and 2,000 mg/g, meaning they already show signs of kidney stress. Their kidney filtration rate (eGFR) must be at least 30 mL/min/1.73m² — roughly equivalent to moderate chronic kidney disease or better. Participants are randomly assigned to either tofogliflozin or metformin and followed for up to two years.

How This Aligns With US Guidelines

Current American Diabetes Association (ADA) guidelines already recommend SGLT2 inhibitors as preferred agents for type 2 diabetes patients who have chronic kidney disease, heart failure, or cardiovascular disease. This Japanese trial could add direct head-to-head evidence supporting that recommendation — something US guidelines currently lack. If tofogliflozin wins, it strengthens the global case for moving SGLT2 inhibitors earlier in treatment for kidney-at-risk patients.

Note: Tofogliflozin is approved in Japan but not currently available in the US. However, closely related SGLT2 inhibitors — empagliflozin (Jardiance) and dapagliflozin (Farxiga) — are widely used in the US and are expected to behave similarly.

Why This Matters for US Patients

If you have type 2 diabetes and your doctor has mentioned protein in your urine or early kidney disease, this research is directly relevant to you. Diabetic kidney disease affects roughly 1 in 3 Americans with type 2 diabetes, and catching it early — before serious filtration loss occurs — is the window where treatment makes the biggest difference. Monitoring your UACR regularly is a simple, inexpensive step that can guide your treatment decisions.

To support your kidney health between doctor visits, explore the monitoring and wellness tools available at mdsdiabetes.com — designed to help US patients stay on top of the numbers that matter most.

Full Citation

Kimura, Takagi, Harada (2026). 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 Therapy: Research, Treatment and Education of Diabetes and Related Disorders. PMID: 41252113. DOI: 10.1007/s13300-025-01822-8. Country of Origin: Japan. Institution: Department of Cardiovascular Medicine, Shinshu University School of Medicine, Matsumoto, Japan.