Comparison of SGLT2 Inhibitors for New-Onset Proteinuria Risk in Patients With Type 2 Diabetes and Preserved Kidney...

Area of Science:

• Nephrology
• Endocrinology
• Pharmacology

Background:

• Type 2 diabetes is a leading cause of chronic kidney disease.
• Sodium-glucose cotransporter-2 (SGLT2) inhibitors are used to manage type 2 diabetes and have shown kidney-protective effects.
• New-onset proteinuria is a marker of kidney damage.

Purpose of the Study:

• To compare the effectiveness of individual SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) in preventing new-onset proteinuria.
• To assess the risk of new-onset proteinuria in patients with type 2 diabetes and preserved kidney function treated with different SGLT2 inhibitors.

Main Methods:

• A target trial emulation using health checkup and claims data from April 2014 to March 2023.
• Inclusion criteria: type 2 diabetes with HbA1c ≥6.5% and preserved kidney function (eGFR ≥60 mL/min/1.73 m², urinary protein <1+).
• Inverse probability of treatment and censoring weighting were used to adjust for confounders and loss to follow-up.

Main Results:

• The study included patients with a mean age of 67.5 years, 60% male, mean HbA1c of 7.56%, and mean eGFR of 75.0 mL/min/1.73 m².
• During a median follow-up of 522 days, new-onset proteinuria occurred in 43 (empagliflozin), 66 (dapagliflozin), and 48 (canagliflozin) users.
• Dapagliflozin showed a significantly higher risk of new-onset proteinuria (HR 1.64) compared to empagliflozin, particularly in men (HR 2.34).

Conclusions:

• Empagliflozin was associated with a lower risk of new-onset proteinuria compared to dapagliflozin in patients with type 2 diabetes and preserved kidney function.
• These findings suggest that individual SGLT2 inhibitor selection may be important for optimizing kidney protection.
• Further confirmation in randomized controlled trials is warranted.