New Study Backs SGLT2 Inhibitors for Kidney Health in High-Risk Diabetes Cases: Study

The findings, published in Diabetes, Obesity and Metabolism, suggest that SGLT2 inhibitors slowed kidney function decline by 21% (HR 0.79) in insulin-deficient diabetes patients over 4.5 years. Users also had a lower risk of serum creatinine doubling (HR 0.76) and showed improvements in albuminuria, with 51% achieving normoalbuminuria. Although the risk of diabetic ketoacidosis was slightly higher (2.81% vs. 2.19%), the overall incidence remained low, reinforcing the renal benefits of SGLT2 inhibitors.

Chronic kidney disease (CKD) is a serious complication of diabetes, often progressing to diabetic kidney disease (DKD) and increasing the risk of kidney failure. While SGLT2 inhibitors are known for their cardiovascular and renal benefits in type 2 diabetes, their effectiveness in insulin-deficient patients remains uncertain. Given the high risk of DKD in this population, understanding the kidney-protective effects of these medications is crucial. However, limited data exist on their impact, emphasizing the need for further research to explore their potential benefits and optimize treatment strategies for high-risk patients.

To fill this knowledge gap, Anat Tsur MD, Department of Endocrinology and Metabolism, Clalit Health Services, Jerusalem, Israel, and colleagues aimed to examine the effect of SGLT2 inhibitors on kidney outcomes in insulin-deficient diabetes patients using real-world data.

For this purpose, the researchers conducted a retrospective cohort study using data from a large Health Maintenance Organization in Israel. They analyzed 12,530 propensity score-matched adults with insulin-deficient diabetes, categorizing them into SGLT2i users and non-users, with a median follow-up of 1,657 days. The primary outcome was a composite measure of a ≥50% decline in eGFR to <60 mL/min/1.73 m² or progression to eGFR <15 mL/min/1.73 m². Secondary outcomes included serum creatinine doubling and changes in albuminuria status.

The study revealed the following findings:

• SGLT2 inhibitor use linked to a lower incidence of the primary outcome (6.1% vs. 7.5%; HR 0.79).
• Secondary analysis showed a significant reduction in serum creatinine doubling (HR 0.76).
• Albuminuria improved in SGLT2i users, with 51% transitioning to normoalbuminuria.
• The benefits remained consistent across different patient subgroups.
• Diabetic ketoacidosis (DKA) incidence was slightly higher in SGLT2i users (2.81% vs. 2.19%), but overall occurrence was low.

This study provides strong evidence that SGLT2 inhibitors offer significant kidney protection in insulin-deficient patients, extending benefits beyond type 2 diabetes. The consistent improvements in albuminuria and slower eGFR decline suggest their potential as a valuable treatment option for high-risk populations. However, the slightly increased risk of diabetic ketoacidosis highlights the need for careful monitoring and patient education.

"These findings address a critical gap in diabetes management, emphasizing the importance of further large-scale trials to validate their role in reducing the burden of diabetic kidney disease in insulin-deficient individuals," the authors concluded.

Reference:

Tsur A, Cahn A, Hanoch L, Pollack R. Kidney outcomes with SGLT2 inhibitors in patients with diabetes and an insulin-deficient phenotype: A real world analysis. Diabetes Obes Metab. 2025 Mar 14. doi: 10.1111/dom.16329. Epub ahead of print. PMID: 40084557.