Kidney outcomes with SGLT2 inhibitors in patients with diabetes and an insulin-deficient phenotype: A real world analysis

Abstract

Aim

Diabetic kidney disease (DKD) is a major complication of diabetes, including in insulin-deficient phenotypes, yet data on kidney outcomes with sodium-glucose cotransporter 2 inhibitors (SGLT2i) in this population are limited. This study investigates the impact of SGLT2i on kidney outcomes in patients with insulin-deficient diabetes using real world data.

Materials and Methods

This retrospective cohort study utilized data from a large Health Maintenance Organization in Israel and included 12,530 propensity score-matched adults with insulin-deficient diabetes. Patients were categorized into SGLT2i users and non-users and followed for a median of 1657 days. The primary outcome was a composite of ≥50% decline in eGFR to <60 mL/min/1.73 m² or progression to eGFR <15 mL/min/1.73 m². Secondary outcomes included doubling of serum creatinine and changes in albuminuria category.

Results

SGLT2i use was associated with a reduced incidence of the primary outcome (6.1% vs. 7.5%; HR 0.79, p < 0.001). Secondary analyses revealed significant reductions in serum creatinine doubling (HR 0.76, p < 0.001) and improvements in albuminuria, with 51% of SGLT2i users transitioning to normoalbuminuria. Benefits were consistent across subgroups. Although diabetic ketoacidosis (DKA) incidence was higher among SGLT2i users (2.81% vs. 2.19%, p = 0.03), the overall frequency was low.

Conclusions

SGLT2i demonstrated substantial kidney protection in insulin-deficient patients, extending benefits beyond type 2 diabetes. These findings highlight SGLT2i as a potential therapeutic option for mitigating DKD in high-risk populations.