# Impact of Albuminuria and Renal Dysfunction on the Anemia-Improving Effect of SGLT2 Inhibitors in Patients With Type 2 Diabetes: A Real-World Observational Study

## TL;DR

This study finds that high levels of albuminuria reduce the effectiveness of SGLT2 inhibitors in improving anemia in patients with type 2 diabetes.

## Contribution

The study reveals that severe albuminuria, but not eGFR, diminishes the anemia-improving effect of SGLT2 inhibitors in T2D patients.

## Key findings

- Patients with macroalbuminuria showed a significantly smaller increase in hemoglobin after SGLT2 inhibitor treatment.
- Nephrotic-range proteinuria was associated with no hemoglobin increase from SGLT2 inhibitors.
- Baseline eGFR was not significantly associated with changes in hemoglobin levels.

## Abstract

Aim: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been reported to increase hemoglobin levels; however, little is known about the magnitude of their anemia-improving effect in patients with advanced chronic kidney disease. We aimed to determine the influence of albuminuria and renal dysfunction on the anemia-improving effects of SGLT2 inhibitors in patients with Type 2 diabetes (T2D).

Materials and Methods: In this clinically based retrospective longitudinal study, the records of 4664 consecutive patients with T2D were reviewed. We investigated the effects of albuminuria and eGFR at baseline on change in hemoglobin after 3 months of SGLT2 inhibitor treatment by a multivariable linear regression analysis with calculation of the unstandardized partial regression coefficient (B).

Results: Among the patients with T2D, 230 patients (male, n = 170; female, n = 60; age, 67.0 ± 11.5 years) were eligible for the analysis. Patients with macroalbuminuria (urine albumin-to-creatinine ratio (uACR) > 300 mg/g or urine protein-to-creatinine ratio (uPCR) > 500 mg/g) exhibited a significantly smaller increase in hemoglobin after the initiation of SGLT2 inhibitor treatment (B −5.923 g/L, p = 0.003) compared to patients with normoalbuminuria (uACR < 30 mg/g or uPCR < 150 mg/g). Furthermore, almost all patients with proteinuria in the “nephrotic range,” defined as uPCR > 3500 mg/g, did not experience increased hemoglobin from SGLT2 inhibitor treatment. However, we could not find a significant association between the eGFR at baseline (including eGFR ≤ 15 mL/min/1.73 m2) and change in hemoglobin with SGLT2 inhibitor treatment.

Conclusions: Our findings indicate that severely increased albuminuria attenuates the anemia-improving effect of SGLT2 inhibitors for at least 3 months after their administration.