# The effect of empagliflozin on renal outcomes compared to sitagliptin with type 2 diabetes: target trial emulation using electronic medical records

## TL;DR

This study compares empagliflozin and sitagliptin in type 2 diabetes patients, finding that empagliflozin may better protect kidney function but raises serum phosphorus levels.

## Contribution

The study uses real-world electronic medical records to evaluate empagliflozin's renal benefits compared to sitagliptin in a Korean population.

## Key findings

- Empagliflozin was associated with a slower decline in eGFR compared to sitagliptin.
- Empagliflozin led to increased serum phosphorus levels and greater weight loss.
- Serum uric acid levels decreased more in the empagliflozin group.

## Abstract

The renal effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors in diverse populations remain under investigation. While randomized controlled trials have shown renoprotective effects of SGLT2 inhibitors, their impact in routine clinical settings and specific populations such as Koreans requires further evaluation.

This study aimed to evaluate the impact of empagliflozin compared to sitagliptin on renal function and related clinical outcomes in patients with type 2 diabetes (T2D) using a target trial emulation approach.

We conducted a retrospective cohort study using electronic medical records from a Korean tertiary care hospital between 2018 and 2019. New users of empagliflozin or sitagliptin were identified and matched using propensity scores to control for confounding factors. Primary outcomes included changes in estimated glomerular filtration rate (eGFR) and other renal function markers over time. Secondary outcomes included acute kidney injury, albuminuria, and composite renal events, as well as other clinical parameters. A modified intention-to-treat analysis was performed, with follow-up up to 13 months.

After matching, 219 T2D patients were identified in each group. Empagliflozin was associated with a slower decline in eGFR compared to sitagliptin (p < 0.05). Serum phosphorus levels increased more with empagliflozin (p < 0.05). Empagliflozin showed a non-significant trend toward lower risk of composite renal outcomes (hazard ratio [HR] 0.78; 95% confidence interval [CI], 0.50–1.22). Significant increases in weight loss (HR 2.95; 95% CI, 2.01–4.33) and urination frequency (HR 4.05; 95% CI, 1.14–14.34) were observed with empagliflozin. Serum uric acid levels decreased more in the empagliflozin group (p < 0.05).

This real-world study suggests that empagliflozin may offer renoprotective benefits compared to sitagliptin in T2D patients. However, the increased serum phosphorus levels warrant careful monitoring. These findings provide valuable insights for clinical decision-making in managing T2D patients at risk of renal complications.

The online version contains supplementary material available at 10.1007/s11096-025-02024-9.