Long-term Use of Empagliflozin, SGLT2 Inhibition Associated With Mitigation of Kidney Function Loss

A poster presented at Kidney Week 2022 found that long-term use of empagliflozin (EMPA) or any sodium-glucose cotransporter 2 (SGLT2) inhibitors was associated with mitigation of kidney function loss in patients with type 2 diabetes (T2D) compared with patients who took dipeptidyl peptidase-4 (DPP4) inhibitors.

SGLT2 inhibitors have been shown to mitigate kidney function loss in patients with T2D when tested in randomized controlled studies. However, their long-term effects have not been tested and was therefore the primary aim of this study.

The Maccabi Healthcare Services database, an Israeli database with data from 2015 to 2021, was used for this study. The change in estimated glomerular filtration rate (eGFR) in patients with T2D who started EMPA or any SGLT2 inhibitor was compared with patients using DPP4 inhibitors. All treatment arms were score-matched based on 96 baseline characteristics.

Participants were followed until death, end of available data, exposure discontinuation, initiation of the comparator drug, after 5 years, or until October 2021. Exposure periods were used to differentiate when medical treatment had been started. The "intention to treat” analysis had a follow-up that continued until death or the end of available data and an “as treated” analysis had a follow-up that was censured as drug discontinuation or starting a comparator drug. The “as treated” analysis definition comprised a supply period and a grace period of 90 days after the end of the drug supply.

Patients were included if they received at least 1 package of EMPA, any SGLT2 inhibitor, or any DPP4 inhibitor during the study period; received a T2D diagnosis before the index date; and had at least 1 eGFR measurement in the year prior to the index date. Patients were excluded if they were younger than 18 years, had type 1 diabetes, had a record of SGLT2 or DPP4 inhibitor use in the previous year, were prescribed SGLT2 and DPP4 inhibitors on the index date, had an indication of dialysis or kidney transplantation, had less than 12 months of available data, or were pregnant.

There were 15992 participants who had started EMPA or DPP4 inhibitors, and they were matched in a 1:1 ratio. There were 12781 participants (79.9%) who had an eGFR measurement recorded at the follow-up. The median (IQR) follow up was 17.9 (9.5-33.5) months, and 4924 participants (38.5%) were followed for 2 years or more.

The study found that the mean eGFR slope was less steep in participants with EMPA vs those on DPP4i (–1.33 vs –2.26 mL/min/1.73 m² per year respectively). The mean absolute between-arms difference favored EMPA by 0.93 mL/min/1.73 m² per year (95% CI, 0.67-1.18). The mitigation of the eGFR slope increased with EMPA with longer treatment. When comparing initiators of SGLT2 inhibitors with DPP4 inhibitors, similar significant effects were obtained.

The researchers concluded that SGLT2 inhibitors and EMPA were effective in mitigating kidney function loss when taken long term compared with DPP4 inhibitors. Further, these benefits apply to patients with T2D and to patients in different subgroups, including those without cardiovascular or kidney disease.

Reference

Mosenzon O, Cohen CM, Yanuv I, et al. Long-term use of empagliflozin vs. DPP4 inhibitors mitigates eGFR slopes in patients with type 2 diabetes: real-world evidence. Presented at: Kidney Week 2022; November 3-6, 2022; Orlando, FL. Abstract SA-PO266.