Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria

Afif Nakhleh; Muhammad Abdul-Ghani; Sivan Gazit; Adi Gross; Idit Livnat; Maya Greenbloom; Adva Yarden; Khaled Khazim; Naim Shehadeh; Cheli Melzer Cohen

doi:10.1111/dom.15623

Real-world effectiveness of sodium-glucose cotransporter-2 inhibitors on the progression of chronic kidney disease in patients without diabetes, with and without albuminuria

Diabetes Obes Metab. 2024 Apr 28. doi: 10.1111/dom.15623. Online ahead of print.

Authors

Afif Nakhleh^{1

2

3}, Muhammad Abdul-Ghani^{1

4}, Sivan Gazit⁵, Adi Gross⁶, Idit Livnat⁶, Maya Greenbloom⁶, Adva Yarden⁶, Khaled Khazim¹, Naim Shehadeh^{1

2

3}, Cheli Melzer Cohen⁵

Affiliations

¹ Diabetes and Endocrinology Clinic, Maccabi Healthcare Services, Haifa, Israel.
² Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel.
³ Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
⁴ Division of Diabetes, University of Texas Health Science Centre, San Antonio, Texas, USA.
⁵ Maccabi Institute for Research and Innovation, Tel-Aviv, Israel.
⁶ Medical Affairs, AstraZeneca, Kfar Saba, Israel.

PMID: 38680053
DOI: 10.1111/dom.15623

Abstract

Aim: To examine the renal effects of sodium-glucose cotransporter-2 (SGLT2) inhibition among non-diabetic individuals with chronic kidney disease (CKD) in a real-world setting.

Methods: We collected de-identified data on adults without diabetes and with an estimated glomerular filtration rate (eGFR) of 25-60 mL/min/1.73 m², who initiated the SGLT2 inhibitors dapagliflozin or empagliflozin between September 2020 and November 2022 at Maccabi Healthcare Services, an Israeli health maintenance organization. We assessed the effects of SGLT2 inhibitors on renal function (changes in eGFR slope/time). Index date was defined as the date of the first dispensing of SGLT2 inhibitors. Annual baseline slope was calculated using all eGFR measurements during the 2 years prior to index date (median = 7 measurements), while annual follow-up slope was calculated from all evaluations during 90-900 days post index date, along with baseline measurement at index date (median = 6 measurements). Paired t tests were used to compare differences between baseline and follow-up annual slopes.

Results: Of a total of 354 participants with CKD, without diabetes, who received SGLT2 inhibitors and were followed for a median of 527 days, the mean age was 72.8 ± 11.8 years, 26% were female, and 91% used renin-angiotensin system blockade. The mean eGFR was 45.4 ± 9.5 mL/min/1.73 m². The mean body mass index was 29.1 ± 5.4 kg/m². During the year before index date, 146 participants (41%) had a urinary albumin to creatinine ratio (UACR) <30 mg/g, 81 (23%) had a UACR of 30-300 mg/g, 74 (21%) had a UACR >300 mg/g, and 53 (15%) had no UACR evaluation. The mean eGFR slope over time was -5.6 ± 7.7 mL/min/1.73 m² per year at baseline, which improved to -1.7 ± 6.8 mL/min/1.73 m² per year after SGLT2 inhibitor administration (p <0.001). This effect was independent of UACR.

Conclusion: In a real-world study of primarily older non-diabetic adults with CKD, SGLT2 inhibition was associated with a slower rate of kidney function decline, regardless of baseline UACR level.

Keywords: CKD; SGLT2 inhibitors; eGFR slope.

Grants and funding

AstraZeneca