Open AccessKidney outcomes using a sustained ≥40% decline in eGFR : A meta‐analysis of SGLT2 inhibitor trials
Author(s) -
Cherney David Z. I.,
DagogoJack Samuel,
McGuire Darren K.,
Cosentino Francesco,
Pratley Richard,
Shih Weichung J.,
Frederich Robert,
Maldonado Mario,
Liu Jie,
Wang Shuai,
Can Christopher P.
Publication year - 2021
Publication title -
clinical cardiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.263
H-Index - 72
eISSN - 1932-8737
pISSN - 0160-9289
DOI - 10.1002/clc.23665
Subject(s) - medicine , kidney disease , dialysis , renal function , type 2 diabetes , diabetes mellitus , randomized controlled trial , kidney transplantation , clinical trial , clinical endpoint , kidney , meta analysis , endocrinology
Background A recent meta‐analysis of sodium–glucose cotransporter 2 (SGLT2) inhibitor outcome trials reported that SGLT2 inhibitors were associated with reduction in the risk of adverse composite kidney outcomes, with moderate heterogeneity across the trials; however, the endpoints were defined differently across the trials. Hypothesis The apparent heterogeneity of the meta‐analysis of kidney composite outcomes of SGLT2 inhibitor trials will be substantially reduced by using a consistent assessment of sustained ≥40% decline in eGFR/chronic kidney dialysis/transplantation/renal death across trials. Methods We performed a meta‐analysis of kidney composite outcomes from the four SGLT2 cardiovascular outcome trial programs conducted in general type 2 diabetes mellitus populations, which included, as a surrogate of progression to kidney failure, a sustained ≥40% decline in eGFR along with kidney replacement therapy and kidney death. The trials assessed were VERTIS CV (NCT01986881), CANVAS Program (NCT01032629 and NCT01989754), DECLARE‐TIMI 58 (NCT01730534), and EMPA‐REG OUTCOME (NCT01131676). Results Data from the trials comprised 42 516 individual participants; overall, 998 composite kidney events occurred. SGLT2 inhibition was associated with a significant reduction in the kidney composite endpoint (HR 0.58 [95% CI 0.51–0.65]) and with a highly consistent effect across the trials (Q statistic p = .64; I 2 = 0.0%). Conclusions Our meta‐analysis highlights the value of using similarly defined endpoints across trials and supports the finding of consistent protection against kidney disease progression with SGLT2 inhibitors as a class in patients with type 2 diabetes mellitus who either have established atherosclerotic cardiovascular disease or are at high cardiovascular risk with multiple cardiovascular risk factors.