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Effects of empagliflozin on conventional and exploratory acute and chronic kidney outcomes: an individual participant-level meta-analysis

Herrington WG, Che ZJ, Sardell R, Roddick AJ, Judge PK, Wanner C, Hauske SJ, Anker S et al.

The lancet. Diabetes & endocrinology, 2025

23 participants · 10 citations

Abstract

BACKGROUND

Uncertainty remains about effects of sodium-glucose co-transporter-2 (SGLT2) inhibition on kidney outcomes in individuals with slowly progressive chronic kidney disease (eg, low albuminuria) and those at risk of large acute estimated glomerular filtration rate (eGFR) dips on initiation of such treatment. We aimed to explore the effects of empagliflozin on a range of kidney outcomes in these population subtypes.

METHODS

In this meta-analysis, we used individual-level data from 23 340 participants in four large placebo-controlled trials (EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, and EMPA-KIDNEY) to assess the effects of empagliflozin on conventional and exploratory acute and chronic kidney outcomes. We then assessed whether effects varied by predicted size of the acute eGFR dip on treatment initiation or among other key population subtypes using tests for heterogeneity and trend. The individual-level data were requested from Boehringer Ingelheim (Ingelheim, Germany).

FINDINGS

Compared with placebo, allocation to empagliflozin reduced the risk of a marker of acute kidney injury (a ≥50% increase in serum creatinine in consecutive follow-up samples) by 20% (hazard ratio 0·80 [95% CI 0·72-0·88]; 1573 outcomes), acute kidney injury adverse events by 27% (0·73 [0·63-0·85]; 694 outcomes), a categorical chronic kidney disease progression outcome by 30% (0·70 [0·63-0·78]; 1403 outcomes), and kidney failure by 34% (0·66 [0·55-0·79]; 490 outcomes). Empagliflozin…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 23 participants or records.

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