Acute eGFR dip following empagliflozin initiation is not associated with acute kidney injury

According to a large meta-analysis, empagliflozin versus placebo improves measures of acute kidney injury, which in turn are not associated with acute eGFR dip following treatment initiation in patients with type 2 diabetes, heart failure, and chronic kidney disease.

The analysis presented by Dr Natalie Staplin (University of Oxford, UK) used participant-level data from 4 large trials of empagliflozin (across patients with type 2 diabetes, heart failure, and chronic kidney disease), totalling 23,340 participants who had systematic eGFR measurement [1]. The researchers constructed predictive models for acute eGFR dip and conducted a meta-analysis to determine the risk of a ≥50% increase in serum creatinine at 2 consecutive visits and the risk of acute kidney injury, reported as an adverse event.

In the final model, the independent predictors of larger acute eGFR dip were older age, higher eGFR, higher level of albuminuria, use of diuretics, use of renin-angiotensin system inhibitors, higher systolic blood pressure, lower haematocrit, and higher BMI. Additionally, the model predicted a slight increase in drug discontinuation with increasing eGFR dip. Finally, the meta-analysis of adverse event risk showed that empagliflozin versus placebo reduced the risk of a ≥50% increase in serum creatinine (HR 0.80; 95% CI 0.72–0.88; see Figure) and acute kidney injury (HR 0.73; 95% CI 0.63–0.85). Acute eGFR dip was not significantly associated with these outcomes.

Figure: Forest plot of increase in serum creatinine ratio among subgroups [1]



Het, heterogeneity; uACR, urine albumin-creatinine ratio.

“We found that participants with larger acute eGFR dips were only slightly more likely to discontinue empagliflozin or placebo,” concluded Dr Staplin. “Empagliflozin reduced the risk of a ≥50% increase in serum creatinine by 20% and also reduced the risk of acute injury adverse events by 27%. The labels of SGLT2 inhibitors currently include an acute eGFR dip and an acute kidney injury event as adverse events, so the inclusion of these results in the safety labels could be useful information for prescribers.”

1. Staplin N, et al. Impact of acute eGFR dips and markers of disease severity on effects of empagliflozin on acute kidney outcome. 62nd ERA Congress, 4–7 June 2025, Vienna, Austria.

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Posted on 22 August 202525 August 2025