Physicians' Academy for Cardiovascular Education

SGLT2i improves kidney outcomes regardless of an eGFR dip

News - June 8, 2020

Kidney implications of the initial eGFR response to SGLT2 inhibition with empaglifozin: the 'eGFR dip' in EMPA-REG OUTCOME

Presented at the virtual ERA-EDTA congress by Bettina J Kraus (Würzburg, Germany)

Introduction and methods

The SGLT2 inhibitor empagliflozin reduces kidney risk in patients with T2DM and established CVD. Treatment with empagliflozin induces an initial dip in eGFR. This dip has been observed across the class of SGTL2 inhibitors. Although largely reversible, this initial dip has caused concerns in some clinical settings.

Aims of this post hoc analysis of EMPA-REG OUTCOME were to characterize the initial eGFR dip with empagliflozin use, determine baseline factors that predict an eGFR dip, describe kidney safety and outcomes across predictive factors, and investigate whether the initial eGFR dip affects reduction on kidney outcomes by empagliflozin treatment.

Patients were categorized by % initial eGFR change from baseline to week 4 as eGFR dipper: >10% decline, eGFR intermediate: >0 to ≤10% decline, eGFR non-dipper: no decline.

Main results


This post-hoc analysis of the EMPA-REG OUTCOME showed that approximately 1 in 4 patients on empagliflozin experienced an eGFR dip >10% . Second, diuretic therapy use and higher KDIGO risk were independent predictors for an initial eGFR dip >10% with empagliflozin. Third, empagliflozin was safe across subgroups with higher predictive OR for an eGFR dip. Finally, empagliflozin improved kidney outcomes regardless of an eGFR dip.


In response to a question about the effect of RAASi on dipping, Kraus answered they studied this. First, she said, it is important to note that ~80% of patients in the EMPA-REG OUTCOME trial were using RAAS inhibitors at baseline. Analysis of predictive value of use of ACEi/ARBs showed there was an increased risk of dipping in those on ACEi/ARBs, but there was no interaction with empagliflozin treatment.

There was a question about when to worry with regard to eGFR dip. Kraus said to always take the clinical setting into account and exclude other causes such as AKI. According to her, <20% change in eGFR can be regarded as within the clinical range. In this subanalysis, there were no safety signals with a cut-off of 10%.

‘Is it necessary to adjust the dose of loop diuretics after initiating SGLT2 inhibitors’, someone asked. Kraus replied no difference in volume depletion has been observed between those on empagliflozin vs. placebo, but volume depletion has to be taken into account when adding SGLT2i in a patients on diuretic therapy.

- Our reporting is based on the information provided at the ERA-EDTA congress -

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