Background Empagliflozin (EMPA) reduces cardiovascular and kidney risk in patients with type
2 diabetes (T2D) and cardiovascular disease (CVD). EMPA induces an initial ‘dip’ in
mean estimated glomerular filtration rate (eGFR).
Methods 6,668 Participants of EMPA-REG OUTCOME treated with EMPA 10mg, 25mg or placebo (PBO)
and eGFR available were categorised by initial percentage eGFR change from baseline
at week 4. Impact of an ‘eGFR dip’ >10% on risk reduction with EMPA for CV and kidney
outcomes was assessed in a Cox regression landmark analysis adjusting for such ‘eGFR
dip’.
Results ‘eGFR dip’ of >10% from baseline at Week 4 occurred in 28.3% participants on EMPA
versus 13.4% on PBO; an eGFR decline of >30% in 1.4% and 0.9%, respectively. Odds
ratio [OR; 95% CI] for an ‘eGFR dip’ with EMPA vs. PBO was 2.7 [2.3–3.0]. Diuretic
use and/or higher KDIGO risk category at baseline were predictive of an ‘eGFR dip’
in EMPA vs. PBO. ‘eGFR dip’ did not affect risk reduction for CV death, hospitalization
for heart failure (HHF) or the primary kidney outcome. Adverse events, especially
acute renal failure rates, were lower or similar in EMPA vs. PBO, regardless of baseline
predictive factors for an ‘eGFR dip’.
Conclusion T2D patients with more advanced kidney disease and/or on diuretic therapy at baseline
were more likely to have an initial ‘eGFR dip’ >10% with EMPA. EMPA treatment was
safe and associated with improved CV death, HHF and kidney outcomes, regardless of
baseline predictive factors or such initial ‘eGFR dip’.
