Acute eGFR decline with SGLT2 inhibitors does not affect outcome
medwireNews: The benefits of treatment with sodium-glucose cotransporter (SGLT)2 inhibitors are not negated by the initial decline in estimated glomerular filtration rate (eGFR) commonly seen with these drugs, show post-hoc analyses of the EMPA-REG OUTCOME and CREDENCE trials.
The findings from both trials were presented as posters at the virtual 56th EASD Annual Meeting.
In EMPA-REG OUTCOME, 28.3% of patients who were randomly assigned to receive empagliflozin 10 mg or 25 mg and 13.4% of those assigned to placebo experienced an initial “eGFR dip” of more than 10% from baseline to week 4, reported Bettina Kraus from University Hospital Würzburg in Germany.
Just 1.4% and 0.9%, respectively, experienced a dip of more than 30%.
Kraus and colleagues found that, overall, individuals receiving empagliflozin were a significant 2.7 times more likely than those receiving placebo to experiencing an initial fall in eGFR of more than 10%.
However, this likelihood was significantly associated severity of kidney disease (based on KDIGO criteria) and/or diuretic use. Specifically, the odds ratios ranged from 1.6 among people with low KDIGO risk who were not receiving diuretics to 4.7 among those with high KDIGO risk who were receiving diuretics.
The researchers also found that an initial eGFR dip of more than 10% did not affect empagliflozin-induced risk reduction for cardiovascular death, hospitalization for heart failure, or incident of or worsening nephropathy.
Furthermore, serious adverse event (AE) rates were generally similar or lower with empagliflozin versus placebo irrespective of baseline KDIGO risk category or diuretic use.
Similar results were observed in CREDENCE. In this study, significantly more participants randomly assigned to receive canagliflozin 100 mg versus placebo had an eGFR dip of more than 10% between baseline and week 3 (45 vs 21%), said Hiddo Heerspink from the University of New South Wales in Sydney, Australia.
The researchers also found that AE rates were similar across different early eGFR change categories (>10% or >0%–10% decrease vs ≥0% increase), with rates generally lower in the canagliflozin than placebo group.
Heerspink concluded that the data suggest that an acute change in eGFR following canagliflozin initiation “may be no reason for safety concern.”
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