Reduced renal events with empagliflozin in Asian patients with T2D
Asian patients with type 2 diabetes (T2D) and existing cardiovascular disease (CVD) who received empagliflozin in the EMPA-REG OUTCOME* trial had a reduced risk of adverse renal events, a finding consistent with that of the overall trial population.
Previous studies have suggested an elevated risk for diabetic kidney disease among Asian patients with T2D, said the researchers. [Diabet Med 2013;30:956-963; Kidney Int 2006;69:2057-2063] “[Results from the present study] suggest the potential for empagliflozin to reduce the burden of early morbidity and mortality from diabetic kidney disease associated with Asian race in patients with T2D,” they said.
Researchers performed a subgroup analysis of the 1,517 Asian patients** (26.1 percent) with T2D and established CVD in the EMPA-REG OUTCOME cohort (n=7,020) who received either empagliflozin 10 mg, 25 mg, or placebo once/daily plus standard of care. Almost 72 percent of the Asian cohort was on angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin-receptor blockers (ARBs). Patients were observed for a median 3.3 years.
The incidence of adverse renal outcomes was numerically higher in the Asian subgroup than in the overall population (15.5 percent vs 12.7 percent for incident or worsening nephropathy and 13.7 percent vs 11.2 percent for progression to macroalbuminuria).
Asian patients who received empagliflozin experienced a reduction in the risk of incident or worsening nephropathy compared with those who received placebo (15.5 percent vs 21.8 percent, hazard ratio [HR], 0.64, 95 percent confidence interval [CI], 0.49–0.83) as well as a reduction in the risk of progression to macroalbuminuria (13.7 percent vs 19.3 percent, HR, 0.64, 95 percent CI, 0.49–0.85). [J Diabetes Investig 2018;doi:10.1111/jdi.12971]
There was also a 52 percent reduction in the risk of the composite of doubling of serum creatinine plus eGFR*** ≤45 mL/min/1.73m2, renal replacement therapy initiation, and renal-related death in empagliflozin compared with placebo recipients (1.8 percent vs 3.6 percent, HR, 0.48, 95 percent CI, 0.25–0.92).
Asian patients on empagliflozin also experienced a rapid reduction in UACR# at week 12 compared with those on placebo which was maintained through week 164, regardless of UACR status at baseline. Empagliflozin recipients also experienced sustained improvement in albuminuria status and a slower eGFR decline, while deterioration in albuminuria status was more common among placebo than empagliflozin recipients, with all these effects in Asian patients consistent with that of the overall trial population.
“[The slower decline in eGFR and reduced risk of albuminuria progression] were seen in addition to renin-angiotensin-aldosterone system inhibition in the majority of patients, suggesting that the mechanism of action of empagliflozin might complement that of ACE inhibitors and ARBs,” said the researchers.
Asian patients with eGFR <60 mL/min/1.73 m2 were more likely to experience serious adverse events (AEs), drug-related AEs, and AE-related discontinuations, as well as acute renal failure, bone fracture, hyperkalaemia, oedema, and volume depletion than those with eGFR ≥60 mL/min/1.73 m2, with comparable incidence in empagliflozin and placebo recipients. Genital infections were more common in empagliflozin than placebo recipients.
The effect of empagliflozin on renal outcomes could be due to multiple mechanisms including improvements in arterial stiffness, serum uric acid levels, and tubulointerstitial hypoxia, but most likely driven by a reduction in intraglomerular pressure, said the researchers.
“In Asian patients with T2D, albuminuria has previously been reported to increase the risk of adverse kidney outcomes, and the magnitude of changes in proteinuria and protection of kidney function observed with empagliflozin in the present study might yield the potential to translate into clinical practice by delaying the need for dialysis by several years,” they said.