Eur J Heart Fail. 2020 Nov 29. doi: 10.1002/ejhf.2066. Online ahead of print.
AIMS: Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve clinical outcome in patients with heart failure (HF), but the mechanisms behind their beneficial effects are not yet fully understood. We examined the effects of empagliflozin on renal sodium and glucose handling in patients with acute HF.
METHODS AND RESULTS: This study was a predefined sub-study of a double-blind, randomized, placebo-controlled, multicenter study (EMPA-RESPONSE-AHF). Patients were allocated within 24 hours of an acute HF admission to either empagliflozin 10 mg/day (n=40) or placebo (n=39) for 30 days. Markers of glucose and sodium handling were measured daily during the first 96 hours and at day 30. Patients were 76 (range 38-89) years old and 33% had diabetes. The use of loop diuretics during the first 96 hours was similar in both groups. Empagliflozin increased fractional glucose excretion with a peak after 24 hours (21.8 vs 0.1%; P<0.001), without affecting plasma glucose concentration, while fractional sodium and chloride excretion and urinary osmolality remained unchanged (P for all >0.3). However, empagliflozin increased plasma osmolality (delta osmolality at 72 hours: 5±8 versus 2±5 mOsm/kg; P=0.049). Finally, there was an early decline in eGFR with empagliflozin versus placebo (-10±12 vs. -2±12 mL/min/1.73m2 P=0.009), which recovered within 30 days CONCLUSION: In patients with acute HF, empagliflozin increased fractional glucose excretion and plasma osmolality, without affecting fractional sodium excretion or urine osmolality and caused a temporary decline in eGFR. This suggests that empagliflozin stimulates osmotic diuresis through increased glycosuria rather than natriuresis in patients with acute HF.