Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination with Loop Diuretics in Patients with Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial

Link to article at PubMed

Circulation. 2020 Aug 29. doi: 10.1161/CIRCULATIONAHA.120.048739. Online ahead of print.


Background: Sodium-Glucose Co-Transporter-2 (SGLT2) inhibitors improve heart failure (HF) associated-outcomes in patients with type 2 diabetes (T2D). In patients with HF, SGLT2 inhibitors will likely be co-prescribed with a loop diuretic, but this combined effect is not well-defined. Our aim was to assess the diuretic and natriuretic effect of empagliflozin in combination with loop diuretics. Methods: The RECEDE-CHF trial (NCT03226457) was a randomized, double-blind, placebo-controlled, cross-over trial of patients with T2D and HF with reduced ejection fraction taking regular loop diuretic who were randomized to empagliflozin 25 mg once daily or placebo for 6 weeks with a 2-week washout period. The primary outcome was change in 24-hour urinary volume from baseline at week 6. Results: Twenty-three participants (mean age 69.8 years, 73.9% male, mean furosemide dose of 49.6±31.3mg/day, mean HbA1c 7.9±3.8%) were recruited. Compared to placebo, empagliflozin caused a significant increase in 24-hour urinary volume at both day 3 (mean difference 535 ml, 95% CI 133 to 936, p =0.005) and week 6, (mean difference 545 ml, 95% CI 136 to 954 p = 0.005) after adjustment for treatment order, baseline 24-hour urine volume and percentage change in loop diuretic dose. At 6 weeks empagliflozin did not cause a significant change in 24-hour urinary sodium (mean difference -7.85 mmol/L, 95% CI -2.43 to 6.73, p = 0.57). Empagliflozin caused a non-significant increase in fractional excretion of sodium at day 3 which was absent at week 6 (mean difference day 3: 0.30%, 95% CI -0.03 to 0.63, p=0.09; week 6 0.11%, 95% CI -0.22 to 0.44, p > 0.99) and a significant increase in electrolyte-free water clearance at week 6 (mean difference 312 ml, 95% CI 26 to 598, p=0.026) compared to placebo. Empagliflozin also caused significant reductions in body weight and serum urate at week 6. Conclusions: Empagliflozin caused a significant increase in 24-hour urine volume without an increase in urinary sodium when used in combination with loop diuretic. Clinical Trial Registration: URL: Unique Identifier: NCT03226457.

PMID:32865004 | DOI:10.1161/CIRCULATIONAHA.120.048739

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