UK: Findings from the RECEDE-CHF Trial

The use of SGLT2 inhibitor empagliflozin in combination with loop diuretics in patients with type 2 diabetes (T2D) and heart failure helps in significant increase in urine volume, show findings from the RECEDE-CHF trial. Also, it caused a significant weight loss, significant increase in electrolyte-free water clearance, and reduced requirement for loop diuretic.

SGLT2 (sodium-glucose cotransporter-2) inhibitors are known to improve heart failure associated outcomes in T2D patients. Given the recent FDA approval for dapagliflozin use in HF patients with reduced ejection fraction, improvement in HF-associated outcomes seen with SGLT2 inhibitors, the coprescription of SGLT2 inhibitors and loop diuretic will become common. Considering this, there arises a need for future mechanistic studies to understand their combined effects.

The aim of the study, published in the journal Circulation, conducted by Chim C. Lang, University of Dundee, Scotland, United Kingdom, and colleagues, is to explore the effects of the SGLT2 inhibitor empagliflozin on diuresis and natriuresis and on the interaction between loop diuretics and SGLT2 inhibitors.

The RECEDE-CHF trial (SGLT2 Inhibition in Combination With Diuretics in Heart Failure) is a randomized, double-blind, placebo-controlled, crossover trial. It included 23 participants with type 2 diabetes and heart failure with reduced ejection fraction who were regular loop diuretic users. The patients 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 to week 6.

Empagliflozin caused a significant increase in urine volume at both day 3 and week 6 compared with placebo, as well as a significant increase in electrolyte-free water clearance.

Key Findings of the Study

• Compared with placebo, empagliflozin caused a significant increase in 24-hour urinary volume at both day 3 (mean difference, 535 mL) and week 6 (mean difference, 545 mL) 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).
• Empagliflozin caused a nonsignificant increase in fractional excretion of sodium at day 3, which was absent at week 6 (mean difference day 3, 0.30%; week 6, 0.11%), and a significant increase in electrolyte-free water clearance at week 6 (mean difference, 312 mL) compared with placebo.
• Empagliflozin also caused significant reductions in body weight and serum urate at week 6.

"These results suggest empagliflozin may have an advantageous diuretic profile in patients with type 2 diabetes and heart failure in addition to loop diuretics, with only a short, transient natriuresis," concluded the authors.

"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," is published in the journal Circulation.

DOI: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.120.048739