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Empagliflozin plus loop diuretics significantly increase urine volume in diabetes with HF
UK: 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 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. 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 include:
- 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
MSc. Biotechnology
Medha Baranwal joined Medical Dialogues as an Editor in 2018 for Speciality Medical Dialogues. She covers several medical specialties including Cardiac Sciences, Dentistry, Diabetes and Endo, Diagnostics, ENT, Gastroenterology, Neurosciences, and Radiology. She has completed her Bachelors in Biomedical Sciences from DU and then pursued Masters in Biotechnology from Amity University. She has a working experience of 5 years in the field of medical research writing, scientific writing, content writing, and content management. She can be contacted at  editorial@medicaldialogues.in. Contact no. 011-43720751
Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751