TY - JOUR
T1 - A potential novel treatment for cirrhosis-related ascites
T2 - Empagliflozin is safe and tolerable in advanced chronic liver disease
AU - Shen, Ivan
AU - Stojanova, Jana
AU - Yeo, Malcolm
AU - Olsen, Nick
AU - Lockart, Ian
AU - Wang, Max
AU - Roggeveld, Jan
AU - Heerspink, Hiddo J.L.
AU - Greenfield, Jerry R.
AU - Day, Richard
AU - Danta, Mark
N1 - Publisher Copyright:
© 2024 The Author(s). British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
PY - 2024/10
Y1 - 2024/10
N2 - Aims: Advanced chronic liver disease and advanced chronic liver disease-related ascites have a high mortality. The pharmacological treatment of ascites and fluid overload has changed little over time. Empagliflozin, a sodium-glucose cotransporter type 2 inhibitor is an untested potential novel treatment in cirrhosis, as it has survival benefits in heart failure, which has similar pathophysiological fluid overload mechanisms. Before investigating empagliflozin's potential benefit in cirrhosis, its safety must be addressed. Methods: Ten participants (five each with compensated or decompensated advanced chronic liver disease, based on Child–Pugh class) received empagliflozin 10 mg orally daily for 4 weeks with 2 weeks follow-up. Empagliflozin safety, pharmacokinetics and pharmacodynamics were investigated. Results: In total, eight patients (80%) reported an adverse event, and three patients (30%) experienced a serious adverse event, one of which was attributed to empagliflozin. Overall, the frequency of adverse events was similar to previous phase 3 trials of gliflozins. Higher plasma empagliflozin concentrations did not significantly increase the risk of adverse events. Conclusions: Four-week treatment with empagliflozin was safe and well tolerated in patients with advanced chronic liver disease. These preliminary data support assessment of long-term treatment on disease-related and mortality outcomes in patients with cirrhosis through randomized control trials.
AB - Aims: Advanced chronic liver disease and advanced chronic liver disease-related ascites have a high mortality. The pharmacological treatment of ascites and fluid overload has changed little over time. Empagliflozin, a sodium-glucose cotransporter type 2 inhibitor is an untested potential novel treatment in cirrhosis, as it has survival benefits in heart failure, which has similar pathophysiological fluid overload mechanisms. Before investigating empagliflozin's potential benefit in cirrhosis, its safety must be addressed. Methods: Ten participants (five each with compensated or decompensated advanced chronic liver disease, based on Child–Pugh class) received empagliflozin 10 mg orally daily for 4 weeks with 2 weeks follow-up. Empagliflozin safety, pharmacokinetics and pharmacodynamics were investigated. Results: In total, eight patients (80%) reported an adverse event, and three patients (30%) experienced a serious adverse event, one of which was attributed to empagliflozin. Overall, the frequency of adverse events was similar to previous phase 3 trials of gliflozins. Higher plasma empagliflozin concentrations did not significantly increase the risk of adverse events. Conclusions: Four-week treatment with empagliflozin was safe and well tolerated in patients with advanced chronic liver disease. These preliminary data support assessment of long-term treatment on disease-related and mortality outcomes in patients with cirrhosis through randomized control trials.
KW - advanced chronic liver disease
KW - cirrhosis
KW - empagliflozin
KW - population model
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85196190181&partnerID=8YFLogxK
U2 - 10.1111/bcp.16139
DO - 10.1111/bcp.16139
M3 - Article
C2 - 38881155
AN - SCOPUS:85196190181
SN - 0306-5251
VL - 90
SP - 2529
EP - 2538
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 10
ER -