Role of sodium-glucose cotransporter 2 inhibitors in liver diseases

Table 2 Studies on the role of sodium-glucose cotransporter 2 inhibitors in patients with cirrhosis

Ref.	Country, study design	No. of patients	Male sex/age, in years/etiology/DM	Drug	Indication	Outcome
Montalvo-Gordon et al[52], 2020	Mexico, case series	3	33.3%/53-63/NAFLD: 100%/100%	Empaglifozin: 1, canagliflozin: 2	Diuretic intractable ascites	At 12-24 months of follow-up, all 3 patients had resolution of ascites (off-diuretics)
Kalambokis et al[53], 2021	Greece, case report	1	Male/54/PBC/yes	Empaglifozin	Refractory ascites and hepatic hydrothorax	Increased natriuresis with resolution of ascites, hydrothorax within 4 months (off diuretics), and improvement in glycemic control and liver function
Saffo et al[59], 2021	United States, retrospective	78	65%/61 (22-88)/NAFLD: 50%, Alcohol: 19%/NA	Empagliflozin: 33; Canagliflozin: 17; Dapagliflozin: 13; Ertugliflozin: 1; Multiple: 14	NA	7 patients had AEs, including 6 with mycotic genital infections. There were no episodes of AKI, hypotension, significant electrolyte disturbances, or hepatotoxicity
Saffo et al[60], 2021	United States, retrospective	502	99%/67 ± 7/NAFLD: 47%/100%	NA	Prevention of ascites and death in patients with compensated cirrhosis and DM on metformin	Compared to DPP-4 inhibitors, SGLT2 inhibitors had a reduced risk of mortality (aHR: 0.33, 0.11-0.99) but not ascites
Huynh et al[61], 2023	United States, retrospective	1411	48.6%/60.3 ± 11.7/NA/100%	Empagliflozin: 863; Dapagliflozin: 395; Canagliflozin: 175; Ertugliflozin: 12	Prevention of morbidity and mortality in patients with compensated cirrhosis and DM on metformin	Combination of SGLT2 inhibitors with metformin reduced the risk of mortality (HR = 0.57, 0.41-0.81), decompensation (HR = 0.63, 0.43-0.93), and HCC (HR = 0.43, 0.21-0.88) compared with those on metformin monotherapy
Bakosh et al[56], 2024	Egypt, RCT	21	42.9%/65.7 ± 5/MASLD: 52.4%, HCV: 47.6%/42.9%	Empaglifozin	Refractory ascites	The need for LVP (42.9% vs 100%) and the proportion of patients with ascites (76.2% vs 100%) were significantly lower with SGLT2 inhibitors
Shen et al[55], 2024	Australia, prospective	10	60%/58.5 ± 10.1/alcohol: 60%, HCV: 30%/NA	Empaglifozin	NA	8 (80%) reported AEs, and 3 (30%) reported serious AEs with the frequency being similar in those without cirrhosis
Singh et al[54], 2024	India, RCT	20	90%/52.1 ± 8.6/alcohol: 50%, MASLD: 25%/NA	Dapagliflozin	Recurrent ascites	Complete (15% vs 0%) and partial control (55% vs 35%) of ascites at 6 months was significantly better with SGLT2 inhibitors
Yoshimura et al[57], 2024	Japan, case report	1	Male/45/alcohol/no	Dapagliflozin	IgA nephropathy	Significant reduction in proteinuria within 1 week of treatment

AE: Adverse events; aHR: Adjusted hazard ratio; AKI: Acute kidney injury; DM: Diabetes mellitus; DPP-4: Dipeptidyl peptidase 4; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; HR: Hazard ratio; IgA: Immunoglobulin A; LVP: Large-volume paracentesis; MASLD: Metabolic dysfunction-associated steatotic liver disease; NA: Not available; NAFLD: Nonalcoholic fatty liver disease; PBC: Primary biliary cirrhosis; RCT: Randomized controlled trial; SGLT2: Sodium-glucose cotransporter 2.