Role of sodium-glucose cotransporter 2 inhibitors in liver diseases

Table 4 List of adverse events with sodium-glucose cotransporter 2 inhibitors

Adverse events	Description	Incidence
Genital mycotic infections	Common due to increased glucose in the urine, fostering fungal growth, more frequent in premenopausal females. UTIs are also common, especially in older individuals or those with recurrent infections	Up to 15% for genital mycotic infections; UTIs are common, but the exact incidence varies
DKA	It is rare but serious; it can occur with a modest glucose increase, with a higher risk in patients with cirrhosis during fasting, dehydration, or illness. Canagliflozin and dapagliflozin pose a greater risk of euglycemic DKA than empagliflozin	Rare but reported cases in patients with cirrhosis
Acute kidney injury	Higher risk when combined with diuretics, especially in those with renal impairment (GFR < 60 mL/min/1.73 m2). Patients with sepsis or dehydration need close monitoring	There has not been a significant increase in trials, but caution is to be exercised in high-risk populations
Fractures and amputations	Canagliflozin is linked to increased fracture risk and nearly doubled lower limb amputation risk, particularly in patients with peripheral vascular disease	CANVAS trial: Higher fracture risk (15.4 fractures per 1000 person-years); amputation risk nearly doubled. Incidence of fractures in other trials- not significantly higher
Fournier’s gangrene	Rare but life-threatening necrotizing genital and perineal infection. Food and Drug Administration has issued warnings and requires immediate medical attention if symptoms arise	Extremely rare but serious; the exact incidence is unknown
Hypotension and dehydration	Due to the mild diuretic effect, it causes a 3-5 mmHg drop in BP. Risk increases in patients on antihypertensives or those prone to dehydration. Patients with cirrhosis and splanchnic vasodilation require monitoring	1.2% to 1.5%, especially in patients prone to dehydration or on antihypertensives
Other side effects	Includes mild hypoglycemia (especially with sulfonylureas or insulin), fatigue, arthralgia, and mild allergic reactions (rash, urticaria). Generally mild and reversible	Variable, mild in most cases
Concerns in chronic liver disease	Generally, it is well tolerated in mild-to-moderate liver impairment, but isolated reports of drug-induced liver injury exist. Patients with advanced cirrhosis (Child-Pugh C) require caution [increased risk of infections, particularly UTIs and sepsis, in decompensated cirrhosis]	Study on empagliflozin: 10 patients with cirrhosis, 8 had an adverse event, 3 reported a serious adverse event (1 could be attributed to empagliflozin). The overall frequency of adverse events is similar to earlier phase 3 trials of SGLT2 inhibitors

BP: Blood pressure; DKA: Diabetic ketoacidosis; GFR: Glomerular filtration rate; SGLT2: Sodium-glucose cotransporter 2; UTI: Urinary tract infections.