Table 4.

Anti-hyperglycemic drugs and considerations in patients with liver cirrhosis^{56,61,72,80-86}

Agent	Main site of elimination	Benefits	Major concerns	Compensated cirrhosis, Child-Pugh A	Decompensated cirrhosis, Child-Pugh B	Decompensated cirrhosis, Child-Pugh C
Metformin	Kidney (dose according to renal function)	Possibly reduce HCC risk	Metabolic acidosis	Safe	Contraindicated	Contraindicated
Sulphonylureas (only second and third generations)	Kidney/protein-bound	-	Hypoglycemia	Safe	Contraindicated	Contraindicated
Glinides*	Liver	-	Hypoglycemia	Caution	Caution	Contraindicated
DPP-4 inhibitors†	Kidney	No hypoglycemia risk	Lack of efficacy	Safe	Safe	Contraindicated
SGLT2-inhibitors	Liver (small amount by the kidney)	No hypoglycemia risk, benefit in MASLD	Dehydration, hypotension	Safe	Safe	Contraindicated
GLP1 RAs (human GLP1-based), e.g., liraglutide, dulaglutide, and semaglutide	Degraded by DPP-4 enzyme	No hypoglycemia risk, benefit in MASLD	Excessive weight loss/malnutrition	Safe	Safe	Contraindicated
GLP1 RAs (exendin based), e.g., lixisenatide and exenatide	Kidney	No hypoglycemia risk	Excessive weight loss/malnutrition	Safe	Contraindicated	Contraindicated
Acarbose	Gastrointestinal tract	No hypoglycemia risk	Lack of efficacy	Safe	Safe	Contraindicated
Pioglitazone	Liver	Benefits NASH without cirrhosis	Fluid retention	Caution	Contraindicated	Contraindicated
Insulin (insulin analogues preferred)	Liver	Safe in all degrees of liver cirrhosis	Hypoglycemia	Safe	Safe	Safe

*Repaglinide and ^†Vildagliptin are contraindicated in cirrhosis.

HCC, hepatocellular carcinoma; DPP-4, dipeptidyl peptidase-4; SGLT2, sodium glucose co-transporter-2; MASLD, metabolic dysfunction-associated steatotic liver disease; GLP1 RA, glucagon-like peptide-1 receptor agonist; NASH, non-alcoholic steatohepatitis.