Redefining weight management after liver transplantation with glucagon-like peptide one and gastric inhibitory polypeptide receptor agonists

Table 1 Key drivers of metabolic disorders after liver transplantation: A mechanistic basis for glucagon-like peptide-1 therapy

Pathophysiology	Triger	Resultant metabolic disorder	Role of GLP-1, dual GLP-1/glucose-dependent insulinotropic polypeptide
β-cell toxicity, reduced insulin secretion, and peripheral insulin resistance[24,25]	Immunosuppressant agents	Post-transplant diabetes mellitus[24,25]	Promotes and increases insulin secretion, reduces glucagon secretion, Improves β-cell function, and Improved insulin sensitivity[24,26,27]
Altered lipid metabolism (increased very LDL production, decreased lipoprotein lipase activity and impaired lipid clearance)[28]	Immunosuppressant agents. Post-transplant metabolic changes	Dyslipidaemia[29]	Reduces triglycerides, LDL cholesterol and very LDL production[30,31]
Return of appetite, resolution of catabolic cirrhosis state and visceral fat accumulation[32]	Postoperative lifestyle	Weight gain (obesity) and adipose dysfunction[33]	Act on hypothalamic satiety centres, slow gastric emptying, reduce caloric intake, reduces liver fat contents, improve hepatic lipid metabolism[34,35]
Insulin resistance, increased free fatty acid flux, de novo lipogenesis	Pre-existing metabolic disease	Pre-existing metabolic risk factors (obesity, diabetes, fatty liver or metabolic-associated steatotic liver disease)[36,37]	Decrease hepatic de-novo lipogenesis, reduce liver fat contents, increase fatty-acid oxidation and reduce free-fatty-acid release from adipose tissue[30,38,39]
Combination of insulin resistance, visceral adiposity, dyslipidaemia	Immunosuppressant agents[32,40]	Metabolic syndrome	In addition to the above mechanisms, they reduce systemic inflammation, improve adipokine profiles and decrease oxidative stress[31,32,41,42]
Loss of renal magnesium which aggravates insulin resistance	Immunosuppressant agents[43,44]	Renal/electrolyte disturbances[43,44]	Modulation of tubular sodium handling and improved metabolic regulation[45]

GLP-1: Glucagon-like peptide-1; LDL: Low-density lipoproteins.