Post-transplant diabetes mellitus and preexisting liver disease - a bidirectional relationship affecting treatment and management

Table 1 Proven and possible effects of glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors in diabetes and metabolism-associated fatty liver disease before and after liver transplantation

Therapy effect	NAFLD	T2DM	PTDM	Post-LT liver disease
GLP-1RA proven	Improvement in liver enzymes and intrahepatic triglycerides content[113-116,130,131]	Improvement of glycemia; increase insulin secretion in a glucose-dependent manner; inhibit glucagon secretion; weight loosing effect; cardiovascular protection[103-106]	Improvement of insulin and normalization of glucagon concentrations[150]	None metabolized by liver, no dose adjustments needed[156]
			Resistance against toxicity of IS drugs in vitro[154]
				Weight loss during first weeks after LT[158]
	Improvements in weight, body mass index, glycemic control, liver enzymes, hsCRP[117]
			Prevention of steroid diabetes[155]
	Improvement in liver histology[118-120]
	Resolution of NASH[122,127-129]
GLP-1RA possible	Reduction of hepatic steatosis; anti-inflammatory effect[107-112]		Improvement of cardiovascular outcomes[103-106], GI side effects potentiating GI disturbances caused by IS drugs[157]
SGLT-2i proven	Reduction of liver enzymes[65,135-142]	Improvement of glycemia; weight loosing effect; decrease in systolic and diastolic blood pressures; cardiovascular benefit[132-134]	Reduction of weight and blood pressure[162]
			Improved glycemia[163]
	Reduction of body weight and body fat[143-147]
SGLT2i possible	Reduction of oxydative stress and inflammation[143-147]		Genitourinary infections[164]	Reduction in fat mass and visceral adipose tissue[165]

GLP-1RA: Glucagon-like peptide-1 receptor agonists; IS: Immunosuppressive; LT: Liver transplant; NAFLD: Non-alcoholic fatty liver disease; T2DM: Type 2 diabetes mellitus; PTDM: Post-transplant diabetes mellitus; SGLT2i: Sodium-glucose cotransporter 2 inhibitors.