Effects of sodium glucose co-transporter-2 inhibitors and glucagon like peptide-1 receptor agonists in diabetic metabolic dysfunction-associated steatotic liver disease management

Table 1 Summary of the effects of sodium-glucose co-transporter 2 inhibitor in metabolic dysfunction-associated steatotic liver disease

Key components	Details/evidence	Clinical implication
Metabolic effects	Decreased renal glucose reabsorption → glycosuria → improved glycemic control and caloric loss	Weight reduction and improved insulin resistance
Hepatic lipid metabolism	Increased β-oxidation, decreased novo lipogenesis (via AMPK activation, reduced SREBP-1c signaling)	Reduction in hepatic steatosis
Insulin sensitivity	Improved peripheral and hepatic insulin sensitivity	Reduced lipotoxicity and hepatic fat accumulation
Anti-inflammatory effects	Decreased pro-inflammatory cytokines, decreased oxidative stress	Attenuation of steatohepatitis progression
Antifibrotic pathways	Modulation of TGF-β, stellate cell activation, collagen deposition	Potential slowing of fibrosis progression
Autophagy and mitochondrial function	Activation of autophagy and improved mitochondrial efficiency (PubMed)	Reduced hepatocellular injury
Gut-liver axis	Modulation of gut microbiota composition	Emerging contributor to metabolic and inflammatory regulation
Systemic cardiometabolic effects	Weight loss, decreased visceral adiposity, CV and renal protection	Indirect benefit on MASLD progression

SREBP-1c: Sterol regulatory element-binding protein 1c; AMPK: AMP-activated protein kinase; TGF-β: Transforming growth factor-β; CV: Cardiovascular; MASLD: Metabolic dysfunction-associated steatotic liver disease.

Table 2 Metabolic dysfunction-associated steatotic liver disease treatment with sodium-glucose co-transporter 2 inhibitor

Therapeutic strategies	Approach	Details	Clinical positioning
Monotherapy	SGLT2i alone	Effective for metabolic improvement and steatosis reduction	Best suited for MASLD with T2DM
Combination therapy	With GLP-1RA, pioglitazone	Potential synergistic metabolic and hepatic effects (PubMed)	Emerging strategy (not yet standardized)
Patient selection	T2DM + MASLD	Strongest evidence in diabetic populations	First-line metabolic-targeted option
	Non-diabetic MASLD	Less consistent benefit	Consider in selected metabolic phenotype
Treatment duration	Short-term (≤ 24 weeks)	Demonstrates measurable improvement in steatosis	Most RCTs short-term
	Long-term therapy	Needed for fibrosis/hard outcomes	Evidence still limited
Endpoints for monitoring	Imaging (CAP, MRI-PDFF), LSM	Non-invasive monitoring preferred	Surrogate markers widely used
Position in guidelines (emerging)	Adjunct therapy	Not yet MASLD-specific approved therapy	Used based on metabolic indication (T2DM, obesity)

SGLT2i: Sodium-glucose co-transporter 2 inhibitors; GLP-1RA: Glucagon-like peptide-1 receptor agonists; T2DM: Type 2 diabetes mellitus; MASLD: Metabolic dysfunction-associated steatotic liver disease; CAP: Controlled attenuation parameter; MRI-PDFF: Magnetic resonance imaging-proton density fat fraction; LSM: Liver stiffness measurement; RCTs: Randomized controlled trials.