# Pharmacologic Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease in the Context of Type 2 Diabetes

**Authors:** Konstantinos Malandris, Konstantinos Charalampidis, Rohit Loomba, Emmanouil Sinakos

PMC · DOI: 10.1007/s11892-026-01621-w · Current Diabetes Reports · 2026-03-14

## TL;DR

This review discusses how medications for type 2 diabetes can also treat fatty liver disease, highlighting promising drugs like semaglutide and new treatments in development.

## Contribution

The paper provides an updated overview of pharmacologic treatments for MASLD in T2D, emphasizing recent approvals and emerging therapies.

## Key findings

- GLP-1 RAs, SGLT2 inhibitors, and pioglitazone show benefits for steatohepatitis in T2D patients.
- Semaglutide has the strongest evidence for reducing liver fibrosis.
- New therapies like retatrutide and resmetirom are showing promise in treating MASLD.

## Abstract

Metabolic dysfunction–associated steatotic liver disease (MASLD) is highly prevalent among individuals with type 2 diabetes (T2D). This review summarizes current evidence on the pharmacologic treatment of MASLD, with emphasis on agents currently approved for the management of T2D.

Among glucose-lowering therapies, GLP-1 RAs, dual GIP/GLP-1 RAs, pioglitazone, and SGLT2 inhibitors demonstrate meaningful benefits in steatohepatitis. Semaglutide provides the most robust evidence for fibrosis benefit, while data suggest potential antifibrotic effects of tirzepatide and dapagliflozin. Resmetirom and semaglutide are the only agents specifically approved for MASLD. An expanding pipeline of dual glucagon/GLP-1 and triple GIP/GLP-1/glucagon agonists such as retatrutide has shown marked reductions in liver fat and signals of MASH benefit. Additional therapies, including pan-PPAR agonists, and FGF21 analogues are advancing through phase 3 development.

The therapeutic landscape is rapidly evolving toward integrated metabolic, hepatic, and cardiovascular risk reduction in T2D and MASLD.

## Linked entities

- **Chemicals:** semaglutide (PubChem CID 56843331), tirzepatide (PubChem CID 163285897), dapagliflozin (PubChem CID 9887712), resmetirom (PubChem CID 15981237)
- **Diseases:** type 2 diabetes (MONDO:0005148), metabolic dysfunction–associated steatotic liver disease (MONDO:0013209), MASH (MONDO:0007027)

## Full-text entities

- **Genes:** FGF21 (fibroblast growth factor 21) [NCBI Gene 26291], DPP4 (dipeptidyl peptidase 4) [NCBI Gene 1803] {aka ADABP, ADCP2, CD26, DPPIV, TP103}, SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}, GIP (gastric inhibitory polypeptide) [NCBI Gene 2695], INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, GCG (glucagon) [NCBI Gene 2641] {aka GLP-1, GLP1, GLP2, GRPP}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, GLP1R (glucagon like peptide 1 receptor) [NCBI Gene 2740] {aka GLP-1, GLP-1-R, GLP-1R}, DGAT2 (diacylglycerol O-acyltransferase 2) [NCBI Gene 84649] {aka ARAT, GS1999FULL, HMFN1045}, THRB (thyroid hormone receptor beta) [NCBI Gene 7068] {aka C-ERBA-2, C-ERBA-BETA, ERBA2, GRTH, NR1A2, PRTH}
- **Diseases:** insulin resistance (MESH:D007333), Metabolic Dysfunction (MESH:D008659), weight gain (MESH:D015430), hepatocyte injury (MESH:D014947), myocardial infarction (MESH:D009203), CKD (MESH:D012080), stroke (MESH:D020521), prediabetes (MESH:D011236), Weight loss (MESH:D015431), NAFLD (MESH:D065626), T2D (MESH:D003924), obese (MESH:D009765), death (MESH:D003643), F2-F3 fibrosis (MESH:D005355), function (MESH:D003291), renal (MESH:D006030), renal impairment (MESH:D007674), overweight (MESH:D050177), HCC (MESH:D006528), ballooning (MESH:D054549), hyperglycemia (MESH:D006943), heart failure (MESH:D006333), MASLD (MESH:D008107), cirrhotic (MESH:D000094724), cardiovascular (MESH:D002318), hepatic inflammation (MESH:D007249), MASH (MESH:D005234), adiposity (MESH:D018205), hypoglycemia (MESH:D007003), Chronic kidney disease (MESH:D051436), Liver Fibrosis (MESH:D008103), atherosclerotic cardiovascular disease (MESH:D050197), diabetes (MESH:D003920)
- **Chemicals:** DD01 (-), vitamin E (MESH:D014810), Thiazolidinediones (MESH:D045162), vildagliptin (MESH:D000077597), Sulfonylureas (MESH:D013453), aspirin (MESH:D001241), fatty acid (MESH:D005227), Resmetirom (MESH:C588408), exenatide (MESH:D000077270), Mazdutide (MESH:C000719829), Metformin (MESH:D008687), RA (MESH:D011883), degludec (MESH:C571886), Glucose (MESH:D005947), lipid (MESH:D008055), Pioglitazone (MESH:D000077205), dapagliflozin (MESH:C529054), Lanifibranor (MESH:C000619516), sitagliptin (MESH:D000068900), triglyceride (MESH:D014280), empagliflozin (MESH:C570240)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** A3 adenosine, rs738409148

## Full text

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## Figures

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## References

5 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989002/full.md

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Source: https://tomesphere.com/paper/PMC12989002