New Advances in Diabetes Drugs Are Transforming Treatment of Liver Disease

A rapidly evolving wave of therapies originally developed for type 2 diabetes (T2D) is reshaping how clinicians approach metabolic dysfunction–associated steatotic liver disease (MASLD). In a new paper published in Current Diabetes Reports, researchers have detailed the evolving landscape for the most prevalent liver disorder across the globe.¹

MASLD is closely linked to metabolic conditions such as obesity and T2D, with roughly two-thirds of individuals with diabetes also affected by MASLD. Its more severe form, metabolic dysfunction–associated steatohepatitis (MASH), can lead to liver fibrosis, cirrhosis, and increased mortality. Fibrosis stage has emerged as the strongest predictor of outcomes, and patients with both MASH and T2D face significantly higher risks of liver-related complications and death.

Researchers are increasingly focusing on pharmacologic strategies that can address both metabolic dysfunction and liver disease simultaneously. Recent findings highlight that several glucose-lowering drugs, particularly newer classes, offer meaningful benefits beyond blood sugar control.

“As more long-term data are emerging and novel therapies are being developed and studied, it should be highlighted that the combination of awareness, early patient identification, lifestyle modifications, and use of different drug therapies confer the highest benefit for patients with MASLD and T2D,” wrote the researchers of the landscape.

Among the most promising treatments are glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have emerged as a cornerstone of diabetes care. These drugs not only improve glycemic control and promote weight loss, but also show strong evidence of resolving liver inflammation associated with MASH. Semaglutide (Ozempic and Wegovy; Novo Nordisk), in particular, has demonstrated the most robust clinical data, with studies showing significant rates of disease resolution and even improvement in liver fibrosis in some patients.

Dual-action therapies are also gaining attention, including tirzepatide (Mounjaro and Zepbound; Eli Lilly), which targets both GIP and GLP-1 receptors. The treatment has shown substantial reductions in liver fat and encouraging rates of MASH resolution in clinical trials. While its antifibrotic effects require further confirmation, early data suggest it may play a key role in future treatment strategies.

Another important class, sodium-glucose co-transporter 2 (SGLT2) inhibitors, has demonstrated consistent improvements in liver fat levels, along with cardiovascular and renal benefits. In one randomized trial, dapagliflozin not only reduced liver fat but also improved both MASH resolution and fibrosis outcomes compared with placebo, highlighting its potential as a multifaceted therapy.

Older medications, such as pioglitazone (Actos; Takeda), continue to play a role as well, noted the researchers. Clinical trials have shown that pioglitazone can improve liver inflammation and promote disease resolution, although its impact on fibrosis is more modest. Concerns about side effects, including weight gain and fluid retention, may limit its use in some patients.

By contrast, commonly used diabetes treatments like metformin and DPP-4 inhibitors have not demonstrated meaningful benefits for liver histology and are not recommended specifically for MASLD management.

In addition to repurposed diabetes drugs, therapies developed specifically for MASLD are beginning to emerge. As of late 2025, semaglutide at higher doses and resmetirom (Rezdiffra; Madrigal), a thyroid hormone receptor beta agonist, have received regulatory approval for the treatment of non-cirrhotic MASH.² Resmetirom, in particular, has shown the ability to improve both liver inflammation and fibrosis while also lowering LDL cholesterol, offering potential cardiometabolic advantages.

Beyond currently approved treatments, a pipeline of investigational therapies is expanding the horizon. Novel agents, including dual and triple incretin receptor agonists, fibroblast growth factor 21 (FGF21) analogues, and pan-PPAR agonists, are demonstrating promising results in mid- and late-stage clinical trials. Some of these therapies have shown marked reductions in liver fat and encouraging signals of fibrosis improvement, raising hopes for more comprehensive disease management in the near future.

References:

1. Malandris K, CharalampidisK, Loomba R, Sinakos E. Pharmacologic treatment of metabolic dysfunction-associated steatotic liver disease in the context of type 2 diabetes. Curr Diab Rep. 2026;26(1):6. doi:10.1007/s11892-026-01621-w

2. Tiwari A, Sharma A, Kumar H, et al. Resmetirom for MASH: a comprehensive review of a novel therapeutic frontier. Biomedicines. 2025;13(9):2079. doi:10.3390/biomedicines13092079