Metabolic dysfunction-associated steatotic liver disease, usually shortened to MASLD, is now the most common chronic liver disease on the planet. It sits at the intersection of two widespread conditions: excess body fat and impaired metabolic function. A 2026 state-of-the-art review published in the Journal of Obesity and Metabolic Syndrome by Chan Wah-Kheong and colleagues sets out to map every major pharmacological strategy researchers are currently studying or have recently brought to approval for this condition.
The review makes one thing clear from the start: lifestyle change remains the foundation of management. Sustained weight loss through healthier eating and movement can meaningfully reduce fat buildup in the liver. The problem, the authors note, is that this is genuinely difficult for most people to achieve and maintain over the long term. That gap between what is clinically ideal and what is practically achievable for patients has driven an enormous wave of drug research over the past decade.
The review covers approved agents, a growing family of drugs called incretin-based therapies, and newer molecules known as fibroblast growth factor-21 analogues. It also discusses how non-invasive tests are being used to decide which patients should receive treatment and to track whether the liver is responding. For anyone trying to understand what scientists are actually testing and measuring in this space, this review offers a useful map.
The condition researchers are trying to address
MASLD describes a spectrum of liver conditions driven by metabolic problems rather than alcohol. At the milder end, fat accumulates in liver cells without much inflammation. At the more serious end sits a form called metabolic dysfunction-associated steatohepatitis, or MASH. In MASH, the liver is not just fatty but also inflamed and actively scarring. Over time, that scarring can progress to cirrhosis, a state in which the liver is so heavily scarred it cannot function properly.
The review notes that MASLD is also a significant driver of hepatocellular carcinoma, a form of liver cancer, and of liver-related death more broadly. This makes early identification and intervention a research priority. The authors highlight that, despite progress in treating early-stage MASH, effective pharmacological options for MASH-related cirrhosis remain an unmet need in the field.
Two conditionally approved agents
The review identifies two pharmacological agents that have received conditional approval specifically for MASH. The first is resmetirom, an oral drug that targets thyroid hormone receptor-beta selectively in the liver. The thyroid hormone receptor-beta is involved in regulating fat metabolism in liver cells, and researchers hypothesized that activating it in a liver-directed, selective way could reduce fat accumulation and inflammation without the side effects of systemic thyroid hormone activity. Published trial data referenced in the review suggest resmetirom met meaningful endpoints for liver histology, meaning biopsied tissue showed measurable improvement.
The second approved agent is a glucagon-like peptide-1 receptor agonist, a peptide-based drug class that mimics a natural gut hormone called GLP-1. GLP-1 is released after eating and plays a role in insulin secretion, appetite signaling, and the rate at which the stomach empties. Researchers found that sustained GLP-1 receptor activation produced reductions in liver fat and, in some trial arms, improvements in liver inflammation scores. The review frames this drug class not just as a liver therapy but as a potential backbone of broader metabolic management, including obesity-related conditions.
Incretin-based therapies as a research focus
Incretins are hormones released by the gut in response to food. They coordinate signals between the gut, pancreas, and brain. The GLP-1 receptor agonists just described are one incretin-based class. But the review gives substantial attention to newer molecules that target multiple incretin pathways at once.
Dual agonists target both GLP-1 receptors and receptors for another gut hormone called glucose-dependent insulinotropic polypeptide, or GIP. Triple agonists extend this further by also activating glucagon receptors. The theory is that hitting several metabolic pathways simultaneously produces larger reductions in body weight and liver fat than single-target agents. Early and phase-2 data referenced in the review point toward greater weight loss with these multi-receptor drugs, and researchers are watching closely to see whether that translates into greater liver histology improvements in larger, longer trials.
The review positions these incretin-based therapies as potentially central to what it calls a complication-centric model of obesity management. Rather than treating obesity as a single problem to be addressed on its own, this model focuses on the downstream conditions obesity causes, including fatty liver disease, and asks whether treating the metabolic root aggressively enough can reverse organ-level damage.
Fibroblast growth factor-21 analogues
A second emerging class highlighted in the review involves analogues of a signaling protein called fibroblast growth factor-21, or FGF-21. FGF-21 is produced naturally in the liver and plays roles in fat oxidation, insulin sensitivity, and energy balance. The native protein has a very short half-life in the body, making it impractical as a drug. Researchers have developed modified analogues with longer activity windows.
Trial data cited in the review suggest FGF-21 analogues can reduce liver fat content as measured by imaging, and some trials have shown reductions in markers of liver scarring. The authors describe this class as part of a broader pipeline that may eventually be used in combination with incretin-based therapies, targeting different biological pathways at the same time to achieve additive effects on the liver.
Non-invasive testing and treatment selection
One practical challenge in MASH research has been the reliance on liver biopsy to measure disease severity and treatment response. Biopsy is invasive, carries small but real risks, and is not practical for repeated monitoring. A meaningful portion of the review is devoted to how non-invasive tests are evolving to fill this gap.
Blood-based biomarker panels and imaging techniques such as elastography, which measures liver stiffness as a proxy for scarring, are increasingly being used in trials to identify patients most likely to benefit from treatment and to detect response without repeated biopsies. The review discusses current guidance on how these tools are being incorporated into trial designs and clinical decision frameworks. Researchers note that better non-invasive tools will be essential for scaling up treatment in the large number of people with MASLD who may not have easy access to biopsy centers.
The broader metabolic picture
The review frames MASLD research within a wider shift in how scientists and clinicians think about obesity. Historically, obesity management focused primarily on weight as a number. The paradigm the review describes is different: it centers on what excess adiposity does to specific organs and metabolic systems, and asks whether targeted pharmacological intervention at those specific complications can change long-term outcomes.
The liver is one of the clearest examples of an organ where metabolic dysfunction causes measurable, progressive, and life-threatening damage. The review suggests that incretin-based therapies, given their ability to address body weight, insulin resistance, and liver inflammation simultaneously, may become the central component of management strategies, with other drug classes added based on individual patient profiles.
The authors emphasize that despite real progress, there is still no approved therapy for the most advanced stage of the disease, MASH-related cirrhosis. This remains an active area of research. For now, the literature suggests that the window of greatest benefit is early, before significant scarring has occurred, making identification and intervention at earlier disease stages a research and public health priority.
