When two expensive medications both improve liver scarring, which one should doctors prescribe? A new analysis presented at Digestive Disease Week 2026 found that semaglutide emerged as the more cost-effective choice for treating metabolic dysfunction-associated steatohepatitis (MASH), a serious form of fatty liver disease, compared to resmetirom. The finding matters because MASH now affects an estimated 350 million people worldwide and is becoming the leading cause of cirrhosis and liver cancer.

Why Does Cost-Effectiveness Matter for Liver Disease Treatment?

Both semaglutide and resmetirom showed similar improvements in liver scarring in clinical trials, with about 26% of patients in each group experiencing fibrosis improvement. However, the economic analysis revealed significant differences in overall value. Researchers from Yale New Haven Health compared data from the ESSENCE trial for semaglutide with the MAESTRO-NASH trial for resmetirom, modeling how each drug would affect patients over time as their liver disease progressed.

The cost difference was striking. At 10 years, the incremental cost-effectiveness ratio for semaglutide was approximately $44,000 compared to more than $100,000 for resmetirom. This means semaglutide delivered more health benefit per dollar spent. The analysis also measured quality-adjusted life years (QALYs), a standard metric that combines how long patients live with how well they live, and semaglutide performed better on this measure as well.

"These are different ways of answering one simple question: Are we getting enough clinical benefit for our cost?" explained Sarpong Boateng, MD, MPH, a resident at Yale New Haven Health/Bridgeport Hospital, who presented the findings.

Sarpong Boateng, MD, MPH, Resident at Yale New Haven Health/Bridgeport Hospital

The stakes are high. MASH with moderate-to-advanced scarring is expected to increase from 6.7 million cases in 2020 to 11.7 million by 2050 in the United States alone. The disease now costs the healthcare system an estimated $76 billion annually in direct costs, making treatment decisions not just clinical but also economic and population-level decisions.

What Sets Semaglutide Apart Beyond Liver Health?

While both medications reduced the risk of cirrhosis, liver cancer, and death in the analysis, semaglutide offered an additional advantage: cardiovascular benefits. Semaglutide has been shown in large clinical trials to reduce heart disease and stroke risk, benefits that resmetirom has not yet been studied for. This extra benefit strengthened semaglutide's value proposition, though researchers acknowledged that future studies should evaluate whether resmetirom also provides cardiovascular protection.

"Semaglutide offered the best balance of cost, liver outcomes, and cardiovascular benefits. This shows that efficacy alone is not enough, but value also matters," Boateng stated.

Sarpong Boateng, MD, MPH, Resident at Yale New Haven Health/Bridgeport Hospital

Even when researchers removed the cardiovascular benefits from their analysis, semaglutide still outperformed resmetirom on cost-effectiveness measures. This suggests that the liver-specific benefits and lower cost of semaglutide make it the stronger choice regardless of heart health considerations.

How to Understand Treatment Value in Liver Disease

• Fibrosis Improvement: Both medications achieved similar rates of liver scarring reversal at around 26%, meaning the liver-specific benefits were comparable between the two drugs.
• Long-Term Cost Savings: Semaglutide's lower price and better health outcomes combined to create a cost-effectiveness ratio roughly half that of resmetirom over a 10-year period.
• Additional Health Benefits: Semaglutide's proven cardiovascular benefits add extra value beyond liver protection, reducing heart disease and stroke risk in patients with fatty liver disease.
• Real-World Applicability: The analysis used data from large, well-designed clinical trials with patient populations similar to those seen in clinical practice, with average body mass index (BMI) around 35 and about 60% having diabetes.

What About GLP-1 Drugs Versus Other Liver Treatments?

A second study presented at the same conference compared GLP-1 receptor agonists (the drug class that includes semaglutide) with SGLT2 inhibitors, another class of medications used for metabolic liver disease. Researchers analyzed data from 90,030 patients in each treatment group and found that GLP-1 drugs were associated with significantly lower all-cause mortality at one year (1.36% versus 2.13%) and at three years (4.11% versus 4.76%).

GLP-1 drugs also reduced the risk of ascites, a dangerous fluid buildup in the abdomen that signals advanced liver disease, at both one year and three years. Emergency hospitalizations were also lower in the GLP-1 group. However, both drug classes showed similar rates of cirrhosis and liver cancer development, suggesting they work through different mechanisms.

"GLP-1s help promote weight loss, improve insulin resistance, and reduce hepatic and adipose inflammation. These effects may reduce the physiologic stress that triggers ascites and acute hospitalization," explained Asifa Manzoor, MBBS, internal medicine resident at Aiken Regional Medical Centers.

Asifa Manzoor, MBBS, Internal Medicine Resident at Aiken Regional Medical Centers

Researchers emphasized that SGLT2 inhibitors remain valuable medications with proven benefits for cardiometabolic health and liver scarring reduction. The comparison was not meant to suggest one class is superior overall, but rather to help clinicians understand the specific advantages of each approach.

What Do These Findings Mean for Patients?

For patients diagnosed with MASH and moderate-to-advanced liver scarring, these findings suggest that semaglutide may be a more cost-effective first-line treatment option. The analysis supports using semaglutide as an initial therapy for patients with F2 or F3 fibrosis (moderate-to-advanced scarring) who do not yet have cirrhosis. However, individual treatment decisions should still be made in consultation with a hepatologist or gastroenterologist, as factors like medication tolerance, other health conditions, and insurance coverage may influence the choice.

The research highlights an important shift in how liver disease is being treated. Rather than waiting for liver damage to become severe, medications that improve both liver health and overall cardiovascular health are now available to slow or reverse the disease in its earlier stages. As MASH continues to rise globally, understanding which treatments offer the best value will help healthcare systems allocate resources effectively while improving patient outcomes.