Semaglutide Significantly Improves MASH Resolution, but Fibrosis Benefits Remain Limited: Study
Pakistan: A study published in Medicine has found that semaglutide was associated with more than twice the likelihood of resolving metabolic dysfunction-associated steatohepatitis (MASH) compared with placebo. While semaglutide effectively improved liver inflammation, it did not consistently improve or worsen liver fibrosis, highlighting a gap in reversing established scarring. Researchers emphasized the need for longer-term studies and combination treatment strategies to achieve meaningful fibrosis reversal in patients with MASH.
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), and its progressive inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH), are among the leading causes of chronic liver disease worldwide. Despite the increasing disease burden, effective drug therapies remain limited. To evaluate the therapeutic potential of semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely used for type 2 diabetes and obesity, researchers led by Suleman Khan from the Department of Medicine, Khyber Medical College, Peshawar, Pakistan, conducted a systematic review and meta-analysis of placebo-controlled randomized clinical trials.
The researchers conducted a systematic review and meta-analysis of placebo-controlled randomized trials evaluating subcutaneous semaglutide in adults with MASLD or MASH. The certainty of evidence was assessed using the GRADE framework.
The analysis showed that semaglutide more than doubled the likelihood of MASH resolution without worsening liver fibrosis compared with placebo. It also significantly reduced liver enzyme levels, including aspartate aminotransferase, indicating improved liver inflammation.
Key findings from the study include:
- Semaglutide more than doubled the likelihood of MASH resolution without fibrosis progression compared with placebo.
- Liver enzyme levels, including aspartate aminotransferase, were significantly reduced following treatment.
- Improvement in liver fibrosis stage was not statistically significant, although the overall trend favored semaglutide.
- Patients receiving semaglutide experienced substantial weight loss and significant reductions in glycated hemoglobin (HbA1c).
- Gastrointestinal side effects and treatment discontinuation were more frequent with semaglutide than placebo.
- The rate of serious adverse events was comparable between the semaglutide and placebo groups.
The researchers noted that while semaglutide improved steatohepatitis and metabolic health, its effect on reversing liver fibrosis remains uncertain.
They acknowledged limitations, including the short trial duration (48–72 weeks), which prevented assessment of long-term outcomes such as cirrhosis and liver-related mortality. Differences in semaglutide doses, lifestyle interventions, and study populations may also limit the generalizability of the findings.
They concluded that semaglutide is a promising treatment for MASH, particularly in patients with obesity or type 2 diabetes, but emphasized that lifestyle modification remains essential. They called for longer-term studies and combination therapies to determine whether meaningful fibrosis reversal can be achieved.
Reference:
Shah, A., Misbahuddin, F. N. U., Khan, A., Sawaira, F. N. U., Khan, M., Khan, S., Jamal, A., Khalil, I., Ahmed, S., Qadri, M., Iftikhar, H., Ahmed, A., Zai, I. A., Khalid, A. A., & Mohmand, M. S. (2026). Therapeutic role of semaglutide in metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis of placebo-controlled trials with GRADE evidence assessment. Medicine, 105(30), e49916. https://doi.org/10.1097/MD.0000000000049916
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