New results from the ESSENCE trial indicate that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), produces a meaningful improvement in liver histology. It provides significant benefits to patients affected by metabolic-associated steatotic liver disease (MASH). The trial, which was conducted in phase 3, included two parts. It enrolled 1,197 participants from 253 clinical sites in 37 countries and looked at the drug’s impact on liver fibrosis and steatohepatitis.
Semaglutide was given as a subcutaneous injection with a once weekly dose of 2.4mg. The primary aim of the trial was to determine a reduction in liver fibrosis. It was the first such trial to measure effects on body weight in participants. Semaglutide was responsible for an improvement in liver fibrosis with no acute deterioration in steatohepatitis in 36.8% of recipients, the results showed. In comparison, the placebo group only saw a reduction of 22.4%. This led to an estimated gap of 14.4 percentage points between the two groups. This result was highly statistically significant with a p < .001.
These are pretty remarkable numbers for semaglutide coming out of this trial. Study participants achieved an average body weight reduction of 10.5%, compared to an average 2.0% change in the placebo group. Not surprisingly, the estimated difference in mean body weight change was -8.5 percentage points, emphasizing the effectiveness of the medication.
We tested 534 patients for the presence of steatohepatitis. In 62.9% of those cases, semaglutide resulted in at least resolution of the condition with no progression of fibrosis. The joint resolution of steatohepatitis and improvement in liver fibrosis was detected in 32.7% of the semaglutide arm.
Naga P. Chalasani, MD, a principal investigator of the study, underlined the importance of these findings, saying,
“The results from this study certainly make a case for semaglutide to be the backbone therapy for diabetic or obese patients with MASH and fibrosis.”
Chalasani noted that the majority of patients with MASH and fibrosis (more than 80%) are diagnosed with diabetes or obesity. This emphasizes the need for more timely and effective treatment options for these people.
Philip Newsome, another major player in the research, pointed out that previous studies were unable to demonstrate benefit in liver fibrosis. He feels the results of the ESSENCE trial are very promising. He remarked,
“That study, however, did not show improvement in liver fibrosis, which this study has done.”
He said the results more than achieved the pre-specified thresholds for improvement in liver fibrosis. He noted the unknowns with regard to long-term outcomes.
“The results aligned with expectations in that the impact on liver fibrosis was anticipated — but with some uncertainty, so this study is important in that regard,” said Newsome.
While Chalasani acknowledged the positive findings, she stressed the need for further study. Inequities remain, and we need to look into the larger effects of semaglutide treatment on them. He recommended that more research be conducted. These trials would need to show that semaglutide is beneficial in clinical outcomes beyond histologic improvement in the liver.
“But this may need to be repeated as the published study was underpowered. Outcomes in the ESSENCE trial will help to clarify whether semaglutide will improve clinical outcomes beyond improving liver histology,” he stated.
Newsome posed several critical inquiries regarding future studies:
“Will there be further improvements with longer treatment with semaglutide? What noninvasive tests should we use to determine treatment success? Which patients will benefit from combination treatment?”
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