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In this episode, hosts explore the promise of semaglutide 2.4 mg in improving liver outcomes for MASH in the Phase 3 ESSENCE trial.
Welcome back to Diabetes Dialogue: Technology, Therapeutics, & Real-World Perspectives!
00:00:01 Introduction and Participant Backgrounds
00:01:18 Overview of MASH and Insulin Resistance
00:03:28 Phase 2 and Phase 3 Trials of Semaglutide
00:07:23 Significant Findings and Clinical Implications
00:09:44 Challenges and Future Directions
00:14:50 Mechanism of Action and Weight Loss
00:17:39 Data on Weight Loss and Liver Improvement
00:20:42 Potential for FDA Approval and Future Studies
00:25:04 Conclusion and Final Thoughts
In this episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, hosts Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and codirector of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, break down new Phase 3 data from the ESSENCE trial examining semaglutide 2.4 mg (Wegovy) for metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis.
With results published in The New England Journal of Medicine, hosts are joined by first author Arun J. Sanyal, MD, director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University, to discuss key takeaways from part 1 of the ESSENCE trial, semaglutide’s impact on liver outcomes and weight loss, and what the data could mean for the future of MASH treatment.
Once-weekly semaglutide 2.4 mg significantly improved liver outcomes in patients with metabolic dysfunction–associated steatohepatitis (MASH) and stage 2 or 3 fibrosis, according to findings from the ESSENCE trial.
In part 1 of the ongoing, double-blind, placebo-controlled trial, 800 patients were evaluated at 72 weeks for two primary endpoints: resolution of steatohepatitis without worsening fibrosis, and fibrosis improvement without worsening steatohepatitis. Spanning 253 sites in 37 countries, the full trial enrolled 1197 biopsy-confirmed patients between May 2021 and April 2023.
At the interim analysis, semaglutide achieved both primary endpoints. Resolution of steatohepatitis without fibrosis worsening occurred in 62.9% of patients receiving semaglutide compared with 34.3% in the placebo group (difference, 28.7%; 95% CI, 21.1–36.2; P <.001). Reduction in fibrosis without worsening steatohepatitis was observed in 36.8% of the semaglutide group versus 22.4% with placebo (difference, 14.4%; 95% CI, 7.5–21.3; P <.001).
Secondary outcomes showed combined resolution of steatohepatitis and fibrosis reduction in 32.7% of semaglutide-treated patients versus 16.1% with placebo (difference, 16.5 percentage points; P <.001). Patients on semaglutide also experienced a mean body weight reduction of 10.5% versus 2.0% in the placebo group (difference: −8.5%; P <.001).
While semaglutide was linked to a slight improvement in bodily pain scores on the SF-36, the result did not reach prespecified statistical significance. Adverse events occurred in 86.3% of the semaglutide group and 79.7% of the placebo group, primarily gastrointestinal. Rates of serious adverse events were similar at 13.4% in both groups.
Resmetirom (Rezdiffra) is the only US Food and Drug Administration (FDA)-approved treatment for noncirrhotic MASH. These findings position semaglutide as a potential future option, pending results from the full ESSENCE trial and regulatory review.
Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others.
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