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Lilly's Tirzepatide Shows Promise in MASH Treatment, Achieves Notable Results in Phase 2 Study | iPharmaCenter

Eli Lilly has revealed promising results from the SYNERGY-NASH study, a phase 2 clinical trial assessing tirzepatide's efficacy in treating metabolic dysfunction-associated steatohepatitis (MASH) with stage 2 or 3 fibrosis. This study included 190 adult participants, both with and without type 2 diabetes.

The trial's findings were presented at the European Association for the Study of the Liver (EASL) Congress 2024 and simultaneously published in The New England Journal of Medicine. Results demonstrated that tirzepatide significantly outperformed the placebo in resolving MASH.

Specifically, 51.8% of participants on a 5 mg dose, 62.8% on a 10 mg dose, and 73.3% on a 15 mg dose achieved MASH resolution without worsening fibrosis, compared to just 13.2% of those on the placebo after 52 weeks, meeting the study’s primary endpoint.

Regarding the secondary endpoint, the study showed that 59.1%, 53.3%, and 54.2% of participants taking 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, experienced a one-stage or greater improvement in fibrosis without a worsening of MASH. This is in comparison to 32.8% of participants on the placebo. Additionally, tirzepatide was linked to improvements in body weight, liver injury markers, and biomarkers associated with liver fat, inflammation, and fibrosis. While the phase 2 trial was not intended to definitively prove fibrosis improvement, these results suggest a meaningful clinical benefit across all dosages.


5 mg


10 mg

Tirzepatide 15 mg


At week 52, MASH resolution with worsening of fibrosis





>1 stage decrease in fibrosis stage without worsening of MASH





Tirzepatide's safety profile in the SYNERGY-NASH study aligned with previous findings from the SURMOUNT and SURPASS trials. The most frequent side effects were gastrointestinal issues, including nausea, diarrhea, decreased appetite, constipation, and weight loss, mostly mild to moderate in severity.

Tirzepatide is a once-weekly injectable medication that targets both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptors. These receptors play a crucial role in appetite regulation, and tirzepatide's dual action helps reduce food intake and influence fat metabolism. Beyond MASH, tirzepatide is being explored as a treatment for obesity, heart failure with preserved ejection fraction (HFpEF), obstructive sleep apnea (OSA), and chronic kidney disease (CKD), among other conditions.

The U.S. FDA approved tirzepatide as Mounjaro® for improving glycemic control in adults with type 2 diabetes in May 2022. It was also approved as Zepbound® for adults with obesity or overweight with a BMI of 27 kg/m2 or greater and related comorbidities in November 2023. Both medications are intended to complement diet and exercise.

The SYNERGY-NASH trial was a multicenter, double-blind, randomized, placebo-controlled study, examining tirzepatide's effectiveness and safety at different doses. Participants were randomized to receive either 5 mg, 10 mg, 15 mg of tirzepatide, or a placebo, administered weekly for 52 weeks. The trial's main goal was to assess MASH resolution without worsening fibrosis, with secondary goals focusing on fibrosis improvement without worsening MASH.



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