Tirzepatide Outperforms Semaglutide in Liver Disease and Diabetes Patients
A real-world study links tirzepatide to fewer deaths and hospitalizations among people with MASLD, obesity, and type 2 diabetes.
A large real-world study comparing tirzepatide (Mounjaro, Zepbound) and semaglutide (Ozempic, Wegovy) found that tirzepatide users had lower risks of death, hospitalization, and major heart events in patients with metabolic liver disease, obesity, and diabetes.
Study Details:
Researchers analyzed data from over 43,000 adults across more than 120 health systems to compare two leading incretin-based therapies tirzepatide, a dual GIP/GLP-1 receptor agonist, and semaglutide, a GLP-1 receptor agonist alone. Participants had metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic-associated steatohepatitis (MASH), along with obesity and type 2 diabetes.
The study was presented at the 2025 American College of Gastroenterology meeting.
Methodology:
Using data from the TriNetX global research network, researchers conducted a propensity score–matched, retrospective cohort analysis. Each treatment arm included 21,513 matched patients, balanced by age, sex, and disease severity.
Average age was 57 years; 58–59% were women; mean BMI was around 40. Participants were followed for up to two years to evaluate mortality, cardiovascular, and hospitalization outcomes.
Key Findings:
Compared with semaglutide, tirzepatide was associated with:
25% lower risk of death (HR 0.75, 95% CI 0.62–0.91)
20% lower risk of hospitalization (HR 0.80, 95% CI 0.76–0.85)
18% lower risk of heart attack (HR 0.82, 95% CI 0.72–0.93)
7% lower risk of heart failure (HR 0.93, 95% CI 0.88–0.99)
23% lower risk of heart failure exacerbation (HR 0.77, 95% CI 0.67–0.88)
Researchers noted that benefits appeared early, possibly due to improvements in weight, blood sugar, and blood pressure.
Implications for Practice:
For clinicians treating patients with MASLD or MASH and type 2 diabetes, these findings reinforce tirzepatide’s potential as a comprehensive metabolic therapy that addresses not only weight and glycemic control but also liver and cardiovascular outcomes.
However, experts caution that the study’s retrospective design and short follow-up period mean results should be interpreted carefully. Randomized trials are needed to confirm causality.