In a propensity-matched real-world cohort of adults with metabolic-associated steatotic liver disease (MASLD), use of tirzepatide was associated with a 70% reduction in major adverse cardiovascular events (MACE), fewer hospitalizations, and greater weight loss over three years compared with use of semaglutide.
“Cardiovascular disease (CVD) is the primary driver of mortality in patients with MASLD, yet pharmacotherapy addressing cardiometabolic risk factors are scarce,” presenting author Himsikhar Khataniar, a third-year internal medicine resident at Allegheny General Hospital, Pittsburgh, Pa., and colleagues wrote in a poster abstract presented during the annual meeting of the American Association for the Study of Liver Diseases. “Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) address weight and hyperglycemia, but dual incretin agonists that also stimulate glucose-dependent insulinotropic polypeptide (GIP) receptors may confer additional benefits. Tirzepatide, the first GLP-1/GIP co-agonist has outperformed semaglutide for weight and glycemic control in clinical trials. However, direct CVD data in MASLD are limited.”
Drawing from the U.S. TriNetX network, the researchers identified adults with an ICD-10 diagnosis of fatty liver disease and at least one metabolic risk factor (diabetes, obesity, hypertension, or dyslipidemia) who first filled a prescription for tirzepatide or semaglutide between January 2015 and December 2021. They excluded individuals with other liver diseases, prior GLP-1 RA use, bariatric surgery, critical-care admission, liver transplantation, previous MACE, or major liver outcomes, and used one-to-one propensity-score matching to balance age, sex, race, body-mass index (BMI), diabetes, hypertension, and dyslipidemia between treatment groups. The primary endpoint was a three-year composite MACE. Secondary endpoints included individual cardiovascular events, acute heart failure, all-cause mortality, all-cause hospitalization, and change in BMI.
Among 15,538 eligible MASLD patients, 1,500 initiated tirzepatide and 14,038 initiated semaglutide; propensity matching produced 1,497 patients in each cohort with well-balanced baseline characteristics. Over three years, tirzepatide was associated with a lower incidence of MACE compared with semaglutide (1.3% vs 4.1%). Myocardial infarction occurred less frequently with tirzepatide (0.7% vs 2%), while rates of stroke and acute heart failure were numerically lower but not statistically different compared with semaglutide. Tirzepatide also reduced all-cause hospitalization (21.3% vs 30.7%), while mortality remained low in both groups (≤0.67%). BMI reduction was greater with tirzepatide (–4.1 vs –2.2 kg/m²).
“These findings suggest that dual GLP-1/GIP receptor agonism provides superior cardiometabolic protection compared to GLP-1 monotherapy,” the authors concluded. “Prospective head-to-head clinical trials are warranted to validate these cardiovascular and liver-related benefits and to guide optimal therapeutic strategies for this high-risk population.”
They did not report having conflicts of interest.
Source: AASLD