DAY 3: Dual Agonists Increase Cardiometabolic Protection for Patients with Steatotic Liver Disease and Diabetes

New data presented at the 2025 Annual Scientific Meeting of the American College of Gastroenterology in Phoenix, Arizona showed that dual agonist tirzepatide was more effective than semaglutide in improving cardiovascular outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), obesity, and type 2 diabetes. 

“Metabolic dysfunction-associated steatotic liver disease is the expression of metabolic syndrome in the liver,” lead author Basil Jalamneh, MD, an internal medicine resident at Cleveland Clinic's Fairview Hospital, noted during the presentation. “Cardiovascular-related deaths are by far the most common cause of death in this patient population. Prioritizing medications that offer cardioprotective benefit [is important].” 

Glucagon-like peptide 1 (GLP-1) receptor agonists, which were initially developed for the management of type 2 diabetes, have shown promise for the improvement of liver histology and the resolution of steatohepatitis. In August 2025, the U.S. Food and Drug Administration approved injectable semaglutide for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) in adults with moderate-to-advanced liver fibrosis (defined as stages F2 to F3 fibrosis).

While it is not approved specifically for the treatment of MASLD or MASH, dual receptor agonist tirzepatide, which simultaneously targets GLP-1 and gastric inhibitory polypeptide (GIP), may provide an incremental cardiometabolic benefit for this population. A significantly higher percentage of patients treated with tirzepatide over 52 weeks achieved resolution of MASH without worsening of fibrosis compared to the placebo group in the phase 2 SYNERGY-NASH trial, while also experiencing significant reductions in body weight. 

Jalamneh and colleagues designed a retrospective cohort study to compare the efficacy of tirzepatide with that of semaglutide in adults with MASLD or MASH, obesity, and type 2 diabetes. The final analysis included 14,292 patients treated with tirzepatide and the same number of propensity-matched patients treated with semaglutide, selected from the TriNetX research network. The mean follow-up period was approximately 300 days for both groups. 

The assessment of outcomes at 6 months, 1 year, and 2 years after the initiation of treatment showed that tirzepatide was more effective in reducing mortality, hospitalizations, heart failure, and myocardial infarction compared with semaglutide. Tirzepatide also achieved early reductions in weight and blood pressure, as well as early glycemic control. No statistically significant differences were observed between the two groups in terms of stroke. 

“Patients with MASLD who have established coronary artery disease, heart failure, or frequent hospital admissions may have the most meaningful clinical benefit from tirzepatide,” Jalamneh added. “Shared decision-making with patients and insurance coverage should be taken into consideration when prescribing GLP-1 [therapies].”