Tirzepatide vs SGLT2 Inhibitors in MASLD Across Disease Stages

Among adults with type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD), starting tirzepatide was associated with fewer major adverse liver outcomes (MALO) and cardiovascular events than starting a sodium-glucose cotransporter 2 (SGLT2) inhibitor, according to research presented by Mohammad Alabbas, MD, at The Liver Meeting 2026 in Denver, Colorado.

Alabbas, a research fellow in the hepatology section of the Department of Gastroenterology at Cleveland Clinic, told HCP Live that type 2 diabetes is a key risk factor for MASLD and that both drug classes are widely used in this population. Patients with compensated cirrhosis, however, are underrepresented in clinical trials, and clinicians sometimes prescribe these agents off label for them.

How Did Outcomes Differ by Disease Stage?

Using TriNetX data from 110 health care organizations, investigators propensity score matched adults who initiated tirzepatide (Mounjaro) or an SGLT2 inhibitor after June 2022 and divided them into noncirrhotic and compensated cirrhosis cohorts. In noncirrhotic MASLD or metabolic dysfunction-associated steatohepatitis (MASH), tirzepatide was associated with lower MALO at 1 year (0.8% vs 1.4%; RR, 0.57) and 3 years (1.6% vs 2.3%; RR, 0.67), along with lower rates of major adverse cardiovascular events (MACE), mortality, and incident cirrhosis.¹

In compensated cirrhosis (816 matched pairs), tirzepatide was associated with lower MACE at both time points and lower 3-year MALO (8.3% vs 11.5%; RR, 0.72), with no excess acute kidney injury or ascites-related outcomes.¹

What Do the Findings Mean for Practice?

The results add real-world context to randomized data, such as the phase 2 SYNERGY-NASH trial, in which tirzepatide improved MASH resolution compared with placebo.² Still, Alabbas cautions that the observational design cannot answer definitive questions, including how tirzepatide compares with semaglutide.

“We need prospective studies,” he said.

Watch the full interview to hear Alabbas explain why the study focused on disease stage and how the findings could inform future clinical trials.

Alabbas has no relevant disclosures.

References

1. Alabbas M, Alnounou A, Alhusen A, et al. Stage-stratified comparative effectiveness of tirzepatide versus SGLT2 inhibitors in type 2 diabetes (T2DM) on major adverse liver outcomes (MALO) and major adverse cardiovascular events (MACE) with MASLD/MASH. Presented at: The Liver Meeting 2026; November 5-9, 2026; Denver, CO.
2. Loomba R, Hartman ML, Lawitz EJ, et al. Tirzepatide for metabolic dysfunction–associated steatohepatitis with liver fibrosis. N Engl J Med. 2024;391(4):299-310. doi:10.1056/NEJMoa2401943