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General Endocrinology

MON-859 - Efficacy of Dual GIP/GLP-1 Agonists in MASLD/MASH in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Hepatic Outcomes

Monday, June 15, 2026
9:00 AM - 2:00 PM CT


Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is highly prevalent among patients with type 2 diabetes mellitus (T2DM), a group at increased risk of progression to metabolic dysfunction-associated steatohepatitis (MASH) and advanced fibrosis. In this context, dual GIP/GLP-1 agonists have emerged as a promising strategy due to their metabolic effects. This study aimed to assess their efficacy in histological and imaging-based hepatic outcomes in patients with T2DM.

Methods: This was a systematic review and meta-analysis of randomized trials (phase 2 and 3) and post hoc analyses, conducted in accordance with PRISMA guidelines. A total of 143 articles were identified in PubMed and Embase, and screening by two independent reviewers using Rayyan resulted in 6 studies included in the final analysis. Eligible studies evaluated tirzepatide compared with placebo, basal insulin, or isolated glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The primary outcomes included histological resolution of MASH and reduction in liver fat by MRI-PDFF. Statistical synthesis, performed in R, used a random-effects model to calculate RR and MD, with a significance level of 5%.

Results: This review included 6 studies with follow-up ranging from 26 to 52 weeks in multicenter populations of adults with T2DM and MASLD/MASH (confirmed steatosis and F2–F3 fibrosis). Tirzepatide (5, 10, and 15 mg/week) was compared with GLP-1 receptor agonists, insulin degludec, and placebo. The analysis showed consistent superiority of tirzepatide across all assessed settings. Histologically, tirzepatide achieved higher rates of MASH resolution both versus placebo (SYNERGY-NASH: 44–62% vs. 10%) and versus a GLP-1 agonist alone (Ali A., 2025: 50% vs. 22%). In imaging outcomes (MRI-PDFF), it reduced liver fat by up to 47.1% compared with 11.2% with insulin degludec (SURPASS-3), and also showed improvements in liver stiffness (Kawano T., 2025). Despite high heterogeneity (high I²), the effect remained consistently favorable to the intervention.

Conclusion: In the treatment of MASLD/MASH in patients with T2DM, dual GIP/GLP-1 agonists demonstrated superior efficacy in improving hepatic outcomes compared with placebo, basal insulin, and GLP-1 receptor agonists. A higher rate of MASH resolution without fibrosis progression was observed, along with a consistent reduction in hepatic steatosis, positioning tirzepatide as a promising therapeutic strategy in this clinical context.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*