EFFICACY AND SAFETY OF DUAL GLP-1/GIP RECEPTOR AGONISTS FOR GASTROINTESTINAL AND HEPATIC OUTCOMES IN ADULTS WITH OBESITY AND TYPE 2 DIABETES: A SYSTEMATIC REVIEW

Abstract

Objective: To evaluate the efficacy and safety of dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonism for gastrointestinal tolerability and hepatic outcomes in adults with obesity and type 2 diabetes. Study design: Systematic review of randomized controlled trials, prespecified imaging sub studies and recent meta-analyses. Place and duration of the study: Global evidence was reviewed between  February 2025 to may 2026. Methodology: MEDLINE/PubMed was searched for tirzepatide or dual GIP/GLP-1 agonism combined with gastrointestinal, liver, MASLD, MASH or NAFLD outcomes. Adult randomized studies and quantitative syntheses were eligible. Overlapping reports were identified by trial programme and were not pooled as independent participants. Published effects were synthesized without recalculation. Results: The search identified 797 records and 24 focused reports were included. In SURPASS-3 MRI 296 participants had a baseline mean liver fat content of 15.71% ± 8.93%. At week 52 pooled tirzepatide 10/15 mg reduced liver fat by −8.09% ± 0.57 compared with −3.38% ± 0.83 with insulin degludec; estimated treatment difference −4.71% (95% CI −6.72 to −2.70, p<0.0001). In SYNERGY-NASH 190 participants were randomized. MASH resolution without worsening fibrosis occurred in 10% with placebo and 44%, 56% and 62% with tirzepatide 5, 10 and 15 mg (p<0.001 for each comparison). A 10-trial meta-analysis involving 6,836 participants reported dose-dependent gastrointestinal adverse events of 39% (95% CI 35–43), 46% (95% CI 42–49) and 49% (95% CI 38–60) at 5, 10 and 15 mg. Conclusion: Tirzepatide improves liver fat and MASH activity and may improve fibrosis. Gastrointestinal adverse events are frequent, dose-dependent and usually mild to moderate. Gradual escalation and monitoring for dehydration, gallbladder disease and persistent symptoms are required.