EFEITOS DA TIRZEPATIDA SOBRE OS DESFECHOS GASTROINTESTINAIS E HEPÁTICOS: REVISÃO SISTEMÁTICA DAS EVIDÊNCIAS CLÍNICAS E MECANISMOS ENVOLVIDOS.

ABSTRACT Metabolic dysfunction–associated fatty liver disease (MAFLD) and its progressive form, metabolic dysfunction–associated steatohepatitis (MASH), represent major clinical challenges due to their high global prevalence and the absence of approved pharmacological therapies. Tirzepatide, a dual agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, has demonstrated superior metabolic effects compared with isolated incretin-based therapies, with potential hepatic and gastrointestinal benefits. This systematic review aimed to synthesize the available clinical evidence on the effects of tirzepatide on hepatic and gastrointestinal outcomes and to discuss the underlying pathophysiological mechanisms. A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, Embase, Web of Science, Cochrane Library and ClinicalTrials.gov, including studies published between 2018 and 2025, in accordance with PRISMA 2020 guidelines. Twenty studies comprising 10,914 participants were included. Tirzepatide was associated with significant and dose-dependent reductions in liver fat content assessed by MRI-PDFF, consistent improvements in liver enzymes, and high rates of steatohepatitis resolution, with preliminary evidence of fibrosis regression. Gastrointestinal adverse events were common but predominantly mild to moderate, transient and dose-dependent, with low treatment discontinuation rates. In conclusion, tirzepatide demonstrates a favorable hepatic efficacy and gastrointestinal safety profile, with benefits extending beyond weight loss alone, likely mediated through modulation of the gut–liver–metabolic axis.