Systematic Review of Tirzepatide’s Dual Action on Glycemic Control and Hepatic Biomarkers in Adults with Type 2 Diabetes

Abstract

Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a promising therapeutic agent for type 2 diabetes mellitus (T2DM), with potential benefits extending beyond glycemic control. This systematic review evaluates evidence from nine clinical studies assessing tirzepatide’s impact on both glycemic parameters and hepatic biomarkers in adults with T2DM. The findings consistently demonstrate that tirzepatide, particularly at doses of 10 mg and 15 mg, significantly reduces serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), keratin-18 (K-18), and procollagen III (Pro-C3), while increasing adiponectin concentrations. These changes suggest a beneficial effect on hepatocellular injury, fibrosis, and inflammation, markers typically associated with non-alcoholic steatohepatitis (NASH). Importantly, the hepatic improvements observed were not fully explained by weight loss or HbA1c reduction, indicating potential direct hepatometabolic effects. Although histological validation is lacking, the biomarker data highlight tirzepatide’s promise as a dual-action agent for T2DM patients with coexisting metabolic liver disease. Further prospective trials with biopsy-confirmed NASH populations are warranted to substantiate these findings.