Effects of Linagliptin on Liver Enzymes in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Type 2 diabetes mellitus (T2DM) is often linked to metabolic dysfunction-associated steatotic liver disease (MASLD), a metabolic liver condition defined by excessive lipid deposition within hepatocytes and is frequently accompanied by increased circulating liver enzyme levels. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as linagliptin, may exert pleiotropic effects on hepatic metabolism; however, their effects on liver enzyme profiles remain uncertain. This systematic review and meta-analysis aimed to evaluate the impact of linagliptin on liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), in patients with T2DM. A systematic literature search was performed across five electronic databases up to 11 May 2026 following the PRISMA 2020 guidelines. Randomized controlled trials and cohort studies were included, and pooled mean differences (MDs) were calculated using random-effects models. Eight studies involving 1262 participants were analyzed. Linagliptin was associated with a modest reduction in AST (MD −1.58 U/L, 95% CI −2.85 to −0.31) with low heterogeneity, whereas the change in ALT was not statistically significant (MD −1.86 U/L, 95% CI −4.14 to 0.42), and substantial heterogeneity was observed. No significant effects were observed for GGT, while evidence for ALP was limited to a single study and was insufficient to determine the effect of linagliptin. Overall, linagliptin demonstrated limited and inconsistent effects on liver enzyme profiles.