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Hepatic Events Prevention by Antihyperglycemic Therapies and Intervention Comparisons in Type 2 Diabetes: The

Pedro Robson Costa Passos1, Rodrigo Motta2, Valbert Oliveira Costa Filho3

  • 1Center of Research and Drug Development (NPDM), Federal University of Ceará, Fortaleza, Ceará, Brazil.

Diabetes Care
|April 13, 2026
PubMed
Abstract

Insights

Different diabetes drug classes show varying associations with liver health in type 2 diabetes (T2DM) patients. Thiazolidinediones and GLP-1 receptor agonists appear most beneficial for reducing liver complications.

Area of Science:

  • Endocrinology
  • Hepatology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) significantly increases the risk and burden of liver disease.
  • The comparative impact of various antidiabetic drug classes on liver health outcomes is not well understood.

Purpose of the Study:

  • To compare the associations between different antidiabetic drug classes and major adverse liver outcomes (MALOs) in adults diagnosed with T2DM.

Main Methods:

  • A comprehensive literature search was conducted across PubMed, EMBASE, and Cochrane Central Register of Controlled Trials.
  • Included were 46 observational studies with over 7 million participants (N = 7,124,845) evaluating antidiabetic drugs and MALOs.
  • A three-level Bayesian network meta-analysis was employed, reporting outcomes as hazard ratios (HRs) and ranking them by cumulative curve surface area.

Main Results:

  • Thiazolidinediones showed the lowest association with hepatocellular carcinoma incidence.
  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were linked to the lowest risk of liver decompensation.
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors demonstrated the lowest association with cirrhosis, while GLP-1RAs were least associated with variceal bleeding and hepatic encephalopathy.

Conclusions:

  • The risk reduction for liver-specific outcomes varies significantly among different antihyperglycemic drug classes.
  • Current evidence is derived from observational studies, limiting causal inference.
  • Further randomized controlled trials are essential to confirm if these observed associations represent genuine drug effects on liver health.

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