Comparison of the efficacy of antidiabetic agents in type 2 diabetes with MASLD: a network meta-analysis

Front Endocrinol (Lausanne). 2026 Jan 7:16:1659740. doi: 10.3389/fendo.2025.1659740. eCollection 2025.

Abstract

Objective: To evaluate and compare the efficacy of different antidiabetic agents in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM).

Methods: We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science for relevant randomized controlled trials up to April 20, 2025. Primary outcomes were alanine aminotransferase (ALT), aspartate aminotransferase (AST), and triglycerides. Secondary outcomes included HDL, LDL, fasting plasma glucose (FPG), body mass index (BMI), and glycated hemoglobin (HbA1c). All statistical analyses were performed using R version 4.5.0.

Results: A total of 21 randomized controlled trials were included, covering 15 antidiabetic agents and involving 1,717 participants. Ertugliflozin was the most effective in reducing ALT and AST levels, followed by pioglitazone and metformin for ALT, and pioglitazone and ipragliflozin for AST. Ertugliflozin also showed favorable effects on triglycerides, BMI, HDL, LDL, and liver stiffness. However, most comparisons did not reach statistical significance.

Conclusion: Ertugliflozin appears to be among the most effective treatment options for improving liver function and metabolic parameters in patients with MASLD and T2DM. However, these findings should be interpreted with caution, and further high-quality studies are needed to confirm these results. Ertugliflozin may be the most effective option for improving liver function and metabolic parameters in patients with MASLD and T2DM. Further studies are needed to confirm these findings.

Keywords: MASLD; antidiabetic agents; liver; network meta-analysis; type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Network Meta-Analysis

MeSH terms

  • Blood Glucose
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Blood Glucose
  • Hypoglycemic Agents