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Effect of GLP-1 RA and SGLT2I on Biomarkers of Oxidative Stress in T2DM: A Systematic Review and Meta-analysis

Huannan Wei1,2, Lingyu Ye1,2, Mingli Li1

  • 1Center for Genomic and Personalized Medicine, Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.

Journal of the Endocrine Society
|July 3, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) significantly reduce oxidative stress in type 2 diabetes mellitus (T2DM). These medications lower malondialdehyde and increase antioxidant enzymes, offering clinical benefits.

Area of Science:

  • Endocrinology and Metabolism
  • Pharmacology
  • Biochemistry

Background:

  • Oxidative stress is a key contributor to the pathogenesis of type 2 diabetes mellitus (T2DM).
  • Current diabetes treatments aim to improve glycemic control but may also impact oxidative stress pathways.

Purpose of the Study:

  • To systematically evaluate the impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) on oxidative stress biomarkers.
  • To assess the effects of these drug classes in adult patients with T2DM through a meta-analysis of randomized controlled trials (RCTs).

Main Methods:

  • A comprehensive literature search was conducted across major databases (PubMed, Embase, Cochrane Library, CNKI) from January 2000 to August 2024.
  • Included studies focused on RCTs examining GLP-1 RAs or SGLT2Is in T2DM patients.
  • Key oxidative stress biomarkers analyzed included malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC).

Main Results:

  • GLP-1 RAs significantly reduced serum MDA levels (–1.75) and increased serum SOD (1.75) and GPx (1.78) concentrations.
  • SGLT2Is significantly reduced serum MDA levels (–0.88) and increased serum SOD concentrations (1.25), with no significant effect on GPx.
  • A positive correlation was observed between serum MDA and body mass index (BMI) in patients treated with either GLP-1 RAs or SGLT2Is.

Conclusions:

  • This meta-analysis demonstrates significant antioxidant effects of both GLP-1 RAs and SGLT2Is in patients with T2DM.
  • These findings suggest that GLP-1 RAs and SGLT2Is may offer clinically relevant benefits beyond glycemic control by mitigating oxidative stress.
  • The results support the consideration of these agents for their antioxidative properties in the management of T2DM.
Keywords:
GLP-1 receptor agonistsSGLT2 inhibitorsoxidative stresstype 2 Diabetes mellitus

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