Effect of GLP-1 RA and SGLT2I on Biomarkers of Oxidative Stress in T2DM

Huannan Wei, Lingyu Ye, Mingli Li, Shengzhu Huang, Zengnan Mo
Journal of the Endocrine Society, Volume 9, Issue 8, August 2025, bvaf075
https://doi.org/10.1210/jendso/bvaf075

Abstract

Objective

To evaluate the effects of GLP-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2Is) on oxidative stress biomarkers in adults (>18 years) with type 2 diabetes mellitus (T2DM), a meta-analysis of randomized controlled trials (RCTs) was conducted.

Methods

We searched PubMed, Embase, the Cochrane Library, and China National Knowledge Infrastructure from January 1, 2000, to August 15, 2024. Biomarkers included peroxidants (malondialdehyde [MDA] and others) and antioxidants (superoxide dismutase), glutathione peroxidase, and total antioxidant capacity).

Results

Among 1976 patients with T2DM in 26 RCTs of GLP-1 RAs and 1124 patients with T2DM in 17 RCTs of SGLT2Is, significant reductions in serum MDA concentrations (−1.75; CI, −2.38 to −1.12; P < .001; −.88; CI: −1.62 to −.13; P = .020, respectively) and significant increases in serum superoxide dismutase concentrations (1.75; CI, 1.12–2.37; P < .001; 1.25; CI, .51–1.98; P < .001, respectively) and glutathione peroxidase concentrations (1.78; CI, .8–2.75; P < .001; not significant for SGLT2Is: 0.87, CI, −.22 to 1.96; P = .12) were observed compared to diabetes treatment or placebo groups. A positive correlation was found between serum MDA and body mass index in patients with T2DM treated with GLP-1 RAs (r = 0.791, P < .05) or SGLT2Is (r = 0.924, P < .05).

Conclusion

This meta-analysis provides clear evidence of clinically relevant significant antioxidative stress effects of GLP-1 RAs and SGLT2Is, potentially guiding their precise clinical application.

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