Effects of GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists on inflammatory and metabolic biomarkers in Type 2 diabetes: a systematic review and meta-analysis

Abstract

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and dual GIP/GLP‐1 receptor agonists improve cardiovascular outcomes in type 2 diabetes mellitus (T2DM), but their effects on inflammatory and oxidative biomarkers are not fully defined. Materials and Methods We searched PubMed, Ovid MEDLINE, Scopus, Web of Science and the Cochrane Library from inception to 19 February 2026 for randomised controlled trials (RCTs) in adults with T2DM comparing a GLP‐1RA or dual GIP/GLP‐1 agonist with placebo or active therapy, and reporting C‐reactive protein (CRP or high‐sensitivity CRP [hs‐CRP]), interleukin‐6 (IL‐6), tumour necrosis factor‐α (TNF‐α), monocyte chemoattractant protein‐1 (MCP‐1), malondialdehyde (MDA) or adiponectin. Random‐effects meta‐analyses were conducted using standardised mean differences (SMDs). Results Forty‐one RCTs were included. GLP‐1RAs significantly reduced CRP/hs‐CRP (27 studies, 1991 participants; SMD −0.37, 95% CI −0.59 to −0.14) and MDA (3 studies, 272 participants; SMD −0.98, 95% CI −1.65 to −0.30), and increased adiponectin (16 studies, 1327 participants; SMD 0.30, 95% CI 0.13 to 0.46). Pooled effects on IL‐6 (17 studies, 1068 participants; SMD −0.14, 95% CI −0.37 to 0.10), TNF‐α (16 studies, 1164 participants; SMD −0.25, 95% CI −0.61 to 0.12) and MCP‐1 (7 studies, 450 participants; SMD −0.27, 95% CI −0.58 to 0.03) were not statistically significant, although MCP‐1 decreased in sensitivity analyses. Across biomarkers, heterogeneity was moderate to high. Two tirzepatide RCTs (562 participants) showed a significant reduction in IL‐6 (SMD −0.28, 95% CI −0.47 to −0.09) and a non‐significant trend towards lower CRP/hs‐CRP. Conclusions In adults with T2DM, incretin‐based therapies consistently lower CRP/hs‐CRP, reduce oxidative stress (MDA) and increase adiponectin, while effects on IL‐6 and TNF‐α are more variable. These data support a selective anti‐inflammatory and metabolic regulatory profile of GLP‐1–based therapy, but heterogeneity and limited data for some biomarkers warrant cautious interpretation and further mechanistic studies. Trial Registration: PROSPERO number: CRD420261321430