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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.

Mehmet Kanbay·Ermeena Shah·Rama AlShiab·Lasin Ozbek·Sedat Ay·Aladin Rustamov·Adrian Covic·Francesca Mallamaci·Carmine Zoccali
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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.

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HumansDiabetes Mellitus, Type 2BiomarkersGlucagon-Like Peptide-1 Receptor AgonistsGastric Inhibitory PolypeptideC-Reactive ProteinInflammationHypoglycemic AgentsInterleukin-6Randomized Controlled Trials as TopicTumor Necrosis Factor-alphaMalondialdehydeAdiponectinOxidative StressChemokine CCL2C‐reactive proteinadiponectinglucagon‐like peptide‐1 receptor agonistsinflammationinterleukin‐6oxidative stresstirzepatidetype 2 diabetesJournal ArticleSystematic ReviewMeta-Analysis

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Mehmet Kanbay, Ermeena Shah, Rama AlShiab, Lasin Ozbek, Sedat Ay, Aladin Rustamov, Adrian Covic, Francesca Mallamaci, Carmine Zoccali. 2026-07-14. 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.. https://doi.org/10.1111/dom.71106

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Biomarkers subjectDiabetes Mellitus, Type 2 subjectHumans subjectInterleukin-6 subjectJournal Article subjectJournal Article; Systematic Review; Meta-Analysis resourceMeta-Analysis subjectOxidative Stress subjectSystematic reviews studyinflammation subject

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