The effect of GLP-1 receptor agonists on circulating inflammatory markers in type 2 diabetes patients: A systematic review and meta-analysis

Diabetes Obes Metab. 2025 Jul;27(7):3607-3626. doi: 10.1111/dom.16366. Epub 2025 Apr 15.

Abstract

Aim: To investigate whether the antidiabetic agent glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can exert anti-inflammatory effects while lowering blood glucose, we performed a meta-analysis and systematic review.

Methods: We searched 4 online databases (Medline, Embase, Cochrane Library and the Web of Science) for randomised controlled trials (RCTs) that examined changes after GLP-1RAs intervention in commonly accepted biomarkers of inflammation: C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1(MCP-1) and advanced glycation end products (AGEs).

Results: This meta-analysis included 52 eligible RCTs (n = 4734) with a median follow-up of 24 weeks, a mean age of 54.13 years, 44.46% females, body mass index (BMI) 29.80 kg/m2, glycated haemoglobin (HbA1c) 8.28% and diabetes duration 7.27 years. GLP-1 RAs treatment, compared to placebo or conventional diabetes therapies (including oral medicine and insulin), resulted in significant reductions in CRP, TNF-α, IL-6, IL-1β and leptin (standard mean difference [SMD] -0.63 [-1.03, -0.23]; SMD -0.92 [-1.57, -0.27]; SMD -0.76 [-1.32, -0.20], SMD -3.89 [-6.56, -1.22], SMD -0.67 [-1.09, -0.26], respectively), as well as significant increases in adiponectin (SMD 0.69 [0.19, 1.19]).

Conclusions: Our meta-analysis demonstrates that GLP-1 RAs exert significant anti-inflammatory effects in patients with T2DM. Our findings provide important insights that may guide the therapeutic application of GLP-1 RAs and inform the development of related therapies.

Keywords: CRP; GLP‐1 RAs; IL‐6; glucagon‐like peptide‐1 receptor agonists; inflammation; meta‐analysis.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Female
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Inflammation* / blood
  • Inflammation* / drug therapy
  • Randomized Controlled Trials as Topic

Substances

  • Glucagon-Like Peptide-1 Receptor Agonists
  • Biomarkers
  • Hypoglycemic Agents
  • C-Reactive Protein