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

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/m 2 , 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.