Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) improve biomarkers of inflammation and oxidative stress: A systematic review and meta-analysis of randomised controlled trials.

AIMS Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) have cardiorenal protective properties in patients with type 2 diabetes (T2DM) that are not fully understood. Inflammation and oxidative stress play a role in the pathogenesis of T2DM and its associated cardiorenal complications. Anti-inflammatory and antioxidant properties may contribute towards explaining the beneficial effects of GLP-1RAs. This meta-analysis and systematic review examines the effects of GLP-1RAs on clinical biomarkers of inflammation and oxidative stress. METHODS Medline, Embase and The Cochrane Library were searched for randomised controlled trials (RCTs) that examined changes with GLP-1RAs in a priori selected biomarkers of inflammation:- c-reactive protein (CRP), adiponectin, tumour necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL6), leptin; and oxidative stress:- malondialdehyde (MDA), 8-iso-prostaglandin F2α (8-iso-PGF2α), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). (PROSPERO: CRD42020182116) RESULTS: We included 40 eligible RCTs (n=6749) with a median follow-up of 6 months, mean participant age of 53.1 years, 56.3% females, HbA1c 7.24%, body mass index (BMI) 28.8kg/m2 and diabetes duration of 7.46 years. Analysis of GLP-1RAs versus standard diabetes therapies or placebo revealed significant reductions in CRP, TNFα and MDA, and significant increases in adiponectin for (mean difference -0.54mg/L [-0.75, -0.34]; standard mean difference (SMD) -0.39 [-0.62, -0.15]; SMD -0.84 [-1.61, -0.06] and SMD 0.30 [0.12, 0.49], respectively). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. HOMA-IR was also significantly correlated with a reduction in CRP, but glycated haemoglobin was not. CONCLUSIONS There is strong evidence supporting clinically relevant anti-inflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and in the development of medications seeking to target the cardioprotective properties of GLP-1RAs. This article is protected by copyright. All rights reserved.