Aim: To conduct a meta-analysis and systematic review to examine the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on clinical biomarkers of inflammation and oxidative stress in patients with type 2 diabetes.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 (TNFα), plasminogen activator inhibitor-1, interleukin-6, leptin; and of oxidative stress: malondialdehyde (MDA); 8-iso-prostaglandin F2α; and 8-hydroxy-2 0 -deoxyguanosine (8-OHdG). Results: We included 40 eligible RCTs (n = 6749) with a median follow-up of 6 months, a mean participant age of 53.1 years, 56.3% females, glycated haemoglobin (HbA1c) 55.6 mmol/mol, body mass index 28.8 kg/m 2 and diabetes duration 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 À0.54 mg/L [À0.75, À0.34]; standard mean difference [SMD] À0.39 [À0.62, À0.15]; SMD À0.84 [À1.61, À0.06] and SMD 0.30 [0.12, 0.49], respectively [95% confidence intervals]). Systolic blood pressure decreased significantly and was significantly and strongly correlated with a reduction in CRP. Homeostatic model assessment of insulin resistance was also significantly correlated with a reduction in CRP, but HbA1c was not. Conclusions: There is strong evidence supporting clinically relevant antiinflammatory and antioxidant effects of GLP-1RAs. This may be used to guide future targeted clinical use of GLP-1RAs and the development of medications seeking to target the cardioprotective properties of GLP-1RAs. * Jonathan J. H. Bray and Harri Foster-Davies are co-first authors.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have a protective cardiorenal effect in type 2 diabetes. This systematic review examines the effects of SGLT2is on clinical biomarkers of inflammation and oxidative stress. MethodsA search of Medline, Embase, Web of Science, and The Cochrane Library was performed examining changes in selected clinical biomarkers for inflammation: creactive protein (CRP), adiponectin, interleukin-6 (IL6), tumour necrosis factor-alpha (TNF-α), and oxidative stress: 8-iso-prostaglandin F2α (8-iso-PGF2α) and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Quality of evidence was evaluated using the GRADEpro tool and risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools. ResultsA total of 23 (15 randomised, 8 observational) heterogeneously-designed clinical studies were identified (1,654 patients, 24 weeks median follow-up). Consistent reductions were observed for CRP (10/12 studies), IL6 (5/5 studies), TNFα (3/4 studies), 8-iso-PGF2α (3/4 studies) and 8-OHdG (2/2 studies), and a consistent increase in adiponectin (6/8 studies). Change in serum CRP following SGLT2is appear to be independent of change in HbA1c and other study design and clinically relevant variables. ConclusionsThere is heterogeneous, yet consistent data supporting the beneficial effects of SLGT2is on inflammatory and oxidative stress. Change in serum CRP appears to be independent of change in HbA1c.

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