A systematic review examining the effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on biomarkers of inflammation and oxidative stress

Aims: 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. Methods: A search of Medline, Embase, Web of Science, and The Cochrane Library was performed examining changes in selected clinical biomarkers for inflammation: c-reactive protein (CRP), adiponectin, interleukin-6 (IL6), tumour necrosis factor-alpha (TNF-alpha), and oxidative stress: 8-iso-prostaglandin F2 alpha (8-iso-PGF2 alpha) and 8-hydroxy-20-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. Results: A total of 23 (15 randomised, 8 observational) heterogeneously-designed clinical studies were identified (1654 patients, 24 weeks median follow-up). Consistent reductions were observed for CRP (10/12 studies), IL6 (5/5 studies), TNF alpha (3/4 studies), 8-iso-PGF2v (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. Conclusions: There 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. (C) 2020 Published by Elsevier B.V.