Effects of SGLT-2 Inhibitors on Plasma Concentrations and Renal Clearance of the Risk Marker Trimethylamine-N-Oxide in Patients With Type-2 Diabetes

Background

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have become a key drug class in the treatment of Type 2 diabetes (T2D) due to their effectiveness in blood sugar control, but also for many other clinical indications because of beneficial effects on cardiovascular diseases and mortality. Therefore, the findings of a secondary analysis of the recent EMMY trial, in which acute myocardial infarction patients treated with empagliflozin had higher trimethylamine-N-oxide (TMAO) serum levels compared to placebo, were unexpected, as high TMAO concentrations in blood have previously been linked to adverse cardiovascular and mortality outcomes. In light of this, the aim of our study was to explore the effects of the SGLT-2 inhibitors empagliflozin and dapagliflozin on plasma concentrations and renal clearance (ClR) in a T2D patient setting.