Renal effects of a sodium‐glucose cotransporter 2 inhibitor, tofogliflozin, in relation to sodium intake and glycaemic status

AIMS: Little is known about whether sodium intake is associated with the clinical effects of SGLT2 inhibitors (SGLT2is); however, SGLT2is may increase urinary sodium excretion. Thus, we investigated the impact of daily sodium intake on the estimated glomerular filtration rate (eGFR) via an SGLT2i, tofogliflozin (TOFO), in patients with type 2 diabetes (T2D). METHODS: Individual‐level data on 775 T2D patients in TOFO Phase 3 trials were analysed. Adjusted changes in variables during 52 weeks of TOFO therapy were compared according to basal daily salt intake (DSI), which was measured based on estimated daily urinary sodium excretion using the Tanaka formula. Multivariable analysis was used to investigate the impact of basal DSI on changes in eGFR at Weeks 4 and 52. RESULTS: Sixty‐six percent of participants were men; mean age, HbA1c, body mass index, eGFR(MDRD) and median DSI were 58.5 years, 8.0%, 25.6 kg/m(2), 83.9 mL/min/1.73 m(2) and 9.3 g/d, respectively. In all participants, eGFR(MDRD) sharply dipped during Week 4, and gradually increased by Week 52, showing a significant increase overall from baseline to Week 52. Multivariable analysis showed that basal DSI and HbA1c levels were independently correlated with eGFR(MDRD) changes at Weeks 4 and 52. Additionally, lower baseline HbA1c and DSI levels were significantly correlated with a greater increase in eGFR(MDRD) at Week 52. CONCLUSIONS: Dietary salt intake, in addition to glycaemic control, correlates with changed eGFR(MDRD) via TOFO. Thus, an appropriate dietary approach to therapy should be considered before treatment of T2D patients with an SGLT2i.