Impact of baseline kidney function on the effects of sodium-glucose co-transporter-2 inhibitors on kidney and heart failure outcomes: A systematic review and meta-analysis of randomized controlled trials

Aim: To determine whether the magnitude of the cardiorenal benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2is) varies with baseline kidney function.

Methods: We searched randomized, placebo-controlled trials testing the effects of SGLT2is on renal and cardiovascular outcomes. Efficacy outcomes, stratified by baseline estimated glomerular filtration rate (eGFR) categories, included renal disease progression, a composite heart failure (HF) outcome and mortality.

Results: Thirteen trials testing SGLT2is in 90 402 participants with available eGFR data were included. The risk of bias was judged as low for all trials. SGLT2is reduced the relative risks of renal disease progression by 27% to 57% and of HF outcomes by 13% to 32% across different eGFR categories, with an overall low heterogeneity. Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2is' renal protection (P = .003). The greatest risk reduction was in participants with an eGFR of 90 ml/min/1.73m² or higher (HR 0.43, 95% CI: 0.32-0.58) and the smallest was in those with an eGFR of less than 30 ml/min/1.73m² (HR 0.73, 95% CI: 0.62-0.86, P < .001). Conversely, for HF, the greatest risk reduction was in those with an eGFR of less than 30 ml/min/1.73m² (HR 0.68, 95% CI: 0.48-0.96) and the smallest was in those with an eGFR of 90 ml/min/1.73m² or higher (HR 0.87, 95% CI: 0.56-1.34).

Conclusions: SGLT2is reduce the risk of renal and HF outcomes for all eGFR categories. The greatest benefits in terms of kidney protection may be achieved by early initiation of SGLT2is in people with preserved eGFR. The greatest risk reduction for HF outcomes is observed in people with lower eGFR values.