261 Impact of Baseline Kidney Function on Sglt2 Inhibitor Effects on Renal and Heart Failure Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce renal and heart failure (HF) events in people with and without diabetes. Although their glycemic efficacy is dependent on kidney function, it remains unclear to what extent baseline kidney function influences the magnitude of SGLT2i cardiorenal effects. Methods We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials testing the effects of SGLT2i on renal and CV outcomes (PROSPERO registration number CRD42022325976). Efficacy outcomes, stratified by five estimated glomerular filtration rate (eGFR) categories, included progression of renal disease (as defined in each trial), a composite HF outcome (defined as CV death or hospitalization/urgent visit for HF), and all-cause mortality. Results Eleven trials testing five SGLT2i (empagliflozin, dapagliflozin, canagliflozin, ertugliflozin and sotagliflozin) in 77,541 participants were included. The majority of participants (39.8%) had eGFR values between 60 and 90 ml/min/1.73m2, with only 1.3% having advanced kidney disease (eGFR between 20 and 30 ml/min/1.73m2). Overall, SGLT2i reduced the risk of renal disease progression by 41% (HR 0.59, 95%CI 0.54–0.65, p<0.001) and the risk of HF outcomes by 22% (HR 0.78, 95%CI 0.73–0.83, p<0.001). Meta-regression analyses showed a significant direct relationship between baseline eGFR and the magnitude of SGLT2i renal protection (p=0.040). The greatest relative risk reduction was in participants with eGFR values ≥90 ml/min/1.73m2 (HR 0.43, 95%CI 0.32–0.58) and the smallest was in those with an eGFR between 30 and 45 ml/min/1.73m2 (HR 0.64, 95%CI 0.55–0.76). Conversely, the HF outcome showed a non-significant trend to greater benefit in participants with lower eGFR categories (p=0.086). The greatest relative risk reduction was in those with an eGFR between 20 and 30 ml/min/1.73m2 (HR 0.68, 95%CI 0.48–0.96, p=0.026) and the smallest was in those with an eGFR ≥90ml/min/1.73m2 (HR 0.87, 95%CI 0.56–1.35, p=0.52). Conclusions SGLT2i reduce risk of renal disease progression and HF outcomes for all eGFR subgroups. However, the opposite trends for the influence of baseline kidney function between renal and HF outcomes suggest different SGLT2i mechanisms for renal and cardiac protection.