Efficacy and safety of SGLT2 inhibitors in patients with heart failure according to kidney function: a systematic review and meta-analysis

Introduction and objectives: This study aimed to evaluate the efficacy and safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors throughout the spectrum of kidney function in patients with heart failure (HF). Methods: This meta-analysis included randomized controlled trials comparing SGLT2 inhibitors with placebo in patients with HF stratified by renal function. Literature from inception to June 8, 2024 was searched. The primary outcome was a composite of cardiovascular death or HF events. Results: Five trials were identified, comprising 21 204 patients (10 605 in the SGLT2 inhibitor group and 10 599 in the placebo group) who were randomized and followed up for a weighted median duration of 1.8 years. When patients were classified by estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m², SGLT2 inhibitors reduced the risk of the primary outcome irrespective of kidney function (RR, 0.81; 95%CI, 0.75-0.87; P < .01 for eGFR < 60 mL/min/1.73 m²; RR, 0.79; 95%CI, 0.72-0.87; P < .01 for eGFR≥ 60 mL/min/1.73 m²; test for subgroup differences P = .75). The beneficial impact of SGLT2 inhibitors was consistently observed when patients were further subclassified by eGFR values of 20-30, 30-45, 45-60, and > 60 mL/min/1.73 m² (test for subgroup differences, P = .54). Early eGFR decline showed a differential impact with increased risk only in the placebo subgroup (RR, 1.30; 95%CI, 1.15-1.47; P < .01), but not in the SGLT2 inhibitor subgroup (RR, 0.99; 95%CI, 0.86-1.13; P = .84) (test for subgroup differences, P < .01). Conclusions: SGLT2 inhibitor therapy is safe and effective throughout the spectrum of kidney function and regardless of the initial decline in kidney function in patients with chronic HF. Registered at PROSPERO: CRD42024565218.