Baseline eGFR, albuminuria and renal outcomes in patients with SGLT2 inhibitor treatment: an updated meta-analysis

Aims: To elucidate the association between baseline renal characteristics and the disparities in renal outcomes among patients with SGLT2i treatment. Methods: Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were searched from inception to November 2022. Event-driven randomized controlled trials of SGLT2i with reports of renal outcomes were included. Sensitivity analyses of prespecified eGFR and UACR subgroups were conducted. Results: Generally, compared with placebo, the use of SGLT2i was associated with improved renal prognosis (HR = 0.64, 95%CI 0.59–0.70). The magnitude of risk reductions in composite renal outcomes between SGLT2i versus placebo was comparable among different eGFR stratifications (normal renal function: HR = 0.49, 95%CI 0.31–0.79; mild renal impairment: HR = 0.57, 95%CI 0.48–0.68; moderate renal impairment: HR = 0.70, 95%CI 0.63–0.78; severe renal impairment: HR = 0.72, 95%CI 0.62–0.84; P for subgroup difference = 0.09). However, renal benefits seemd to be more prominent in normal to mildly increased albuminuria stratum (HR = 0.51, 95%CI 0.39–0.66) and severely increased albuminuria stratum (HR = 0.57, 95%CI 0.47–0.68), when compared with moderately increased albuminuria stratum (HR = 0.79, 95%CI 0.65–0.96; P for subgroup difference = 0.01). Conclusions: Generally, the use of SGLT2i was consistently associated with decreased risk of renal events in all prespecified eGFR and albuminuria spectrums, even in patients with substantial renal impairment. The renal benefits of SGLT2i seemed to be independent of baseline eGFR, while the risk reduction in renal events was more profound among patients with mildly increased albuminuria or severely increased albuminuria.