A placebo-adjusted effect of the initial eGFR decline following SGLT-2 inhibitor initia-tion: a systematic review and meta-analysis.

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are pivotal in managing heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus. While their beneficial impact is well-established, the initial decline in estimated glomerular filtration rate (eGFR) at the start of SGLT-2i therapy is poorly understood.

Objectives: The study aimed to assess the initial eGFR dip's impact on prognosis in mentioned populations.

Patients and methods: We systematically reviewed several databases to identify studies analyzing the effect of the initial eGFR dip following the initiation of SGLT-2i on selected outcomes. Randomized controlled trials were included, and a backward snowballing method was applied. The analysis was conducted according to the PRISMA guidelines and registered in PROSPERO (CRD42024527609).

Results: Out of 2.422 papers screened, 14 passed the initial screening, and 5 papers were included in the quantitative analysis. The dip status was reported for all 23890 encompassed patients, with the dip occurring in 13575 of them, representing 56.82% of the analyzed patients (8245(34.51%) in the intervention arm and 5330 (22.31%) in the placebo arm). The initial eGFR dip, regardless of its magnitude, was not linked to an increased risk of adverse kidney outcomes,cardiovascular (CV) composite endpoint, CV mortality (HR 0.85 [95% CI 0.65;1.11], P=0.24) and all-cause mortality (HR 0.90 [95% CI 0.70;1.15], P=0.40).

Conclusions: Unlike in the placebo arms of RCTs, where an eGFR dip was associated with unfavorable outcomes, the early eGFR dip in patients receiving SGLT-2i was either neutral or beneficial. The dip appears to confer a particularly favorable effect in the HFrEF population.