Combining SGLT2i and aldosterone inhibitors significantly increased the rate of a 30% reduction in UACR compared to SGLT2i alone (RR 2.38; 95% CI 1.46-3.46) and MRA alone (RR 1.34; 95% CI 1.12-1.60).
Meta-Analysis
Does the combination of SGLT2i and aldosterone inhibitors improve UACR reduction compared to either monotherapy in patients with chronic kidney disease?
Combining SGLT2i and aldosterone inhibitors significantly improves albuminuria reduction in CKD patients compared to either monotherapy without increasing serious adverse events.
Effect estimate: RR 2.38 (95% CI 1.46-3.46)
p-value: p=<0.001
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and aldosterone inhibitors show promise for treating chronic kidney disease (CKD). This systematic review and meta-analysis explored the efficacy and safety of aldosterone inhibitors plus SGLT2i combination compared to their effects. We searched PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials CENTRAL, and EBSCOhost. We reported dichotomous outcomes as pooled relative ratios and continuous outcomes as standardized mean differences with a 95% confidence interval. Three studies were included in this meta-analysis. The combination therapy was associated with a significantly higher rate of 30% reduction of urine albumin creatinine ratio (UACR) compared to SGLT2i (RR = 2.38, 95% CI, 1.46–3.46, P < 0.001; I 2 = 0%, P = 0.54) and compared to MRA (RR = 1.34, 95% CI, 1.12–1.60, P = 0.001; I 2 = 13%, P = 0.28). It also showed a significant reduction in the UACR compared to SGLT2i (SMD = −1.47, 95% CI, −2.25 to −0.68, P = 0.0003; I 2 = 78%, P = 0.03) but no significant reduction compared to aldosterone inhibitors (SMD = −0.10, 95% CI, −0.38 to 0.19, P = 0.51; I 2 = 67%, P = 0.05). The pooled data showed no significant difference in the incidence of serious adverse events between the combination therapy and SGLT2i (RR = 1.01, 95% CI, 0.72–1.41, P = 0.96; I 2 = 0%, P = 0.58) or MRA (RR = 1.01, 95% CI, 0.79–1.30, P = 0.92; I 2 = 0%, P = 0.90). In conclusion, combining SGLT2i and aldosterone inhibitors may offer a promising approach for managing albuminuria and potentially slowing kidney disease progression in CKD patients. We registered the protocol in PROSPERO CRD42024511675. Los inhibidores del cotransportador de sodio-glucosa tipo 2 (iSGLT2) y los inhibidores de la aldosterona muestran resultados prometedores en el tratamiento de la enfermedad renal crónica (ERC). Esta revisión sistemática y metanálisis exploró la eficacia y la seguridad de la combinación de inhibidores de la aldosterona e iSGLT2 en comparación con sus efectos. Se realizaron búsquedas en PubMed, Scopus, Web of Science, el Registro Cochrane Central de Ensayos Controlados CENTRAL y EBSCOhost. Los resultados dicotómicos se presentaron como razones relativas agrupadas y los resultados continuos como diferencias de medias estandarizadas con un intervalo de confianza del 95%. Se incluyeron tres estudios en este metanálisis. La terapia combinada se asoció con una tasa significativamente mayor de reducción del 30% del cociente albúmina-creatinina en orina (UACR) en comparación con SGLT2i (RR = 2,38, IC del 95%, 1,46: 3,46, P < 0,001; I2 = 0%, P = 0,54) y en comparación con MRA (RR = 1,34, IC del 95%, 1,12: 1,60, P = 0,001; I2 = 13%, P = 0,28). También mostró una reducción significativa en el UACR en comparación con SGLT2i (SMD=-1,47, IC 95%, -2,25: -0,68, P= 0,0003; I2= 78%, P=0,03) pero ninguna reducción significativa en comparación con los inhibidores de la aldosterona (SMD=-0,10, IC 95%, 0,38: 0,19, P= 0,51; I2= 67%, P=0,05). Los datos agrupados no mostraron diferencias significativas en la incidencia de eventos adversos graves entre la terapia combinada y los inhibidores del SGLT2 (RR = 1,01; IC del 95%, 0,72-1,41; p = 0,96; I 2 = 0%, p = 0,58) o la ARM (RR = 1,01; IC del 95%, 0,79-1,30; p = 0,92; I 2 = 0%, p = 0,90). En conclusión, la combinación de inhibidores del SGLT2 e inhibidores de la aldosterona podría ofrecer un enfoque prometedor para el manejo de la albuminuria y, potencialmente, ralentizar la progresión de la enfermedad renal en pacientes con ERC.
Hageen et al. (Wed,) conducted a meta-analysis in chronic kidney disease (CKD). SGLT2i and aldosterone inhibitors combination vs. SGLT2i or MRA alone was evaluated on 30% reduction of urine albumin creatinine ratio (UACR) (RR 2.38, 95% CI 1.46-3.46, p=<0.001). Combining SGLT2i and aldosterone inhibitors significantly increased the rate of a 30% reduction in UACR compared to SGLT2i alone (RR 2.38; 95% CI 1.46-3.46) and MRA alone (RR 1.34; 95% CI 1.12-1.60).