Sacubitril Valsartan and Prevention of Initial Dip Induced by SGLT2 Inhibitors

Background: Sacubitril valsartan (ARNI) is an export arteriolar dilator as well as an import arteriolar dilator and has been established as a key drug for HFrEF, but its use in CKD has not been established. SGLT2 inhibitors are essential in the treatment of CKD because of their renoprotective effect by correcting intraglomerular pressure through tubuloglomerular feedback. Controlling the initial dip may lead to continuation of the medication and renoprotective effect. In this study, we investigated the possibility of controlling the initial dip by the imported arteriolar dilating effect of ARNI. Methods: 148 patients (group 1) were prescribed SGLT2 inhibitors (dapagliflozin and empagliflozin) in 2022-2024. eGFR decline of ≥5% at visit within 3 months after SGLT2 inhibitor prescription was defined as initial dip and its occurrence was defined as outcome. The relationship between ARNI at the time of SGLT2 prescription and the presence of initial dip was examined by logistic regression analysis using age, male, BMI, systolic blood pressure, DM, hemoglobin, BUN, eGFR baseline, and urinary protein as adjustment factors. In addition, we also analyzed eGFR decline 1 year after initiation of SGLT2 inhibitors using a mixed regression model (group2, n=97). Results: Taking ARNI was associated with the occurrence of initial dip [OR=0.24 (95%CI, 0.06-0.95, p=0.04)]. The analysis of eGFR decline at 1 year after initiation of SGLT2 inhibitors showed that the presence or absence of ARNI was not associated with eGFR decline. In group2, eGFR decline at 1 year was analyzed using a mixed model, and no association was found between ARNI use and eGFR decline (p=0.73). Conclusion: Taking oral ARNI may suppress the initial dip caused by SGLT2 inhibitors. No effect of oral ARNI on eGFR decline was suggested, but long-term follow-up is needed to confirm this.