WCN26-4303 Effect of finerenone and an SGLT2 inhibitor on the urine proteome: A CONFIDENCE analysis

Introduction: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), confers kidney protection in people with type 2 diabetes (T2D) and chronic kidney disease (CKD) by improving kidney hemodynamics and stabilizing fibrosis.Sodium-glucose cotransporter-2 inhibitors (SGLT2is) represent a distinct drug class with established nephroprotective effects, mediated by hemodynamic mechanisms including reductions in glomerular hyperfiltration.Although both drug classes lower blood glucose levels, emerging evidence suggests that their kidney-protective mechanisms are largely independent and potentially additive.We hypothesized that semaglutide exerts kidney hemodynamic effects irrespective of background SGLT2i therapy.Therefore, we evaluated some kidney-protective effects of semaglutide 1.0 mg stratified by SGLT2i use. Methods:The study is a post-hoc analysis of the REMODEL trial (NCT04865770).Adults with T2D, estimated glomerular filtration rate (eGFR) of 30-75 mL/min/1.73m2, and urine albumin-creatinine ratio (UACR) 20-<5000 mg/g were randomized 2:1 to once-weekly semaglutide subcutaneous 1.0 mg (n=71) or placebo (n=35) for 52 weeks and stratified by concomitant treatment with SGLT2i.Kidney oxygenation (R2*) was assessed by blood oxygenation level dependent magnetic resonance imaging (BOLD-MRI), while mean global kidney perfusion (GKP), renal artery resistive index (RARI), and cortical and medullary estimates of fibrosis (diffusion weighted imaging for the apparent diffusion coefficient ADC) were assessed by phase-contrast MRI measured arterial flow.Results: At baseline, SGLT2i users and non-users exhibited similar eGFR-creatinine, though UACR was higher among SGLT2i users (Table 1).The effect of semaglutide to reduce RARI was observed in both SGLT2i users and non-users (p-interaction p-int=0.29).SGLT2i use did not impact the increase in cortical ADC or delta ADC observed with semaglutide vs placebo, reflecting stabilized fibrosis or lack of progression in both groups (p-int=0.73and p-int=0.53,respectively).The ratio of cortical R2* and medullary R2* from baseline to week 52 in semaglutide and placebo groups did not differ significantly between SGLT2i users vs non-users (p-int=0.88and p-int=0.84,respectively).There was a trend toward a higher GKP in the semaglutide group vs placebo, with similar effects in SGLT2i users and non-SGLT2i users (p-int=0.42). Conclusion:In REMODEL, semaglutide had similar effects to reduce RARI and mitigate fibrosis irrespective of background SGLT2i therapy.The combination of semaglutide treatment with SGLT2i use may confer additional kidney benefits.I have potential conflict of interest to disclose.I am a salaried Novo Nordisk employee I did not use generative AI and AI-assisted technologies in the writing process.