WCN26-2876 Effects of Non-steroidal Mineralocorticoid Receptor Blocker Esaxerenone on Glomerular Hemodynamics in type 2 Diabetic Kidney Disease

contributing to underuse of guideline directed medical therapies. We assessed whether the efficacy and safety of canagliflozin is modified by polypharmacy status in patients with type 2 diabetes and CKD. Methods: We conducted a post-hoc analysis of the CREDENCE trial, which evaluated the effects of canagliflozin on clinical outcomes in participants with type 2 diabetes and albuminuric CKD. Participants were categorized according to polypharmacy status at baseline: no polypharmacy (0-4 medicines), polypharmacy (5-9 medicines), and hyperpolypharmacy (10 medicines). We assessed the relative effects of canagliflozin on kidney, cardiovascular and safety outcomes by baseline polypharmacy status using Cox proportional hazards models. We assessed absolute benefits and harms, expressed as the number of events averted or caused per 1000 patient-years using Poisson regression. The primary outcome was a composite of doubling of serum creatinine, kidney failure or death due to cardiovascular or kidney disease. Results: Among 4401 participants, 612 (14%), 2404 (55%), and 1385 (31%) were categorized as no polypharmacy, polypharmacy and hyperpolypharmacy, respectively. The mean number of medications at baseline was 8. 3 (95% CI 8. 2-8. 4). Those with polypharmacy and hyperpolypharmacy were more likely to be older, male, and to have atherosclerotic cardiovascular disease and a longer duration of diabetes, higher body mass index, systolic blood pressure, and lower eGFR. The effect of canagliflozin on all kidney and cardiovascular outcomes was consistent irrespective of polypharmacy status (all p-interaction >0. 05; Figure 1), with no interaction observed for safety outcomes (all p-interaction >0. 05). While rates of treatment discontinuation were higher with increasing medication burden, treatment discontinuation was consistently lower with canagliflozin versus placebo, regardless of polypharmacy status (HR 0. 80, 95% CI 0. 71-0. 89, p-interaction 0. 16). Because the overall incidence of all-cause hospitalization increased with higher medication burden, absolute risk reductions with canagliflozin treatment were considerably higher in patients experiencing polypharmacy and hyperpolypharmacy (Figure 2). Regardless of polypharmacy status, absolute benefits substantially outweigh any harms defined by DKA, amputation, or volume depletion (Figure 2). Conclusion: In patients with type 2 diabetes and CKD, the net absolute benefits of canagliflozin exceed the serious harms analyzed, irrespective of polypharmacy status. Larger absolute reductions in all-cause hospitalization were observed in those experiencing polypharmacy or hyperpolypharmacy. Polypharmacy should not dissuade clinicians from using an SGLT2 inhibitor in patients with CKD for whom treatment is indicated. I have no potential conflict of interest to disclose. I did not use generative AI and AI-assisted technologies in the writing process.