Abstract
AbstractBackgroundCurrent guidelines recommend sodium-glucose cotransporter-2 inhibitors (SGLT2i) for kidney protection to a broad range of people with type 2 diabetes (T2D), but many were not represented in key kidney outcome trials and have unclear benefit. We aimed to identify which of these people are likely to benefit.MethodsWe studied 134,420 adults with T2D, estimated glomerular filtration rate (eGFR) ≥20mL/min/1.73m2, no cardiovascular disease or heart failure, starting SGLT2i (34%) or dipeptidyl peptidase-4 inhibitors/sulfonylureas (DPP4i/SU, 66%) in UK primary care (Clinical Practice Research Datalink, 2013-2020). We first validated the hazard ratio (HR) for kidney disease progression (≥50% eGFR decline, end-stage kidney disease, or kidney-related death) from SGLT2i trial meta-analysis. We then integrated this with established prediction models (CKD Prognosis Consortium risk score for 3-year risk of kidney disease progression) to estimate SGLT2i benefit (absolute risk reductions [ARR]) and validated the accuracy of these estimates.FindingsThe multivariable-adjusted SGLT2i HR for kidney disease progression was 0.60 (95%CI 0.52-0.70) compared to DPP4i/SU, consistent with SGLT2i trial meta-analysis and across eGFR/albuminuria subgroups (interaction p=0.36). Predicted SGLT2i benefit was consistent with observed and was substantial (ARR ≥0.85%) in two subgroups: 1) eGFR <60mL/min/1.73m2or albuminuria ≥30mg/mmol; 2) eGFR ≥60mL/min/1.73m2, albuminuria 3-30mg/mmol, and predicted ARR ≥80thpercentile. Benefit was limited (ARR ≤0.38%) in all others with eGFR ≥60mL/min/1.73m2. This latter group with limited benefit comprises 46% of those recommended SGLT2i for kidney protection.InterpretationSGLT2-inhibitor treatment could be targeted to those with substantial predicted kidney protection benefit. Guidelines should consider stratifying treatment recommendations based on predicted benefit.
Publisher
Cold Spring Harbor Laboratory