Why wait? Early combination therapy in diabetic kidney disease: lessons from CONFIDENCE
(2026) Metabolism and Target Organ Damage — Vol. 6, n° 3 (2026)
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Ponlot E, Jadoul M Why wait Early combination therapy in diabetic kidney disease lessons from CONFIDENCE.pdf
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- Abstract
- The prevalence of chronic kidney disease (CKD) caused by diabetes mellitus has risen markedly over the past decades, in line with the global increase in type 2 diabetes (T2D). Beyond hyperglycemia, conditions such as obesity, hypertension, atherosclerosis, dyslipidemia, and insulin resistance also contribute to kidney damage, making diabetic kidney disease (DKD) a heterogeneous disorder involving a complex interplay between metabolic dysregulation, hemodynamic changes, and progression of inflammation and fibrosis. Although albuminuria remains a cornerstone for CKD detection, risk stratification, and therapeutic decision-making, a substantial proportion of patients with diabetes and CKD exhibit a non-albuminuric phenotype, highlighting the clinical heterogeneity of DKD beyond traditional albuminuria-based classifications [1]. After decades during which nephroprotection was purely based on renin-Angiotensin system inhibitors (RASi), the emergence of SGLT2 inhibitors (SGLT2i), finerenone (a non-steroidal mineralocorticoid receptor antagonist), and more recently Glucagon-like Peptide-1 (GLP-1) receptor agonists has changed the therapeutic approach to DKD [2]. However, until recently, these drugs were gradually introduced. The COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with CKD and T2D (CONFIDENCE) marks a conceptual shift by proposing an approach based on the early combination of complementary treatments [3]. The CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials have clearly demonstrated that SGLT2i slow the decline in estimated glomerular filtration rate (eGFR), reduce major renal events, and lower the risk of heart failure in DKD (and non-diabetic albuminuric) CKD [4-6]. Beyond randomized clinical trials, accumulating real-world evidence has confirmed the nephroprotective effectiveness of SGLT2i across broader and less selected populations, supporting the generalizability of these findings to routine clinical practice [7] .
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Ponlot, E., & Jadoul, M. (2026). Why wait? Early combination therapy in diabetic kidney disease: lessons from CONFIDENCE. Metabolism and Target Organ Damage, 6(3). https://doi.org/10.20517/mtod.2026.132 (Original work published 2026)