Framework proposes risk-based combination therapy with SGLT2 inhibitors, MRAs, and GLP-1 receptor agonists for CKD.

Chronic kidney disease (CKD) affects over 800 million people globally, posing a significant burden due to progressive kidney damage and heightened cardiovascular disease risk. Despite advancements, residual kidney and cardiovascular risks remain high, necessitating more effective therapeutic strategies. Current standard-of-care often falls short in fully mitigating these risks, highlighting a critical gap for improved patient outcomes. The emergence of agents like SGLT2 inhibitors, non-steroidal MRAs, and GLP-1 receptor agonists offers new avenues for independent and additive benefits, prompting the need for a structured approach to their combined use.

This paper synthesizes evidence from large, randomized trials and meta-analyses to develop a risk-based framework for implementing combination therapy in chronic kidney disease (CKD). The authors analyzed existing data on sodium-glucose co-transporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs), and glucagon-like peptide-1 (GLP-1) receptor agonists to identify their independent and additive benefits. They then proposed a structured approach, anchored in albuminuria and supported by validated risk equations, to guide treatment intensity and timing for multidrug regimens, aiming to optimize patient outcomes and health system efficiency.

The framework emphasizes that SGLT2 inhibitors, non-steroidal MRAs, and GLP-1 receptor agonists offer independent and additive benefits in reducing residual kidney and cardiovascular risk in CKD. Emerging data also suggest that select combinations of these agents may improve safety profiles. > A risk-based approach, primarily anchored in albuminuria levels and supported by validated risk equations, can effectively guide the intensity of treatment and facilitate more timely initiation of multidrug regimens. This strategy is designed to improve health system efficiency by optimizing resource allocation and patient management. The authors highlight that translating these therapeutic advances into improved long-term outcomes for people with CKD will require addressing implementation barriers, developing single-pill combinations, and leveraging adaptive and combination therapy trials. The independent benefits of these drug classes, when combined, offer a powerful strategy to address the multifaceted risks associated with CKD.