From Evidence to Action: Advancing Timely Implementation of Triple Therapy in Type 2 Diabetes Mellitus and CKD

Abstract

Amid rapid advances in treating chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) and evolving guidelines, implementation remains a major bottleneck. Suboptimal implementation of guidelines, from lack of albuminuria testing for early CKD detection to delayed initiation of triple therapy with renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and nonsteroidal mineralocorticoid receptor antagonists (nsMRA), may deny patients kidney and cardiovascular benefits. We emphasize the residual risk despite RASi-SGLT2i therapy and the added value of nsMRA, and address real-world implementation challenges. The addition of a nsMRA may delay the need for kidney replacement therapy (KRT) by up to a decade. Based on epidemiological data, > 90% of patients eligible for therapy may be diagnosed and managed in the primary care setting, identifying the owners of the process, in close collaboration with nephrology, endocrinology, cardiology, and internal medicine, as needed. In addition, primary care provides the optimal setting, given the easy and repeated contact, for ensuring lifestyle measures essential to nephroprotection, as well as maximizing the use of RASi and SGLT2 inhibitors when not contraindicated, together with the rapid initiation of triple therapy, facilitated by its safety profile. In this regard, the CONFIDENCE trial supports the safety and efficacy (in terms of albuminuria reduction) of prescribing simultaneously, nsMRA plus SGLT2i combination therapy on a prior RASi background. In conclusion, widespread uptake of albuminuria assessment in primary care will prevent patients with CKD and T2DM from missing out on the diagnosis or the rapid implementation of optimal guideline-directed therapy.