SGLT Inhibitors for Heart and Kidney Disease in Type 1 Diabetes

Developing a path forward for sodium-glucose cotransporter (SGLT) inhibitor treatment for heart and kidney disease in people with type 1 diabetes (T1D) is essential. This article offers the perspective of experts from the fields of endocrinology, nephrology, and cardiology on available data for the efficacy and safety of SGLT inhibitors in T1D, how the far more extensive data from people with type 2 diabetes (T2D) and people without diabetes would be expected to translate to T1D, and what steps are required to advance toward regulatory approvals and clinical uptake of SGLT inhibitors in T1D for heart and kidney disease. Our conclusion is that the mechanisms driving efficacy of SGLT inhibitors for heart and kidney disease in T2D and nondiabetic disease are likely applicable to T1D and that in light of the data supporting efficacy in these populations, registrational trials in T1D might not require powering for traditional event-based outcomes and investigators may instead rely on suitable surrogate end points, allowing for more feasible trials. Investigators in these trials must also carefully collect data associated with diabetic ketoacidosis (DKA), the critical risk of SGLT inhibitor use in T1D. DKA risk mitigation is essential for SGLT inhibitor use in T1D; protocols to mitigate risk have been developed, but rigorous data on their effectiveness are lacking. We describe a roadmap to advance SGLT inhibitors for T1D heart and kidney disease, which includes the use of feasible trial designs based on surrogate end points and rigorous safety protocols to minimize DKA events.