Mitigating Diabetic Ketoacidosis in People with T1D and Chronic Kidney Disease on an SGLT1&2 Inhibitor: Ketosis Risk Factor Determination and Incorporation into an Enhanced Glucose Ketone Report - Project Summary It is estimated that 1.8 million people in the U.S. have type 1 diabetes (T1D) and of these, at least 20% have chronic kidney disease (CKD). Sodium-glucose cotransporter inhibitors (SGLT2i) and similar medications improve glycemic control and are cardioprotective and kidney protective. However, in trials of SGLT2i as an adjunct to insulin in patients with T1D, potential benefits were not fully realized due to increased incidence of diabetic ketoacidosis (DKA). Future approval of SGLT2i for T1D will depend on a more comprehensive understanding of ketosis risks and feasible strategies for prevention of DKA. Use of continuous ketone monitoring (CKM) may allow for the safe use of SGLT2i in patients with T1D, but patient use of the ketone data in real-time and patient and provider use of a retrospective combined CGM/CKM report will both be critical components of how CKM data may help facilitate the safe use of SGLT2i therapy to improve health outcomes. The HealthPartners International Diabetes Center (IDC) provides comprehensive care for over 7000 patients with T1D in Minnesota and conducts extensive continuous glucose monitoring (CGM), insulin management, and dietary management research in this population. Over the last 40 years, IDC has played a critical role in the evaluation and implementation of new diabetes therapies into practice. We have developed the consensus standard CGM data report (Ambulatory Glucose Profile: AGP) used by all major CGM manufacturers, clinicians, and researchers globally. We have led or contributed as a participating site in clinical trials evaluating the safety and efficacy of most new diabetes medication classes in use, including SGLT2i therapy. The overall goals of this proposal are to develop and evaluate a novel DKA risk mitigation strategy in order to support the safe use of SGLT2i therapy in patients with T1D. We propose studying SGLT2i medications with a focus on patients with T1D and mild to moderate CKD; this group is the most likely to benefit from the SGLT2i kidney protective effects and, once approved for use in T1D, patients at risk for kidney disease may be prioritized for treatment with SGLT2i therapy. The DKA risk mitigation strategy we propose will leverage early detection of risk for DKA through CKM technology and our team's expertise in developing and implementing standardized, comprehensive, and clinically relevant reports for CGM data. The combined CGM/CKM report that we propose, in addition to continuous glucose and ketone data, will incorporate patient data on potentially modifiable ketosis risk factors. The CGM/CKM report will be refined taking into account the preferences of patients and providers, ensuring an accessible and interpretable user interface and supporting sustained behavior changes to prevent episodes of ketosis and to ensure that when episodes of ketosis do occur, they do not progress to DKA. This proposal builds on our extensive clinical and research expertise in diabetes care, qualitative and quantitative analyses, and leadership in optimization of CGM reports to improve glycemic control and long-term clinical outcomes while preventing DKA in patients with T1D and CKD progression.
