Utilizing continuous ketone monitors to enable safe use of sglt inhibitors in patients with type 1 diabetes

The University of California, San Diego received a $2.26 million Cooperative Agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847), awarded September 11, 2025, with completion targeted for August 31, 2028. The award funds a two-arm, cross-over clinical trial designed to investigate the safe use of SGLT (sodium-glucose cotransporter) inhibitors in Type 1 Diabetes (T1D) patients through continuous ketone monitoring technology. The research addresses three critical clinical gaps: understanding diabetic ketoacidosis (DKA) risk differences between insulin pump users and multiple daily injection users; evaluating whether continuous ketone monitors enable safe use of higher-dose SGLT inhibitor therapy; and identifying clinical predictors to support appropriate patient selection for SGLT inhibitor treatment.

The study involves 52 total participants—26 using multiple daily insulin injections (MDI) and 26 using hybrid closed-loop insulin pumps—who will receive sotagliflozin (an SGLT inhibitor) at both 200 milligrams and 400 milligrams in random order over six-week treatment periods. Continuous ketone monitoring will be employed during a two-week baseline period and throughout the study duration. This clinical investigation directly supports NIDDK's programmatic objective to promote extramural biomedical research that improves understanding of disease mechanisms and leads to improved prevention, diagnosis, and treatment of diabetes and its complications.

Abstract

Sodium-glucose cotransporter inhibitors (sgltis) improve glycemia in type 1 diabetes (T1D) and provide important cardiorenal benefits. However, their use in T1D is restricted due to an increased risk of diabetic ketoacidosis (DKA). As a result, patients with T1D are left unable to realize the numerous benefits that this class of medication offers. Fortunately, continuous ketone monitors (ckms) have been developed to provide real-time ketone data to patients and, for the first time, the potential for safe use of sgltis. Through extensive research in patients with T1D using sglti, three critical gaps have been identified that require attention. First, individuals using insulin pumps face the highest risk of DKA, which is particularly concerning as the majority of patients in the US currently use pump therapy. Therefore, IT is crucial to understand the differences in DKA risk between insulin pumps and multiple daily insulin injections, and to find ways to reduce this added risk. Second, while higher doses of sglti therapy offer additional clinical benefits such as improved glucose control and weight reduction, they also pose a higher risk of DKA. Thus, evaluating whether CKM devices can enable the safe use of all clinically viable doses is necessary. Third, healthcare practitioners need clinical predictors of ketosis risk to aid in selecting appropriate patients for sglti therapy. This proposal aims to address all three of these identified gaps. To achieve the study objectives, a two-arm, cross-over clinical trial is proposed involving participants using MDI (n=26) and hybrid closed loop insulin pumps (HCL; n=26). Participants will receive the sglti sotagliflozin at both 200 MG and 400 MG in random order for 6 weeks, with CKM used during a 2-week baseline and throughout the study. HCL participants will undergo an additional 6-week treatment period during which a daily basal injection will supplement their HCL therapy. Half of their basal requirement will be provided by the injection and half will be provided by the pump. This approach aims to safeguard pump users from developing ketosis in case insulin delivery from their pump is interrupted. At baseline and after 2 weeks of each treatment, a comprehensive clinical profile-including patient demographics, lab analysis, and CKM data-will be completed to identify predictors of ketosis. The rationale for this work is that CKM can be leveraged to define and mitigate ketosis risk in individuals with T1D receiving sglti therapy. The specific aims are designed to assess risk of different modes of insulin administration (aim 1A), if pump risk can be mitigated with the addition of basal insulin (aim 1B), risk associated with dose of sglti (aim 2) and using clinical data to identify key predictors of ketosis risk (aim 3). Impact: this work will have a rapidly translatable impact on enabling T1D patients to benefit from this vital medication class.