The evaluation of two response thresholds to continuous ketone monitoring information minimising ketosis in people with type 1 diabetes treated with sotagliflozin. - type 1 diabetes (T1D) is…

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded the University of Melbourne a Cooperative Agreement totaling $987,196 under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) on September 12, 2025, with a completion date of August 31, 2027. This research initiative will evaluate two response thresholds for continuous ketone monitoring to minimize diabetic ketoacidosis (DKA) risk in individuals with Type 1 Diabetes (T1D) receiving sotagliflozin therapy. The study addresses a critical gap in diabetes management by investigating the most appropriate ketone threshold levels that should trigger patient interventions when using sodium glucose linked transporter inhibitors (SGLTIs)—a class of medications that have demonstrated significant cardiovascular and renal benefits in Type 2 Diabetes but have been restricted in T1D populations due to elevated DKA risk.

The proposed research involves a randomized-controlled trial enrolling 115 participants who will receive dapagliflozin 10 mg/day in conjunction with a continuous glucose and ketone monitor (CGKM) paired with a response algorithm for elevated ketone levels. By identifying optimal ketone response thresholds, this study will generate evidence to support safer integration of SGLT inhibitors into T1D treatment protocols, potentially expanding therapeutic options for a patient population experiencing significantly elevated mortality rates and reduced life expectancy compared to the general population.

The evaluation of two response thresholds to continuous ketone monitoring information minimising ketosis in people with type 1 diabetes treated with sotagliflozin. - type 1 diabetes (T1D) is associated with three times the mortality of the general population and on average an 11-year reduction in life expectancy. Cardiovascular disease (CVD) and renal disease are major contributing factors to increased mortality in people with T1D. Sodium glucose linked transporter inhibitors (sglti) have revolutionized the management of type 2 diabetes as they can improve glucose levels and significantly reduce the development of CVD and renal complications which include a reduction in mortality, however people with T1D are missing out on this revolutionary treatment as they can cause diabetic ketoacidosis. While sglti therapy as an adjunct to insulin may benefit people with T1D, in general their use has been associated with a significantly increased risk of diabetic ketoacidosis (DKA) which may occur in the absence of hyperglycemia. For example, the pooled analysis of depict-1 and depict-2 participants showed that over 52 weeks of treatment, the incidence of adjudicated DKA was numerically higher in people with T1D treated with dapagliflozin 5 MG/day or 10 MG/day than with placebo (4.0% and 3.5% VS. 1.1%). Therefore, regulatory authorities have continued to not approve the use of this class of agent in T1D. The early recognition of ketosis is of critical importance in preempting the development of DKA. A continuous glucose and ketone monitor (cgkm) may increase an individual's awareness of rising ketone levels allowing them to take remedial action. However, the most appropriate ketone thresholds at which responses should be initiated remain unknown. We propose a randomized-controlled study where 115 participants are provided with dapagliflozin 10 MG/day and a cgkm in conjunction with a response algorithm to elevated ketone levels. Following a 2-week run-in they will be randomized 1:1 to either initiate remedial action at ketone levels of: 1) 1.0MMOL/l or 2) 1.5MMOL/l. They will be followed for 12 weeks. The primary outcome will be % time spent with ketone levels ≥3.0MMOL/l with secondary outcomes including % time spent with ketone levels >0.6, >1.0, and >1.5MMOL/l, mean interstitial ketone levels, DKA events (n) and behavioral outcomes with comparisons between the two groups. Data from this program of research will substantially advance knowledge of and guide the practical use of a cgkm in preventing DKA in those with T1D treated with sglti.