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JDRF is committed to improving outcomes in people with type 1 diabetes (T1D) through the use of adjunctive drugs that complement insulin therapy. Drugs in the sodium-glucose linked transporter inhibitor class, i.e. SGLT2 and SGLT1/2 inhibitors, have demonstrated efficacy in T1D. However, clinical trials have shown an increased risk of diabetic ketoacidosis (DKA) in people with T1D taking these drugs at the most efficacious doses. We invite applications for research projects that will increase safe and effective use of SGLT inhibitors for T1D.
SGLT2 inhibitors, which block SGLT2-mediated glucose reabsorption in the kidney, lower blood glucose by inducing beneficial glycosuria; the SGLT1/2 inhibitor also transiently blocks SGLT1 activity in the intestine, slowing the rate of glucose absorption into the bloodstream as well. SGLT inhibitors lower HbA1c, increase time-in-target glucose ranges, and reduce postprandial glucose excursions and glycemic variability in people with T1D. SGLT inhibitors have also demonstrated non-glycemic metabolic benefits in the form of beneficial weight loss and blood pressure reduction. Emerging evidence indicates that SGLT2 inhibitors also offer renal and cardiac protection in type 2 diabetes, long-term benefits that may be expected a priori to translate to T1D but have yet to be tested in that population.
The largest hurdle to safe, effective use of SGLT inhibitors in T1D is the risk of DKA. People with T1D are at heightened risk for DKA relative to people with T2D or the nondiabetic population, and numerous clinical trials have shown increased rates of DKA, including euglycemic DKA, in people with T1D taking SGLT inhibitors compared to placebo. While several SGLT inhibitors are approved for T1D in Europe and Japan as insulin adjuncts, none are yet approved for T1D in the United States. JDRF recognizes the potential benefits of SGLT inhibitors for T1D and the urgent need to mitigate their associated risk of DKA to support the successful use of these effective therapies in T1D worldwide.