Sotagliflozin to Slow Kidney Function Decline in Persons With Type 1 Diabetes and Diabetic Kidney Disease

Study Summary

Powerful new drugs that can prevent or delay end stage kidney disease (ESKD) - so called sodium-glucose cotransporter-2 inhibitors (SGLT2i) - are now available for patients with type 2 diabetes. Whether these drugs have similar effects in patients with type 1 diabetes (T1D) remains unknown because of the few studies in this population, due to concerns about the increase in risk of diabetic ketoacidosis (DKA, a serious, potentially fatal acute complication of diabetes due to the accumulation of substances called ketone bodies) observed with SGLT2i therapy in T1D. One of the few T1D studies conducted to date showed that implementing an enhanced DKA prevention plan can reduce the risk of DKA associated with the SGLT2i sotagliflozin (SOTA) to very low levels. In the present study, a similar DKA prevention program will be used to carry-out a 3-year trial to test the kidney benefit of SOTA in 150 persons with T1D and moderate to advanced DKD. After a 2-month period, during which diabetes care will be standardized and education on monitoring and minimizing DKA implemented, eligible study subjects will be randomly assigned (50/50) to take one tablet of SOTA (200 mg) or a similarly looking inactive tablet (placebo) every day for 3 years followed by 2-months without treatment. Neither the participants nor the study staff will know whether a person was assigned to taking SOTA or the inactive tablet. Kidney function at the end of the study will be compared between the two treatment groups to see whether SOTA prevented kidney function loss in those treated with this drug as compared to those who took the inactive tablet. The DKA prevention program will include participant education, close follow-up with study staff, continuous glucose monitoring, and systematic ketone body self-monitoring with a meter provided by the study. If successful, this study will provide efficacy and safety data that could be used to seek FDA approval of SOTA for the prevention of kidney function decline

Primary Outcome

eGFR at the end of the 8-week drug washout period following the 3-year treatment period, estimated from Central Lab serum creatinine and cystatin C using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and adjusted by its baseline value. Baseline and end-of-washout eGFRs will be considered as the average of two eGFR values taken on two separate days before randomization (V2 and V4) and after the washout (V18 and V19), respectively.

Conditions Studied

Interventions

• DRUG Placebo
• DRUG Sotagliflozin

Study Locations (18)