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

Eligibility Criteria

• * Type1 diabetes (T1D) continuously treated with insulin within one year from diagnosis.
• * Duration of T1D ≥ 8 years;
• * eGFR based on serum creatinine and cystatin C between 20 and 60 ml/min/1.73 m2 at screening;
• * First morning void urinary albumin/creatinine ratio (UACR) ≥200 mg/g at screening;
• * HbA1c \<10% at screening;
• * Receiving standard of care, including renin angiotensin system blockers (RASB) at a clinically appropriate dose, unless contraindicated or not tolerated.
• * Willing and able to comply with schedule of events and protocol requirements, including written informed consent, and willing to wear a continuous glucose monitoring (CGM) device for the entire duration of the study.
• * Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease;
• * Use of non-FDA approved automated insulin delivery devices;
• * Use of any SGLT inhibitor in the previous 2 months;
• * Use of dual medication RASB therapy (spironolactone, eplerenone, finerenone are allowed in combination with RASB therapy);
• * Use of glucagon-like peptide (GLP-1) receptor agonists and other non-insulin glucose lowering agents if in use for less than 3 months and/or not on stable dose at screening;
• * Use of anti tumor necrosis factor (TNF) alpha biologic medications at screening;
• * Known allergies, hypersensitivity, or intolerance to SOTA;
• * History of ≥3 severe hypoglycemic events (requiring third-party assistance for correction) within 3 months of screening;
• * History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar state within 3 months of screening OR \>1 episode of DKA or non-ketotic hyperosmolar state within 12 months of screening;
• * Blood beta-hydroxybutyrate (BHB) \>0.6 mmol/L for \>2 hours on \>2 occasions during the Run-in period;
• * Inadequate beta hydroxybutyrate (BHB) testing (\<50% of the prescribed measurements) during Run-in;
• * History of primary renal glycosuria;
• * History of biopsy-proven non-diabetic chronic kidney disease (CKD);
• * History of kidney transplant or currently on chronic dialysis;
• * Current or past history of decompensated cirrhosis (defined as variceal bleeding, ascites or hepatic encephalopathy), and/or known diagnosis of cirrhosis based on liver biopsy, imaging, or elastography, and/or aspartate aminotransferase (AST) or alanine transaminase (ALT) at screening \>2 times upper limit of normal, and/or total bilirubin at screening \>1.3 times upper limit of normal).
• * History of severe acquired immune deficiency syndrome or human immunodeficiency virus (HIV) infection or severely immunocompromised status;
• * Cancer treatment (excluding non-melanoma skin cancer treated by excision, carcinoma in situ of the cervix or uterus, ductal breast cancer in situ, resected non-metastatic breast or prostate cancer) within one year of screening.
• * Illicit drug abuse within 6 months of screening;
• * Heavy alcohol use (for men, 5 drinks or more on any day or 15 drinks or more per week; for women, 4 drinks or more on any day or 8 drinks or more per week);
• * Participation in another interventional clinical research study within 30 days of screening;
• * Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial;
• * Systolic blood pressure \>155 mmHg or diastolic blood pressure \>95 mmHg at screening;
• * Presence of a clinically significant medical history, physical examination, or laboratory finding that may interfere with any aspect of study conduct or interpretation of results;
• * Any condition that may render the patient unable to comply with study requirements and/or complete the study.