Precision T1D Platform - New Therapies for Cardio-Renal Complications

Inclusion Criteria: 1. Diagnosis of T1D, defined as hyperglycemia requiring treatment with insulin within one year from diagnosis or, if the onset was after age 35 years, documentation of the presence of hyperglycemia and one or more of the following: 1. presence of circulating T1D-associated autoantibodies, or 2. history of hospitalization for diabetic ketoacidosis, or 3. documented plasma C-peptide below the limit of detection with standard assay (with concurrent blood glucose \>100 mg/dL) 2. Aged 18-75 years, inclusive 3. T1D duration \>10 years 4. HbA1c: 7-10% 5. Meets one of the following, either 1. UACR \> 30 mg/dl with eGFR ≥ 60mL/min/1.73 m2 and receiving standard of care therapy for early DKD Stage 2, including renin angiotensin system blockade (RASB), unless contraindicated or not tolerated, or 2. Early (Stage B HF) defined as NT-proBNP ≥125 pg/mL 6. Willing and able to adhere to schedule of activities and protocol requirements, including written informed consent Exclusion Criteria: 1. Diagnosis of Type 2 diabetes or monogenic forms of diabetes or diabetes secondary to pancreatic disease 2. Use of any active platform treatment arms outside study assignment within 2 months prior to screening. See Appendix A for active treatment arms 3. Current use of GLP-1 receptor agonists or other non-glucose lowering agent 4. Use of aldosterone inhibitors within 2 months prior to screening 5. Immunosuppressive medications within 3 months prior to screening 6. Systolic BP\>160 or diastolic BP \>95 mmHg at screening 7. History of ≥3 severe hypoglycemic events requiring third-party assistance for correction within 3 months prior to screening 8. Evidence of any episode of DKA or non-ketotic hyperosmolar state within 12 months prior to screening 9. Serum potassium \> 5.0 mmol/L at screening 10. Absolute neutrophil count \< 2.0 × 109 per L at screening 11. Platelet count \< 120 × 109 per L at screening 12. Known active tuberculosis, hepatitis B or C at screening, or history of HIV 13. 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 AST or ALT \>2 times upper limit of normal, and/or total bilirubin \>1.3 times upper limit of normal at screening 14. History of severe acquired immune deficiency syndrome or severely immunocompromised status in the opinion of the study site investigator 15. History of biopsy-proven non-diabetic CKD 16. History of any other cause of HF (viral, congenital, valvular) 17. History of heart or renal transplant or currently on chronic dialysis 18. 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 prior to screening 19. Illicit drug abuse within 6 months prior to screening in the opinion of the study site investigator 20. Current heavy alcohol use (for men, ≥5 drinks on any day or ≥15 drinks per week; for women, ≥4 drinks on any day or ≥8 drinks per week) 21. Participation in another interventional clinical research study within 30 days prior to screening 22. Breastfeeding, pregnancy, or unwillingness to be on contraception during the trial 23. Presence of a clinically significant medical history, physical examination, laboratory finding or other identified study site investigator concern that may interfere with any aspect of study conduct or interpretation of results