Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes (RT1D)

Inclusion Criteria: Adults (≥18 years) with type 1 diabetes Diabetes duration of ≥5 years Persistent urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g, on the most recent two measurements within the prior 3 years Estimated glomerular filtration rate ≥ 45 mL/min/1.73m2 Stable doses of drugs altering blood pressure (e.g., Angiotensin-converting enzyme inhibitor) required for at least 4 weeks prior to randomization, and requested for the duration of the trial Stable doses of lipid-lowering medications required for at least 4 weeks prior to randomization, and requested for the duration of the trial Adequate contraceptive method for females of child-bearing potential Exclusion Criteria: HbA1c >9%, recent diabetic ketoacidosis, hyperosmolar hyperglycemic state or severe illness requiring hospitalization in past 30 days Other causes of diabetes mellitus, including type 2 diabetes and maturity-onset diabetes of the young (MODY) Chronic kidney disease unrelated to diabetes Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2) or thyroid nodule palpated by endocrinologist at screening Personal history of pancreatitis Current/planned pregnancy or nursing Uncontrolled thyroid disease or hypertension (Systolic blood pressure [SBP] ≥ 160 mm Hg or diastolic blood pressure [DBP] ≥ 100 mm Hg despite treatment) Proliferative retinopathy with treatment in the past 6 months Uncontrolled or potentially unstable diabetic retinopathy or maculopathy, verified by fundus examination with pupil dilation unless performed using a digital fundus photography camera specified for non-dilated examination More than 2 severe hypoglycemic episodes (requiring glucagon and/or assistance from another person) in the past 6 months Frequent hypoglycemia during the last two weeks of the study run-in phase (time below range [<70 mg/dL] ≥4%) Pramlintide and the use of glycemia treatments not approved for type 1 diabetes by the FDA, e.g., metformin, SGT-2 inhibitor, GLP-1 receptor agonist, closed loop insulin delivery using unapproved algorithms Significant systemic conditions or treatment such as cancer or immunomodulators Known liver disease other than non-alcoholic fatty liver disease (NAFLD) or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 IU/L, history of severe gastrointestinal disease (e.g., gastroparesis) or gallstones Body mass index <20 kg/m2 Inability to cooperate with or clinical contraindication for magnetic resonance imaging including severe claustrophobia, nonremovable devices, implanted metal Known or suspected allergy/sensitivity to semaglutide or its excipients Pregnant, breast feeding, or the intention of becoming pregnant The receipt of any investigational drug within 3 months prior to this trial Previously randomized in this trial