Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes

Eligibility 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
• * 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