Trial of Semaglutide for Diabetic Kidney Disease in Type 1 Diabetes

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