Semaglutide and immunosuppression dramatically cut insulin needs in young woman with Type B insulin resistance

Type B insulin resistance (TBIR) is a rare autoimmune disorder characterized by immunoglobulin G (IgG) autoantibodies targeting the insulin receptor. These antibodies act as partial agonists, leading to severe insulin resistance and hyperglycemia at high titers, and hypoglycemia at low titers. TBIR typically affects middle-aged women with other autoimmune diseases, but can present in younger individuals. Early recognition and timely immunosuppressive therapy are critical to prevent metabolic complications and achieve remission, as standard insulin therapy is often insufficient.

This case report details a 20-year-old Hispanic woman presenting with diabetic ketoacidosis (DKA), severe refractory hyperglycemia, and extreme insulin resistance. She required high doses of U-500 insulin, exceeding 4 units/kg/day intravenously. Diagnostic evaluation included biochemical testing and immunologic studies, with insulin receptor antibody testing confirming TBIR. The therapeutic strategy involved high-dose insulin, adjunctive metabolic agents including the GLP-1 receptor agonist semaglutide (low-dose), and subsequent immunosuppressive therapy with rituximab and azathioprine. Continuous glucose monitoring (CGM) was used for dynamic glucose assessment.

Initial management with high-dose insulin was largely ineffective, with the patient requiring over 5,000 units of insulin daily. Introduction of adjunctive therapy with metformin and low-dose semaglutide significantly reduced daily insulin requirements from over 5,000 units to 200 units. This marked improvement highlighted the utility of incretin agonists in managing the severe insulin resistance. Immunologic studies revealed elevated C-peptide and adiponectin, along with positive antinuclear and anti-Smith ribonucleoprotein antibodies, confirming the autoimmune etiology. Subsequent treatment with rituximab and azathioprine led to a complete discontinuation of insulin within one week. However, the patient's course was complicated by a serum sickness-like illness and recurrent fasting hypoglycemia, which necessitated management with glucocorticoids and diazoxide. This demonstrates the complex, biphasic nature of TBIR.

Adjunctive semaglutide and metformin reduced daily insulin requirements from over 5,000 units to 200 units.