SAT-527 Addition of Dulaglutide to Immunosuppressive Therapy Markedly Reduces Insulin Requirements in a Patient with Insulin Antibody-Mediated Resistance

Abstract Disclosure: M.M. Fatakdawala: None. R. Gaba: None. C.E. Ramirez Bustamante: None. A. Balasubramanyam: None. N. Ram: None. J. Faruqi: None. Background: Insulin antibody-mediated resistance is an autoimmune condition wherein autoantibodies bind to insulin and reduce its effectiveness, resulting in severe hyperglycemia.1,2 Currently, no standardized treatment exists for insulin antibody-mediated resistance. We describe the course of a patient with insulin antibody-mediated resistance and partial response to immunosuppressive therapy whose insulin requirements decreased substantially following the addition of dulaglutide. Clinical Case: A 59-year-old lean (BMI 23.79 kg/m²) Hispanic woman with longstanding diabetes and rheumatoid arthritis was referred to our endocrine clinic. At first, she responded well to oral glucose-lowering agents. However, 15 years after the initial diagnosis, she presented to the hospital with multiple admissions for diabetic ketoacidosis (DKA), following which she experienced persistent hyperglycemia. Further workup revealed negative autoantibodies (Glutamic Acid Decarboxylase (GAD)-65 antibodies: <5; anti-pancreatic islet cell antibodies (ICA): <1:1), fasting C-peptide 1.02 ng/mL, severe hypertriglyceridemia (>5000 mg/dL), and HbA1c 16.2% (increased from 8.3% a year prior). Her insulin requirements were nearly 300 units daily. She was diagnosed with SLE, Sjogren’s, and rheumatoid arthritis, and placed on prednisone and mycophenolate mofetil. Insulin antibodies were also present at high titers (>625 U/mL). Following initiation of this immunosuppressive regimen, the HbA1c improved to 7.5% within 10 months. Her glycemic control fluctuated during the next 5 years, with HbA1c ranging from 6.2% to 8.1%, and her insulin requirements were consistently ∼300 units daily (3.3 units/kg). We added dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP1-RA). Four months following the addition of dulaglutide, she experienced frequent episodes of symptomatic hypoglycemia, therefore doses of both insulin and dulaglutide were decreased. She lost 6 kg over 7 months, then maintained a stable weight. The most recent HbA1c is 7.7%, without further episodes of hypoglycemia on a regimen of etanercept (50mg q7d), prednisone (5mg qd), mycophenolate mofetil (1500mg bid), metformin (1000mg bid), empagliflozin (25mg qd), dulaglutide (0.75 mg q10d), glargine insulin (62 units/d), and small doses (<3 units) of aspart insulin as needed with meals. Conclusion: Insulin resistance due to the development of anti-insulin autoantibodies is a rare and challenging condition to treat. This patient’s case demonstrates the effectiveness of GLP1-RAs as an adjunctive treatment to decrease insulin resistance and supports a potential immunomodulatory effect of this class of drugs. Further studies should explore the beneficial mechanisms of GLP1-RAs in this autoimmune condition, and its use as a therapeutic option for patients with insulin antibody-mediated resistance. Presentation: Saturday, July 12, 2025