Case Presentation: A 31-year-old female with a past medical history of obesity, angioedema, and ADHD presented to the ED for progressive bilateral numbness and weakness in both extremities starting after she increased her Semaglutide dosage by an unknown amount 6 days prior . The vital signs demonstrated slight tachycardia, otherwise were unremarkable. On physical exam, she had poor grip strength, 3/5 strength in bilateral upper extremities, 4/5 strength in bilateral lower extremities, 2+ patellar, biceps, Achilles, and brachioradialis reflexes. Pertinent labs when admitted included normal B12, folate and A1C. Urinalysis demonstrated 3+ proteins. MRI brain without IV contrast was unremarkable. She was admitted to the general floor with further workup showing +ANA 1:1280 nuclear homogenous pattern, Sjogren’s AB positive, an elevated C-reactive protein (CRP) of 7.7, and an elevated erythrocyte sedimentation rate (ESR) of 88. Neurology and rheumatology teams were consulted for progressive ascending weakness leading to quadriparesis and areflexia. Patient was started on 5 days of empiric IVIG for concern for GBS, which is first line treatment for non-ambulating adults. Lumbar puncture showed normal cerebrospinal fluid (CSF) analysis, ruling out infectious causes. The patient developed worsening shortness of breath leading to emergent transfer to Neuro ICU and intubation. Rheumatology team started patient on intravenous methylprednisolone for possible drug induced lupus. Patient was found to have +anti-histone antibody, however given proteinuria she was thought to have a more systemic lupus presentation. She then underwent EMG with findings consistent with a demyelinating disorder. The patient was treated for lupus-induced demyelinating GBS and had 7 sessions of plasma exchange (PLEX) therapy. Patient was then started on mycophenolate mofetil, hydroxychloroquine, and prednisone for lupus management and was to follow up with Rheumatology as an outpatient. At the time of discharge to an inpatient rehab unit, she had a tracheostomy tube, PEG tube, and persisting muscle weakness documented.
Discussion: GLP-1 receptor agonists mimic incretin hormones to regulate blood glucose by delaying gastric emptying and stimulating glucose-dependent insulin secretion (1). About one in five US adults with type 2 diabetes are using these medications as they improve diabetes outcomes while reducing inflammatory cytokines (2). With increasing use of GLP-1 agonist medications, the influence of these medications on immunomodulatory pathways has been further studied. A retrospective study in 2025 using a database of adults 18 and up with type 2 diabetes comparing prevalence of autoimmune conditions between GLP-1 agonists and DPP4 inhibitor medications found that use of GLP-1 agonists exhibited increase in multiple autoimmune conditions (3). One of the proposed mechanisms behind GLP-1 agonists and autoimmunity is by increasing the population of double-negative B cells; a type of antibody-generating B cell frequently implicated in autoimmune diseases such as lupus (4,5).
Conclusions: This patient experienced a rare but severe autoimmune reaction to GLP-1 agonist therapy, leading to new-onset lupus and rapid demyelinating Guillain-Barré syndrome. Further research is essential to understand and mitigate these immune-related risks. This case underscores the need for clinician awareness of potential autoimmune complications following GLP-1 agonist therapy.