Title

Semaglutide and Immune Modulation: A case of Semaglutide-Induced new onset Lupus causing demyelinating Guillain-Barré Syndrome

Authors

Sahar A. Bhai, DO Lucas Hopkins, MD

Introduction

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 use these medications, causing improvement in diabetes and reduction of inflammatory cytokines (2). However, GLP-1 agonists have also been linked to autoimmune activation (3). This case highlights a patient who was found to have a new onset manifestation of lupus after increasing her Semaglutide dose; presenting with a rapid, lupus-induced, demyelinating Guillain-Barré Syndrome (GBS).

Case Presentation

A 31-year-old female with past medical history of obesity, angioedema, and ADHD presented to the ED for progressive bilateral extremity numbness and weakness after she increased her Semaglutide dosage by an unknown dosage 6 days prior. Vital signs demonstrated slight tachycardia with a pulse of 107 BPM, otherwise 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 included normal B12, folate and A1C. Urinalysis demonstrated 3+ proteins. MRI brain without IV contrast was unremarkable. She was admitted to the general floor. Further workup demonstrated +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 causing quadriparesis and areflexia. Patient was started on 5 days of empiric IVIG for possible GBS, which is typical first line treatment for non-ambulating adults. Lumbar puncture showed normal cerebrospinal fluid (CSF) analysis, ruling out infection. The patient developed worsening shortness of breath and was subsequently intubated and transferred to Neuro ICU. Rheumatology team started patient on intravenous methylprednisolone for possible drug-induced lupus. Patient was found to have +anti-histone antibody. She 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 outpatient. At the time of discharge to an inpatient rehab unit, she had a tracheostomy tube, PEG tube, and persisting muscle weakness.

Discussion

GLP-1 agonist medications have emerged as highly effective for weight loss and management of glycemic index. With increasing use of GLP-1 agonists, their role on immunomodulatory pathways has been examined. A retrospective study comparing prevalence of autoimmune conditions between GLP-1 agonists and DPP4 inhibitors found that use of GLP-1 agonists exhibited increase in multiple autoimmune conditions (4). A proposed mechanism behind GLP-1 agonists and autoimmunity is by increasing the population of double-negative B cells; a type of B cell frequently implicated in autoimmune diseases such as lupus (5,6). 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.

References

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