Glucagon-Like Peptide-1 Analog–Type Amyloidosis: A Case Report and Review of the Literature

Amyloidosis is a heterogeneous group of diseases characterized by extracellular deposition of insoluble proteins. Glucagon-like peptide-1 analog (AGLP1)-type amyloidosis is a rare iatrogenic form of amyloidosis localized to areas of glucagon-like peptide-1 analog injections. In this study, we describe a case of AGLP1-type amyloidosis presenting as a subcutaneous mass on the abdomen of a 71-year-old woman with a history of liraglutide, semaglutide, and tirzepatide use. Biopsy, including Congo red stain, was consistent with an amyloid deposit. Amyloid protein identification by liquid chromatography tandem mass spectrometry showed a typical amyloid profile with low spectra for liraglutide. Immunohistochemistry, subsequently performed, showed that the amyloid deposits were positive for glucagon; there is an extensive peptide homology between liraglutide and glucagon. Only 3 cases of AGLP1-type amyloidosis have been previously reported. It is vital for clinicians and pathologists to be aware of AGLP1-type amyloidosis given the increasing worldwide use of GLP-1 agonists, as well as the potential for misdiagnosis of systemic amyloidosis, which has profound therapeutic and prognostic implications.