Cystic Fibrosis and Hemochromatosis Carriers May Be Prone to Glucagon-like Peptide-1 Agonist Pancreatitis: 3 Cases

Abstract

Glucagon-like peptide-1 (GLP-1) agonists are widely used in the management of type 2 diabetes and obesity, with their therapeutic scope expanding to address cardiometabolic and cardiorenal conditions. However, their increasing use has been associated with potential adverse effects, including acute pancreatitis (AP). The exact prevalence of GLP-1 agonist-induced AP remains uncertain and reliable predictors for its onset have yet to be identified. We present 3 cases of class-associated predilection for GLP-1 analog-associated AP in patients with carrier states for hemochromatosis (HC) and cystic fibrosis. Case 1 is a heterozygous carrier for the C282Y HC pathogenic variant. Case 2 is a heterozygous carrier of the Delta F508 deletion of the cystic fibrosis transmembrane regulator (CFTR) gene. Case 3 is compound heterozygous carrier of a single CFTR intron 9 poly T allele pathogenic variant (5T/7T/8T), as well as a single pathogenic variant of the C282Y HC gene. Our observation suggests that carrier states for cystic fibrosis and HC may predispose individuals to GLP-1 agonist-associated AP. Genetic testing for these carrier states should be considered among patients with GLP-1 agonist-associated AP to provide more support and data for this as a potential true risk factor.

Keywords: GLP-1 agonists; acute pancreatitis; chronic pancreatitis; cystic fibrosis; hemochromatosis; heterozygous carrier.