GLP-1 Receptor Agonists and Gout: A Narrative Review

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide receptor agonists (GIP RAs) are incretin mimetics that have increased in use in the management of type 2 diabetes and obesity. Understanding the potential impact of incretin mimetics on gout is important because of their increased use and the relationship between obesity, insulin resistance, hyperuricemia, and gout. Current evidence supports that both metabolic and inflammatory pathways overlap between incretin mimetics and gout. Some data suggest a biphasic effect of GLP-1 RAs on gout risk—initially increasing gout flare risk and eventually decreasing flare risk, but this needs confirmation in larger prospective studies. The rapid weight loss that is seen on incretin mimetics may alter the renal handling of uric acid due to the presence of ketone bodies. However, sustained weight reduction and the direct inhibition of NF-κB signaling, reduced NLRP3 inflammasome activation, and alterations in macrophage polarization may reduce gout-related inflammation over the longer term. This narrative review aims to summarize the current understanding of the pharmacologic, metabolic, and immunologic mechanisms linking incretin mimetics with gout and aims to explore the potential implications for clinical management of gout.