GLP-1 receptor agonists significantly impair taste function.

Over 10% of the US population are prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to combat obesity. Although they decrease cravings for foods, their influence on chemosensory function is unknown. We employed state-of-the-art quantitative taste and smell tests to address this issue. The 53-item Waterless Empirical Taste Test (WETT®) and the 40-item University of Pennsylvania Smell Identification Test (UPSIT®) were completed by 46 persons taking GLP-1 RAs and 46 controls matched on age, sex, smoking behavior, and COVID-19 infection histories. Data were analyzed using analyses of variance. The WETT® scores were significantly diminished in the GLP-1 RA group relative to controls [total means (95% CIs) = 28.61 (25.66,31.56) and 40.63 (38.35,42.91), p < 0.001, η = 0.37]. Eighty five percent of the GLP-1 subjects scored worse than their individually matched controls. All 5 WETT® subtest scores were similarly affected (ps < 0.001). Smell function, although slightly decreased on average, was not significantly impacted (p = 0.076). Women outperformed men on all tests. Remarkably, UPSIT® and WETT® scores were higher, i.e., better, in those reporting nausea, diarrhoea, and other GLP-1-related side effects. This study demonstrates, for the first time, that GLP-1 RAs alter the function of a major sensory system, significantly depressing the perception of all five basic taste qualities. The physiologic basis of this effect is unknown but may involve GLP-1 receptors in the brainstem and afferent taste pathways, as well as vagus nerve-related processes.