Semaglutide and Taste in Women With Obesity and Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Study.

CONTEXT: Relationship between obesity and the sense of taste is complex, with many inconsistent and conflicting findings that are largely methodology dependent. The impact of glucagon-like peptide-1 analogues on taste remains largely unaddressed. METHODS: In this 16-week, single-blinded, placebo-controlled study, 30 women with polycystic ovary syndrome (PCOS), aged 33.7 ± 6.1 years with a body mass index of 36.4 ± 4.4 kg/m2 were randomized to semaglutide 1.0 mg once weekly or placebo. Change in taste recognition was assessed by 16 strips impregnated with 4 different concentrations of the 4 basic tastes. Tongue biopsies were performed for gene expression analysis. Brain responses to visual cues of sweet and savory foods and to sweet solution dripping on the tongue were evaluated by functional magnetic resonance imaging. RESULTS: Semaglutide improved overall taste recognition score from 11.9 ± 1.9 points to 14.4 ± 1.0 points, with an estimated treatment difference of 2.5 points (95% CI, 1.7-3.3). The genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste signaling transduction pathways, neural plasticity, and renewal of taste buds, showed differential RNA expression by a multi-tiered analytical pipeline. Semaglutide decreased activation of putamen in response to visual food cues and increased activity in the angular gyrus of the parietal cortex in response to sweet solution after meal intake (semaglutide vs placebo, P < .001). CONCLUSION: In women with obesity and PCOS, semaglutide improved an overall taste recognition score, altered RNA expression in the tongue and modified brain activity in response to sweet and savory food cues and to tasting sweet solution.