6468 Once-Weekly Semaglutide and Taste Perception in Women with Obesity

Abstract Disclosure: M. Jensterle Sever: None. J. Kovac: None. A. Vovk: None. S. Battelino: None. T. Battelino: None. A. Janez: None. Objective: Semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that causes weight loss by reducing appetite and lowering the desire for energy-dense, salty, and spicy foods, thereby reducing energy intake. We hypothesized that semaglutide would improve the taste sensitivity and modulate the tongue transcriptomic profile associated with gustatory coding in women with obesity.Design: We conducted a 16-week, single-blinded, randomized, placebo-controlled clinical trial involving 30 women aged 33.7 ± 6.1 years with a body mass index of 36.4 ± 4.4 kg/m2, randomized in a 1:1 ratio to once-weekly semaglutide 1.0 mg or a placebo (ClinicalTrials.gov number, NCT04263415). Methods: Taste sensitivity was assessed by strips impregnated with different concentrations of four basic tastes. Biopsies of the tongue were performed for the gene expression analysis. The brain responses were evaluated by functional MRI with the sweet solution dripping onto the tongue before and after a standardized meal intake. Results: Semaglutide improved the taste sensitivity expressed as a mean (± SD) from 11.9 ± 1.9 points to 14.4 ± 1.0 points, with an estimated treatment difference (ETD) of 2.5 points [95% CI, 1.7 to 3.3]. Genes EYA, PRMT8, CRLF1, and CYP1B1, associated with taste signaling transduction pathways, neural plasticity, and renewal of taste buds in the tongue, exhibited differential RNA expression across all tests performed by a multi-tiered analytical pipeline. Semaglutide increased functional activity in the angular gyrus of the parietal cortex in response to tasting the sweet solution compared to the distilled water 30 minutes after a standardized meal intake (semaglutide vs. placebo, p<0.001). Angular gyrus functions as a cross-modal hub where converging multisensory information is combined and integrated to comprehend and give sense to events and stimuli, manipulate mental representations, and solve familiar problems. It expresses GLP-1 receptor and is a part of the default mode network associated with shifting attention between rewarding and neutral stimuli, which has reduced connectivity in people with obesity. Conclusion: The present study provided evidence that semaglutide improved taste sensitivity, altered gene expression in the tongue linked to taste perception, and altered functional brain activity in an integrative hub beyond hypothalamic and midbrain reward circuitry in response to the sweet taste stimulus. Future studies will clarify whether the efficacy of semaglutide in treating obesity is also a »matter of taste«. Presentation: 6/1/2024