Semaglutide may change perception, brain response to sweet tastes
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Key takeaways:
- Women with obesity reported greater perception of sweet tastes after taking semaglutide for 16 weeks.
- Response to sweet taste in a brain reward center also changed.
BOSTON — In a proof-of-concept study, women with obesity who took semaglutide reported enhanced taste perception, and researchers observed altered gene expression in their tongues and their brain reward response related to sweet tastes.
“Populations that are prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” Mojca Jensterle Sever, PhD, of the department of endocrinology, diabetes and metabolic diseases at the University Medical Centre Ljubljana, Slovenia, said during a press briefing at ENDO 2024. “Obese individuals often perceive tastes as less intense.”
Jensterle Sever and colleagues used taste tests, tongue biopsy analysis and brain imaging to explore effects of semaglutide (Wegovy, Novo Nordisk) on taste perception. The 16-week single-blind, placebo-controlled clinical trial randomly assigned 30 women with obesity and without diabetes (mean age 33.7 years; mean BMI, 36.4 kg/m2), 1:1, to semaglutide 1 mg per week or placebo.
Taste sensitivity was assessed by “chemical gustometry”; 16 taste strips with four different concentrations of sweet, sour, salty and bitter substances were placed on the tongue in random order. Participants were asked to identify the tastes on a points scale. Those in the semaglutide group had significantly enhanced taste perception from baseline — from a mean of 11.9 points to 14.4 points — in contrast to no change for the placebo group. The estimated treatment difference between the groups was 2.5 points (95% CI, 1.7-3.3).
Next, the researchers analyzed gene expression of participants’ tongues. Compared with baseline, they observed changed mRNA expression for the semaglutide group in genes EYA, PRMT8, CRLF1 and CYP1B1, which are associated with taste pathways, neural plasticity, and renewal and differentiation of taste buds.
Finally, the researchers used functional MRI to assess brain reward responses to a sweet solution and to distilled water dripped on the tongue before and after a standardized meal. Compared with the placebo group, the semaglutide group showed significantly increased activity in the angular gyrus of the parietal cortex — a part of the brain with GLP-1 receptors — in response to the sweet solution. This area of the brain is involved in integrating comprehension and reasoning and may play a role in adjusting taste preferences, according to Jensterle Sever.
“The improvement of taste perception and increase in functional activity in the [brain] region [that] integrates multisensory inputs provides ‘food for thought’ on the additional mechanisms by which semaglutide and other incretin-based therapies facilitate changes in food preference and eating behavior that might potentially lead to reductions in body weight beyond appetite suppression,” Jensterle Sever told Healio.
She cautioned that the study findings have limited clinical implications. The role of taste perception in weight loss needs further study.
“Our proof-of-concept study assessed only a specific taste in a study environment, which may not reflect everyday experience. Taste perception can vary significantly from person to person, limiting the generalizability of our results. Additionally, mRNA sequencing has inherent limitations and does not directly represent changes in protein levels or activity,” she said.
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Jensterle Sever M, et al. OR33-02. Presented at: ENDO annual meeting; June 1-4, 2024; Boston.
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