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BOSTON -- Once-weekly semaglutide (Ozempic, Wegovy) improved taste sensitivity, changed gene expression in the tongue linked to taste perception, and changed brain activity in response to sweet tastes in women with obesity, a researcher reported here.

Sensitivity of four basic tastes -- sweet, sour, salty, and bitter -- increased from 11.9 to 14.4 points for women taking semaglutide whereas placebo remained stable, according to Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, at ENDO 2024, the annual meeting of The Endocrine Society.

"It means that [semaglutide] lowered the detection threshold for certain tastes," she said.

To measure, 16 taste strips impregnated with varying concentrations of the four tastes were placed on each participant's tongue in a pseudo-randomized manner. Then the participant was asked to identify the taste of each strip.

In addition, after RNA sequencing of tongue tissue, four genes -- EYA, PRMT8, CRLF1, and CYP1B1 -- showed differential mRNA expression from baseline in women on semaglutide. "These genes are associated with taste transduction, taste bud development, renewal, and differentiation," Jensterle Sever pointed out.

In another test, functional MRI was used to measure brain activity after a sweet solution was dripped onto the tongue 30 minutes after a standardized meal intake. This test found women on semaglutide had significant increases in functional activity in the angular gyrus of the parietal cortex in response to tasting sweet compared with distilled water.

The angular gyrus is an area of the parietal cortex involved in comprehension and reasoning, "including reorienting the attentional system and giving meaning to external stimuli based on stored memories and prior experiences," explained Jensterle Sever.

Participants also performed a visual cue task during functional MRI scans. After being shown a series of calorie-dense, calorie-low, and non-food cues before and after a meal, women on semaglutide had decreased activation in the putamen in response to calorie-dense foods. Jensterle Sever noted this is an area involved in the reward system, implying less satisfaction from high-caloric food cues in the semaglutide group.

The small trial recruited 30 women with obesity to once-weekly 1-mg semaglutide or placebo. At baseline, the average age was 34, BMI was 36.4, and body weight was 100 kg. All women also had a pre-existing diagnosis of polycystic ovary syndrome (PCOS). Some of the exclusion criteria included diabetes, history of pancreatitis, history of gallbladder disease, smoking, surgical obesity treatment, or pregnancy.

A total of 20% of the cohort had thyroid disease at baseline, 13% each had dyslipidemia and depression, and 10% each had migraines and osteoarthritis.

The 15 women randomized to semaglutide underwent a dose escalation period during the initial 4 weeks of the trial and then remained on a stable dose for the remaining 12 weeks. At the end of the 16 weeks, treatment was discontinued.

Semaglutide was first approved in December 2017 for type 2 diabetes under the brand Ozempic and is available in 0.5-, 1-, and 2-mg doses. Wegovy was later approved in June 2021 for chronic weight management in adults with obesity (BMI of 30 or greater) or for adults with overweight (BMI of 27 or greater) with at least one weight-related condition at a higher dose of 2.4 mg. Of note, this trial used a lower dose of semaglutide (1 mg) than is indicated for weight management.

Adverse events were generally in line with what was seen in the STEP clinical program, which the Wegovy approval was based upon. There was a high frequency of gastrointestinal side effects but 86% were graded as mild or moderate and mostly occurred during the dose titration phase. There were no reports of pancreatitis or gallbladder disease.

"Future studies will clarify whether the efficacy of semaglutide in treating obesity is also a matter of taste," said Jensterle Sever.

She added that this was only a proof-of-concept study testing specific tastes in a study environment and may not reflect typical everyday experience. Taste perception can also vary greatly from person to person due to factors like genetics. The homogenous cohort of women with PCOS may also limit the findings.

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