Endocrine Abstracts

Objective

Fat depot in the tongue that represents 25–30% of the total tongue mass is largely unaddressed. It correlates with body mass index. The response to weight reduction induced by different anti-obesity modalities may vary between body fat compartments. Semaglutide, a long acting GLP-1 receptor agonist (GLP-1 RA), has the potential to reduce body mass with at least 2 to 3 times greater weight reduction than other studied GLP-1 RAs. This is the first study that assessed the effect of semaglutide on fat storage in the tongue in obese women with PCOS over 16 weeks.

Research design and methods

We conducted a single-blind, randomized, placebo-controlled prospective study comparing the effects of semaglutide versus placebo. 30 women (aged 33.7 ± 5.3 years, BMI 36.1 ± 3.9 kg/m², mean ± SD) diagnosed with PCOS by Rotterdam criteria, phenotype A, were randomized in a 1:1 ratio to semaglutide 1.0 mg (SEMA) or placebo group. Quantification of the tongue volume, fat and proportion of fat were obtained by MRI analysis. Total tongue volume was inferred via summation of the tongue mask voxels over all slices and multiplied by single voxel volume. Number of voxels defining the fat tissue was extracted with AFNI.

Results

25 patients concluded the study, 5 were excluded due to protocol violation associated with limitations due the COVID-19 pandemic. Weight reduction was significantly greater in SEMA when compared to placebo group (–5.2 ± 4.0 kg vs + 1.9 ± 5.6 kg, P = 0.001). BMI decreased by 1.9 ± 1.5 kg/m² in SEMA and increased by 0.7 ± 1.9 kg/m² in placebo group. The tongue fat reduction and reduction in tongue fat proportion were significantly greater in SEMA than in placebo (–1944 ± 5510 mm³ in SEMA vs + 3116 ± 4868 mm³ in placebo, P = 0.022 and –2% ± 7% in SEMA vs + 4% ± 6% in placebo, P = 0.01, respectively). Change in the total tongue volume did not significantly differ between the two groups. In SEMA, the tongue fat and tongue fat proportion were significantly reduced in 47% of patients whereas in the placebo group the tongue fat was reduced in only 17% of subjects. By correlation analysis we also found that the reduction of the tongue fat was associated with the reduction of body mass.

Conclusion

Compared with placebo, semaglutide treated patients lost significantly more fat in the tongue. Future studies are needed to assess the clinical importance of the observed composition change in this unique therapeutic target, particularly in populations with obesity related sleep apnea, including PCOS.