[Effect of semaglutide treatment on the body weight and the glucose, insulin and thyroid hormone levels in aging rats with diet-induced obesity.]

Obesity, type 2 diabetes mellitus and associated thyroid diseases are most common among elderly patients. Glucagon-like peptide-1 receptor (GLP-1-R) agonists, including semaglutide, are a promising approach for their treatment, but their effects on metabolic and hormonal parameters, including the thyroid-stimulating hormone (TSH) and thyroid hormone levels, during aging have not been studied. The aim of the work was to study the effect of semaglutide on the body and adipose tissue weight, glucose homeostasis, insulin levels and hormonal status of the thyroid system in aging rats with high-fat diet-induced obesity in comparison with age-matched control animals. Treatment of aged obese rats (18 months) with semaglutide (60 μg/kg/day, 4 weeks) resulted in a decrease in body weight and adipose tissue by an average of 10,5 and 34,9% compared to the untreated group (OB), improved glucose tolerance and insulin sensitivity, as indicated by a decrease in glucose levels 120 min after a glucose load in the OB+Sem group compared to OB group (6,400,53 vs. 8,120,56 mM, p<0,05) and in the insulin resistance index, which did not differ from the control group (C). Semaglutide restored the level of free triiodothyronine reduced in obesity (3±0,16 pM in OB+Sem vs. 2,11±0,09 pM in OB, p<0,05) and normalized the integral thyroid index (fT3+fT4/TSH), demonstrating the restoration of thyrocyte sensitivity to TSH. It also increased the peripheral conversion index (fT3/fT4), as an indicator of the conversion of thyroxine to triiodothyronine (0,125±0,006 rel. units in OB+Sem vs. 0,099±0,002 rel. units in OB, p<0,05). Semaglutide had no significant effect on the thyroid status in aging non-obese rats (C+Sem), except for an increase in the peripheral conversion index compared to the control (0,133±0,004 vs. 0,114±0,005 rel. units, p<0,05). This indicates the prospects for the use of semaglutide for the correction of hypothyroidism in elderly patients with obesity caused by an unbalanced diet.