Effect of Four-Week Semaglutide Therapy and Its Combination with Intranasal Insulin on Thyroid and Gonadal Status in Male Rats with Type 2 Diabetes

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely used now for the treatment of type 2 diabetes (T2D) and obesity. However, its effects on endocrine functions compromised in these conditions remain poorly understood. Moreover, there are no data on the potential enhancement of Semaglutide effects in the presence of intranasal insulin (INI). This study was aimed to investigate the influence of a four-week treatment of mature male rats with T2D using Semaglutide (50 µg/kg/day, s.c.) and its combination with INI (2 IU/rat/day) on hormonal parameters of the thyroid and gonadal systems. T2D was induced by a high-fat diet and a low-dose streptozotocin. Along with glucose homeostasis parameters and insulin levels, the blood levels of thyroid hormones (fT4, tT4, fT3, tT3), thyroid-stimulating hormone (TSH), testosterone, and luteinizing hormone (LH) were assessed. In T2D rats, Semaglutide reduced body weight and fat mass, improved glucose tolerance and insulin sensitivity, restored triiodothyronine levels and peripheral conversion of thyroid hormones. Semaglutide and INI co-application enhanced the stimulatory effects of the former on thyroid hormone levels reduced in T2D, and normalized TSH levels (elevated in T2M) and thyroid gland sensitivity to TSH, as assessed by the integral thyroid index. Both Semaglutide monotherapy and its combination with INI partially restored testosterone levels reduced in T2D, preventing androgen deficiency. Thus, Semaglutide and its combination with INI can be used to correct endocrine disorders in T2D, which is important for clinical endocrinology and reproductive medicine.