Effect of Submaximal Doses of Semaglutide in Patients with Obesity on Metabolic Profile and Serum Levels of Adipocytokines.

Background: Obesity is closely linked to metabolic dysfunction and systemic low-grade inflammation. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are increasingly utilized for obesity treatment due to their significant metabolic benefits, including weight loss and improved glycemic control. The aim of the study was to evaluate the effect of submaximal doses of long-lasting GLP-1RA semaglutide on selected biomarkers of obesity-related inflammation, adipocytokines levels and metabolism in a real-world population of obese patients. Methods: We performed a prospective, observational study involving 32 adult patients (11 men, 21 women; mean age 49 ± 12 years; BMI 40.5 ± 7.3 kg/m²) treated with submaximal doses of semaglutide over 12 weeks, together with hypocaloric diet and increased physical activity based. We analyzed selected biomarkers including insulin, leptin, ferritin, resistin, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) before and after three months of treatment. Results: We observed significant reductions in weight, BMI, waist circumference, insulin and leptin levels (all p < 0.001). On the other hand, no significant changes were recorded in ferritin (p = 0.806), IL-6 (p = 0.607), TNF-α (p = 0.633), resistin (p = 0.250) or PAI-1 (p = 0.134) levels. Correlation analyses revealed the correlation between IL-6 and adiposity indices (BMI, waist circumference) both before and after treatment. Ferritin and PAI-1 levels positively correlated with waist circumference, while resistin showed a negative correlation with central obesity. Conclusions: Submaximal-dose GLP-1 RA therapy was associated with significant improvements in metabolic parameters and adipokine regulation, but did not affect systemic inflammatory markers within 12 weeks. Future studies with larger cohorts and longer follow-ups are needed to clarify the associations.