Long-Term Effects of Semaglutide and Sitagliptin on Circulating IGFBP-1, IGFBP-3 and IGFBP-rp1: Results from a One-Year Study in Type 2 Diabetes

The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine the effects of semaglutide and dipeptidyl peptidase-4 inhibitor sitagliptin therapy on serum levels of IGFBP-1, IGFBP-3, and IGFBP-rp1, and to analyze their associations with anthropometric variables and markers of carbohydrate and lipid metabolism. In this prospective study, we enrolled 34 patients with type 2 diabetes mellitus (T2DM) on metformin monotherapy and 31 age-, sex- and BMI-matched controls. Among the patients, 18 received semaglutide, and 16 were treated with sitagliptin. Anthropometric and laboratory assessments were performed at baseline, 26 and 52 weeks. IGFBP levels were measured using ELISA. Both semaglutide and sitagliptin treatment significantly increased IGFBP-1 levels. IGFBP-3 levels were significantly decreased following sitagliptin therapy. No significant change in IGFBP-rp1 levels was observed with either treatment. Based on multiple regression analysis, the best predictors of IGFBP-1 were insulin and hsCRP, while the best predictor of IGFBP-3 was LDL-C level. Our findings suggest that semaglutide and sitagliptin may exert favorable effects on the GH/IGF-1 axis, potentially contributing to their beneficial metabolic outcomes in patients with T2DM.