Il Diabete · Sep 3, 2026
https://ildiabeteonline.it/agonisti-recettoriali-glp-1-e-doppi-agonisti-gip-glp-1-alleati-metabolici-ma-quale-impatto-sullo-scheletro/
By Leanza G, Viola V, Bemporad J et al.
GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists have profoundly changed the treatment of type 2 diabetes (T2D) and obesity, expanding their role from glucose-lowering therapies to broader cardiometabolic and weight-loss interventions. As the number of patients exposed to these drugs continues to increase, their potential impact on bone metabolism and fracture risk deserves careful consideration. Preclinical evidence suggests that incretin signalling may directly modulate bone remodelling through effects on osteoblasts, osteoclasts, inflammation and energy metabolism. In humans, however, interpretation is complicated by concomitant improvements in glycaemic control, body weight reduction, loss of lean mass and changes in mechanical loading. Available meta-analyses do not indicate a clear increase in fracture risk with GLP-1 receptor agonists and suggest an overall neutral, or potentially favourable, skeletal profile, particularly in patients with T2DM. For high-dose semaglutide and tirzepatide, which produce greater weight loss, evidence is still evolving and warrants particular attention in older adults, postmenopausal women, patients with osteoporosis and those experiencing rapid weight reduction. Preservation of skeletal health during incretin-based therapy requires an integrated assessment of fracture risk, adequate protein, calcium and vitamin D intake, resistance exercise and monitoring of body composition. From a translational perspective, the key challenge is to maximise the cardiometabolic benefits of incretin-based therapies while preserving bone and muscle health.