The emergence of GLP-1 agonists for the treatment of type 2 diabetes and obesity has reshaped the landscape of weight management. This raises an important question for the musculoskeletal community: What do weight loss drugs do to the skeleton?
Glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. semaglutide) are medications that mimic the endogenous incretin hormone GLP-1 to control blood glucose in type 2 diabetes, and to promote weight loss in obesity through appetite suppression and slowed gastric emptying. These drugs have had health benefits to diabetic and obese patients, improving metabolism and function of many organ systems, most notably reducing the risk of heart attack, stroke and death.
In general, rapid weight loss (whether intervention or disease induced) usually coincides with a reduction in bone mineral density (BMD), disruption of bone architecture and elevated fracture risk. However, clinical studies with GLP-1 agonists are less clear. In type 2 diabetes fracture risk varies between studies and the type of GLP-1 agonist used, but several clinical studies report reduction in fracture risk. The more recent approval for GLP-1 agonist use in non-diabetic obesity, means it may be a while before we understand the impact on fracture risk, particularly the long-term outcomes. The rapid ‘mainstream’ uptake of GLP-1 agonists coupled with the fact that cessation of these drugs is often followed by weight regain means that long-term use may become commonplace in society. Thus, highlighting the importance of understanding the impact to bone health.
The mechanisms behind this are far from simple, and will require insights from clinical and preclinical studies. While mechanical unloading following weight loss stimulates bone loss, there are many other factors that can contribute, including changes to bone marrow adipose signalling, exercise levels and skeletal muscle composition, hormones, nutrition, and metabolism. Deciphering the musculoskeletal impact of weight loss, and sustained use of GLP-1 agonists when patients are no longer obese, is critical for identifying approaches for protecting bone health.
Interested in learning more about the impact of weight loss on bone? Read a recent review by Liu et al. 2025 ‘Weight loss induced bone loss: mechanism of action and clinical implications’ published in Bone Research.