Polypharmacy and Bone Health in Patients with Type 2 Diabetes Mellitus: A Narrative Review

Patients with type 2 diabetes mellitus (T2DM) commonly demonstrate reduced bone quality and elevated fracture risk rates despite having normal or elevated bone mineral density (BMD). Beyond the pathophysiological effect of diabetes, polypharmacy has emerged as a potential, yet underappreciated contributor of skeletal fragility. To explore this association, a thorough search of the literature was conducted using PubMed, Google Scholar, and Web of Science. and Scopus for articles published in English language until October 2025. Studies addressing diabetes, polypharmacy, bone health, and drug-related skeletal outcomes were identified and included. A divergent effect on bone health was evident in patients using antidiabetic agents, with thiazolidinediones, sulfonylurea and some insulin regimens increase fracture risk. Whereas metformin, incretinbased therapies and sodium-glucose co-transporter 2 inhibitors appear neutral or protective. Concerning non-antidiabetic medication used in T2DM, glucocorticoids, selective serotonin reuptake inhibitors, proton pump inhibitors and loop diuretics are among the drugs that worsen the bone architecture, causing increased fracture risk. On the other hand, statins, β-blockers, angiotensin converting enzyme inhibitors, thiazide diuretics and angiotensin receptor antagonists are bone protective. Such cumulative impact of polypharmacy involves drug-drug interactions, increased fall potential, and attenuation of antiresorptive therapy. Clinical interventions to prevent skeletal deterioration include periodic medications review, deprescribing of high-risk agents, calcium and vitamin D supplementation, and life-style modifications. Personalized and multidisciplinary strategies are essential to balance metabolic status with long-term skeletal preservation in patients with T2DM exposed to polypharmacy.