A total of 33,107 participants in 33 trials showed that GLP-1 receptor agonists may improve bone mineral density in patients with type 2 diabetes mellitus.
GLP-1 receptor agonists improved bone mineral density at the lumbar spine (0.052 g/cm), total hip (0.047 g/cm), and femoral neck (0.072 g/cm).
Bone resorption was reduced (β-CTX SMD -0.36), while markers of bone formation increased, potentially normalizing the abnormal bone remodeling seen in .
Long-term treatment with GLP-1 receptor agonists was associated with a 20% reduction in fracture risk (RR 0.80).
The effects on bone health may vary based on the type of GLP-1 receptor agonist used, patient characteristics, and duration of treatment.
Further studies focused specifically on bone health are needed for newer GLP-1 receptor agonist agents.
Simplified
INTRODUCTION: is a skeletal disorder that is characterized by increased fracture risk despite normal bone mineral density. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as important therapeutic agents for type 2 diabetes mellitus (T2DM), but their effects on diabetic bone disease were not studied nor investigated sufficiently in previous studies in the literature. We conducted a network meta-analysis to evaluate the differential effects of GLP-1 RAs on bone health outcomes in patients with T2DM.
METHODS: We performed a systematic review and network meta-analysis of randomized controlled trials evaluating GLP-1 RAs with bone-related outcomes in T2DM patients. Primary outcomes included changes in bone mineral density (BMD), bone turnover markers, and fracture incidence.
RESULTS: A total of 33 randomized controlled trials (33,107 participants) were included. GLP-1 RAs demonstrated improvements in BMD at the lumbar spine (0.052 g/cm[0.043-0.061]), total hip (0.047 g/cm[0.037-0.057]), and femoral neck (0.072 g/cm[0.060-0.084]), however BMD findings from studies less than 52 weeks require cautious interpretation per clinical densitometry standards. They reduced bone resorption (β-CTX SMD -0.36 [-0.53, -0.20]) while increasing formation markers, possibly normalizing the uncoupled remodeling characteristic of diabetic osteopathy. Long-term treatment was associated with reduced fracture risk by 20% (RR 0.80 [0.65-0.94]). 2 2 2
CONCLUSIONS: GLP-1 RAs may provide skeletal benefits in T2DM patients by addressing specific mechanisms underlying diabetic osteopathy. The skeletal effects appear to vary according to agent type, patient characteristics, and treatment duration, suggesting promising role for personalized approaches to therapy selection. When bone health is a concern, GLP-1 RAs may represent a beneficial therapeutic option that could simultaneously address both metabolic and skeletal outcomes in patients with T2DM, though further bone-specific studies is needed for newer agents.
Key numbers
0.052 g/cm
Increase in Lumbar Spine BMD
Mean increase at the lumbar spine with GLP-1 RA treatment.
20%
Fracture Risk Reduction
Long-term treatment with GLP-1 RAs associated with reduced fracture risk.
−0.41
Anti-resorptive Effect of Liraglutide
Standardized mean difference for bone resorption marker β-CTX with liraglutide.
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Declarations. Ethics approval and consent to participate: Ethical approvals were waived for this study, since this study did not involve direct human patients’ data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
