Effect of GLP-1 receptor agonists on bone mineral density, bone metabolism markers, and fracture risk in type 2 diabetes: a systematic review and meta-analysis

AimTo systematically assess randomized controlled trials that evaluated the effect of glucagon-like peptide-1 (GLP-1) receptor agonists on fracture incidence, bone mineral density, and bone metabolism markers in individuals with type 2 diabetes. MethodsFrom database setup to March 21, 2024, a search was conducted across nine Chinese and English databases. The Cochrane Risk of Bias Tool was applied to assess potential bias. Data analysis was performed using RevMan 5.3 and Stata 14.0. Subgroup analysis and meta regression were employed to explore sources of heterogeneity, and publication bias was evaluated using funnel plots and Egger's test. ResultsTwenty-five studies were included. The results of the meta-analysis indicated that GLP-1 receptor agonist was not significantly associated with an increased risk of fracture (RR = 0.80; 95% CI 0.47 to 1.36; P = 0.41). Additionally, improvement in lumbar spine BMD (MD = 0.07 g/cm2, 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm2, 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm2, 95% CI 0.04 to 0.07, P < 0.00001) was superior to the control group. Similarly, GLP-1 receptor agonists significantly improved P1NP (SMD = 0.33, 95% CI 0.07 to 0.59, P = 0.01), OC (MD = 1.46 ug/L, 95% CI 1.10 to 1.83, P < 0.00001), 25-OH-D (SMD = 0.45, 95% CI 0.06 to 0.83, P = 0.02), and b-ALP (MD = 0.91ug/L, 95% CI 0.19 to 1.63, P = 0.01) while reducing beta-CTX (SMD = - 0.34, 95% CI - 0.54 to - 0.14, P = 0.001). There was no significant impact on other bone metabolism markers, including N-MID-OT (SMD = 0.43, 95% CI 0.01 to 0.86, P = 0.05), ALP (SMD = - 0.00, 95% CI: - 0.25 to 0.25, P = 0.98), Calcium (MD = 0.00 mmol/L, 95% CI - 0.04 to 0.04, P = 0.94) and Phosphate (MD = 0.02 mmol/L, 95% CI - 0.04 to 0.07, P = 0.57). ConclusionThis meta-analysis demonstrated no significant effect of GLP-1 receptor agonists on elevated fracture risk. There was a statistically significant improvement in BMD and certain bone turnover markers (beta-CTX, P1NP, OC, b-ALP, and 25-OH-D). However, due to some limitations, further high-quality clinical studies with sufficient follow-up time are needed to draw more definitive conclusions.