Tan Yimei, Liu Shuanghua, Tang Qizhi
Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China.
Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, No.16, Guicheng South Fifth Road, Foshan, 528200, Guangdong, China.
Acta Diabetol. 2025 Feb 22. doi: 10.1007/s00592-025-02468-5.
To 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.
From 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.
Twenty-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/cm, 95% CI 0.06 to 0.09, P < 0.00001), hip neck BMD (MD = 0.05 g/cm, 95% CI 0.03 to 0.08, P = 0.0001) and total hip BMD (MD = 0.06 g/cm, 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 β-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).
This 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 (β-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.
系统评价评估胰高血糖素样肽-1（GLP-1）受体激动剂对2型糖尿病患者骨折发生率、骨密度和骨代谢标志物影响的随机对照试验。
从数据库建立至2024年3月21日，在九个中英文数据库中进行检索。应用Cochrane偏倚风险工具评估潜在偏倚。使用RevMan 5.3和Stata 14.0进行数据分析。采用亚组分析和meta回归探索异质性来源，并使用漏斗图和Egger检验评估发表偏倚。
纳入25项研究。meta分析结果表明，GLP-1受体激动剂与骨折风险增加无显著相关性（RR = 0.80；95%CI 0.47至1.36；P = 0.41）。此外，腰椎骨密度（MD = 0.07g/cm，95%CI 0.06至0.09，P < 0.00001）、髋部颈骨密度（MD = 0.05g/cm，95%CI 0.03至0.08，P = 0.0001）和全髋骨密度（MD = 0.06g/cm，95%CI 0.04至0.07，P < 0.00001）的改善优于对照组。同样，GLP-1受体激动剂显著改善了I型前胶原氨基端前肽（SMD = 0.33，95%CI 0.07至0.59，P = 0.01）、骨钙素（MD = 1.46ug/L，95%CI 1.10至1.83，P < 0.00001）、25-羟基维生素D（SMD = 0.45，95%CI 0.06至0.83，P = 0.02）和骨特异性碱性磷酸酶（MD = 0.91ug/L，95%CI 0.19至1.63，P = 0.01），同时降低了β-胶原交联羧基末端肽（SMD = -0.34，95%CI -0.54至-0.14，P = 0.001）。对其他骨代谢标志物无显著影响，包括N-中段骨钙素（SMD = 0.43，95%CI 0.01至0.86，P = 0.05）、碱性磷酸酶（SMD = -0.00，95%CI：-0.25至0.25，P = 0.98）、钙（MD = 0.00mmol/L，95%CI -0.04至0.04，P = 0.94）和磷（MD = 0.02mmol/L，95%CI -0.04至0.07，P = 0.57）。
该meta分析表明GLP-1受体激动剂对骨折风险升高无显著影响。骨密度和某些骨转换标志物（β-胶原交联羧基末端肽、I型前胶原氨基端前肽、骨钙素、骨特异性碱性磷酸酶和25-羟基维生素D）有统计学显著改善。然而，由于存在一些局限性，需要进一步开展有足够随访时间的高质量临床研究以得出更明确的结论。
