Li Xin, Li Yang, Lei Chen
Department of Nutrition General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Department of Geriatrics and Special Needs General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Int J Endocrinol. 2024 Sep 14;2024:1785321. doi: 10.1155/2024/1785321. eCollection 2024.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are an intriguing class of antihyperglycemic drugs for type 2 diabetes mellitus (T2DM). Such drugs not only play a primary role in regulating blood glucose levels but also exhibit additional pleiotropic effects, including potential impacts on bone metabolism and fracture risk. However, the mechanism of such drugs is unclear. The purpose of this study was to evaluate the effect of GLP-1 RAs on bone metabolism in T2DM.
From database inception to May 1, 2023, the searches were conducted on multiple databases such as Web of Science, Embase, PubMed, CNKI, the Cochrane Library, Wanfang, and VIP. We systematically collected all randomized controlled trials of bone metabolism in patients with T2DM treated with GLP-1 RAs. The quality evaluation was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. Data extraction was analyzed using Review Manager 5.4 software, and funnel plots were drawn to evaluate publication bias.
Twenty-six randomized controlled trials that met the inclusion criteria were included, involving a total of 2268 participants. In this study, compared to other antidiabetic drugs or placebo, GLP-1 RAs were found to significantly increase serum calcium (mean difference (MD) = 0.05, 95% confidence interval (CI) (0.01, 0.09), = 0.002], bone alkaline phosphatase [standardized MD (SMD) = 0.76, 95% CI (0.29, 1.24), and = 0.001), and osteocalcin (SMD = 2.04, 95% CI (0.99, 3.08), and = 0.0001) in T2DM. Specifically, liraglutide increased procollagen type 1 N-terminal propeptide (SMD = 0.45, 95% CI (0.01, 0.89), and = 0.04). GLP-1 RAs were also associated with a reduction in cross-linked C-terminal telopeptides of type I collagen (SMD = -0.36, 95% CI (-0.70, -0.03), and = 0.03). In additionally, GLP-1 RAs increased lumbar spine bone mineral density (BMD) (SMD = 1.04, 95% CI (0.60, 1.48), and < 0.00001) and femoral neck BMD (SMD = 1.29, 95% CI (0.36, 2.23), and = 0.007).
GLP-1 RAs can not only improve BMD in the lumbar spine and femoral neck of patients with T2DM but also protect bone health by inhibiting bone resorption and promoting bone formation. . PROSPERO, identifier CRD42023418166.
胰高血糖素样肽-1受体激动剂（GLP-1 RAs）是一类用于治疗2型糖尿病（T2DM）的抗高血糖药物，备受关注。这类药物不仅在调节血糖水平方面起主要作用，还具有其他多效性作用，包括对骨代谢和骨折风险的潜在影响。然而，此类药物的作用机制尚不清楚。本研究的目的是评估GLP-1 RAs对T2DM患者骨代谢的影响。
从数据库建立至2023年5月1日，在Web of Science、Embase、PubMed、中国知网、Cochrane图书馆、万方和维普等多个数据库进行检索。我们系统收集了所有用GLP-1 RAs治疗T2DM患者骨代谢的随机对照试验。根据Cochrane干预措施系统评价手册进行质量评估。使用Review Manager 5.4软件进行数据提取分析，并绘制漏斗图以评估发表偏倚。
纳入了26项符合纳入标准的随机对照试验，共涉及2268名参与者。在本研究中，与其他抗糖尿病药物或安慰剂相比，发现GLP-1 RAs可显著提高T2DM患者的血清钙[平均差（MD）=0.05，95%置信区间（CI）（0.01，0.09），P=0.002]、骨碱性磷酸酶[标准化MD（SMD）=0.76，95%CI（0.29，1.24），P=0.001]和骨钙素（SMD=2.04，95%CI（0.99，3.08），P=0.0001）。具体而言，利拉鲁肽可增加I型前胶原N端前肽（SMD=0.45，95%CI（0.01，0.89），P=0.04）。GLP-1 RAs还与I型胶原交联C端末肽的降低有关（SMD=-0.36，95%CI（-0.70，-0.03），P=0.03）。此外，GLP-1 RAs可增加腰椎骨密度（BMD）（SMD=1.04，95%CI（0.60，1.48），P<0.00001）和股骨颈骨密度（SMD=1.29，95%CI（0.36，2.23），P=0.007）。
GLP-1 RAs不仅可改善T2DM患者腰椎和股骨颈的骨密度，还可通过抑制骨吸收和促进骨形成来保护骨骼健康。PROSPERO标识符：CRD42023418166。
