背景/目的:胰高血糖素样肽-1受体(GLP-1R)激动剂对钙稳态的影响尚不清楚。本研究旨在探讨GLP-1R激动剂使用与低钙血症和/或高钙血症风险之间的关系。以及其他临床结果。方法:一项回顾性队列研究使用来自TriNetX全球合作网络的去识别患者数据,包括15,655名服用GLP-1R激动剂的成年患者和15,655名倾向匹配的对照。结果包括低钙血症,高钙血症,紧急访问,住院治疗,心血管事件,和全因死亡率。结果:使用GLP-1R激动剂与低钙血症风险降低相关(2.7%vs.5.5%,RR0.49,95%CI:0.44-0.55),但高钙血症的风险增加(2.3%vs.1.1%,RR2.02,95%CI:1.69-2.42)。在治疗的前六个月,对低钙血症的影响最为明显。在个人代理人中,tirzepatide表现出最明显的效果,低钙血症风险降低63%,高钙血症风险增加85%.塞马鲁肽表现出类似的效果,而杜拉鲁肽和利拉鲁肽则表现出适度的效果。此外,GLP-1R激动剂的使用与急诊就诊风险降低相关(RR0.57,95%CI:0.54-0.60),住院率(RR0.40,95%CI:0.36-0.44),心血管事件,和全因死亡率(HR0.27,95%CI:0.21-0.36)。结论:GLP-1R激动剂对钙稳态表现出复杂的影响,降低低钙血症风险,同时增加高钙血症风险。除了钙调节,这些药物显著降低了医疗保健利用率,改善心血管结局,降低死亡率。需要进一步的研究来阐明个体GLP-1R激动剂不同效应背后的机制。尤其是替瑞哌肽,优化个性化治疗方法和长期安全性。
Background/Objectives: The effect of glucagon-like peptide-1 receptor (GLP-1R) agonists on calcium homeostasis is poorly understood. This study aimed to investigate the association between GLP-1R agonist use and the risk of hypocalcemia and/or hypercalcemia, as well as other clinical outcomes. Methods: A retrospective cohort study used de-identified patient data from the TriNetX Global Collaborative Network, including 15,655 adult patients prescribed GLP-1R agonists and 15,655 propensity-matched controls. Outcomes included hypocalcemia, hypercalcemia, emergency visits, hospitalizations, cardiovascular events, and all-cause mortality. Results: GLP-1R agonist use was associated with a reduced risk of hypocalcemia (2.7% vs. 5.5%, RR 0.49, 95% CI: 0.44-0.55) but an increased risk of hypercalcemia (2.3% vs. 1.1%, RR 2.02, 95% CI: 1.69-2.42). The effect on hypocalcemia was most pronounced during the first six months of treatment. Among individual agents, tirzepatide showed the most pronounced effect, reducing hypocalcemia risk by 63% while increasing hypercalcemia risk by 85%. Semaglutide demonstrated similar effects, while dulaglutide and liraglutide showed modest effects. Furthermore, GLP-1R agonist use was associated with reduced risks of emergency visits (RR 0.57, 95% CI: 0.54-0.60), hospitalizations (RR 0.40, 95% CI: 0.36-0.44), cardiovascular events, and all-cause mortality (HR 0.27, 95% CI: 0.21-0.36). Conclusions: GLP-1R agonists exhibit a complex influence on calcium homeostasis, reducing hypocalcemia risk while increasing hypercalcemia risk. Beyond calcium regulation, these medications significantly reduce healthcare utilization, improve cardiovascular outcomes, and decrease mortality. Further research is needed to elucidate the mechanisms behind the differential effects of individual GLP-1R agonists, particularly tirzepatide, to optimize personalized treatment approaches and long-term safety.