Alenezi Bandar T, Elfezzani Nadra, Uddin Rukhsana, Patel Hinali, Chester Sydney, Abdelmaksoud Ahmed, Hussein Mohammad H, Zaitone Sawsan A, Fawzy Manal S, Aiash Hani, Toraih Eman A
Department of Pharmacology, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia.
Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
J Clin Med. 2024 Aug 19;13(16):4896. doi: 10.3390/jcm13164896.
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. 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. 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). : 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.
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。本研究旨在调查使用GLP-1R激动剂与低钙血症和/或高钙血症风险以及其他临床结局之间的关联。一项回顾性队列研究使用了来自TriNetX全球合作网络的去识别患者数据，包括15655例接受GLP-1R激动剂治疗的成年患者和15655例倾向匹配的对照。结局包括低钙血症、高钙血症、急诊就诊、住院、心血管事件和全因死亡率。使用GLP-1R激动剂与低钙血症风险降低相关（2.7%对5.5%，RR 0.49，95%CI：0.44-0.55），但与高钙血症风险增加相关（2.3%对1.1%，RR 2.02，95%CI：1.69-2.42）。对低钙血症的影响在治疗的前六个月最为明显。在各个药物中，替尔泊肽显示出最明显的效果，将低钙血症风险降低了63%，同时将高钙血症风险增加了85%。司美格鲁肽显示出类似的效果，而度拉鲁肽和利拉鲁肽显示出适度的效果。此外，使用GLP-1R激动剂与急诊就诊风险降低（RR 0.57，95%CI：0.54-0.60）、住院风险降低（RR 0.40，95%CI：0.36-0.44）、心血管事件和全因死亡率降低（HR 0.27，95%CI：0.21-0.36）相关。GLP-1R激动剂对钙稳态表现出复杂的影响，降低了低钙血症风险，同时增加了高钙血症风险。除了钙调节外，这些药物还显著降低了医疗保健利用率，改善了心血管结局，并降低了死亡率。需要进一步研究以阐明各个GLP-1R激动剂，特别是替尔泊肽的不同作用背后的机制，以优化个性化治疗方法和长期安全性。
