Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients-Reference-Cited by-同舟云学术

Beyond Glycemic Control: GLP-1 Receptor Agonists and Their Impact on Calcium Homeostasis in Real-World Patients

Published:2024-08-19 Issue:16 Volume:13 Page:4896
ISSN:2077-0383
Container-title:Journal of Clinical Medicine
language:en
Short-container-title:JCM

Author:

Alenezi Bandar T.¹^ORCID,Elfezzani Nadra²,Uddin Rukhsana³,Patel Hinali⁴,Chester Sydney⁵,Abdelmaksoud Ahmed⁶,Hussein Mohammad H.⁷^ORCID,Zaitone Sawsan A.⁸^ORCID,Fawzy Manal S.⁹¹⁰^ORCID,Aiash Hani¹¹,Toraih Eman A.¹²¹³^ORCID

Affiliation:

1. Department of Pharmacology, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia

2. Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA

3. Women Medical and Dental College, Khyber Medical University Peshawar, Abbottabad 22080, Pakistan

4. School of Medicine, Louisiana State University, New Orleans, LA 70112, USA

5. School of Medicine, Tulane University, New Orleans, LA 70112, USA

6. Department of Internal Medicine, University of California, Riverside, CA 92521, USA

7. Department of Family Medicine, Ochsner Clinic Foundation, New Orleans, LA 70112, USA

8. Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia

9. Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia

10. Center for Health Research, Northern Border University, Arar 91431, Saudi Arabia

11. SUNY Upstate Medical University, Syracuse, NY 13210, USA

12. Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA

13. Medical Genetics Unit, Department of Histology and Cell Biology, Suez Canal University, Ismailia 41522, Egypt

Abstract

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.

Publisher

MDPI AG

Link

https://www.mdpi.com/2077-0383/13/16/4896/pdf

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