Title
The Impact of GLP-1 Agonists on Osteoporosis Risk in Diabetes Mellitus: A Retrospective Comparative Cohort Analysis Using TriNetX Database.
Authors
Hala Yousef 1, MD; Esra'a Alshdifat 1, MD; Reyad Al Jabiri 1, MD; Faiq Aldarabah 1, MD; Rami Al Jabiri 2, MS; Tasneem Zahra 1, MD
1 Lincoln medical center, Bronx, NY
2 October 6 University, Egypt MD
Introduction
Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) are well known for their role in treatment of type 2 diabetes mellitus (DM) and more recently, obesity. These drugs mimic the action of the naturally occurring hormone GLP-1, which is involved in regulating blood sugar levels. GLP-1 agonists work by stimulating insulin secretion in response to meals, inhibiting glucagon release (which helps control glucose production by the liver), and slowing gastric emptying, which helps with satiety. Recent evidence is pointing toward their effect on bone mineral density. In this study we aim to look further at their potential effects on bone metabolism and osteoporosis.
Methods
We conducted a retrospective cohort study using TriNetX, a federated global research network aggregating de-identified electronic medical records from large healthcare organizations. Adult patients with Diabetes Mellitus and HBA1C = 8 were included. Patients with a previous history of secondary causes of osteoporosis, such as thyrotoxicosis, Cushing’s syndrome, Malnutrition, use of systemic glucocorticoids and CKD were excluded. Patients who had a history of osteoporosis and intake of bisphosphonates before the start of treatment with GLP-1 were also excluded. Patients were stratified into two groups: those who received GLP-1 Agonists and those who did not. Propensity score matching (1:1) was performed to balance cohorts by age, sex, obesity, gonadal dysfunction (Menopause, Testicular hypofunction), Vitamin D deficiency, alcohol abuse and calcium malabsorption. The primary outcome was the incidence of osteoporosis followed at 5-, 10- and 15-year intervals. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated to compare event rates between groups at each interval.
Results
A total of 127,552 patients met the inclusion criteria, with 63,776 in each matched cohort. The mean age was 52.8 years in both groups. Female percentage was 44.6% in both groups. GLP-1 agonist-treated patients had a significantly lower risk of developing osteoporosis at all studied time intervals: 5 years (RR 0.651, 95% CI 0.578, 0.722), 10 years (RR 0.607, 95% CI 0.546,0.676), 15 years (RR 0.591, 95% CI 0.523, 0.658), all with p < 0.001.
Conclusion
Patients who received GLP-1 agonists had a significantly decreased risk of developing osteoporosis, even when confounding for other risk factors and causes of secondary osteoporosis at all time intervals. The benefits of GLP-1 agonists in the treatment of DM and obesity are well developed and proven, but the studies about their protective effect on bone metabolism and osteoporosis are scarce, promoting the need for further understanding of their molecular function and protective mechanisms on the bone.
References
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