1683-P: Fracture Risk Associated with Tirzepatide: A Systematic Review and Meta-analysis of Randomized Controlled Trials and Real-World Evidence

Introduction and Objective: The impact of tirzepatide is substantial in reducing glucose and body weight, but its relevance to skeletal safety remains unknown. The purpose of this analysis is to evaluate the fracture risk of tirzepatide compared with controls in randomized trials and GLP-1 receptor agonists in real-world data. Methods: We searched systematically for randomized phase 2/3 trials that reported fracture outcomes and comparative observational studies. For the analyses involving trials, the tirzepatide dose groups were combined to avoid double-counting. We combined results with fixed-effect Peto odds ratios for rare events and hazard ratios estimated by inverse variance in the observational study. PROSPERO: CRD420261278843. Results: Eleven trials (N=10,240; tirzepatide n=6,357; control n=3,883) reported 50 fractures (37 vs 13; 0.58% vs 0.33%). Tirzepatide was associated with higher fracture odds (Peto OR 1.84, 95% CI 1.02-3.31; I2=25%; p=0.04). The retrospective study comparing tirzepatide with GLP-1 receptor agonists found no significant difference (HR 1.16, 95% CI 0.89-1.52; p=0.28). Conclusion: There were a few fractures in total. Pooled-data analysis in RCTs yielded an increased odds ratio for fractures in the tirzepatide group compared to the control groups, whereas real-world analyses did not reveal a significantly increased risk. More long-term studies, as well as fracture outcome studies, would be desirable.