Semaglutide Exposure and its Association with Adverse Outcomes in Patients Undergoing TLIF for Lumbar Degenerative Disc Disease

Introduction: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type-2 diabetes. However, its effect on osteoclast activity and potential to induce weight-related muscle loss raises concerns about its impact on spinal surgical outcomes. As such, evaluating Semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions.

Methods: We analyzed data from patients with type-2 diabetes mellitus aged 18-74 who underwent short segment fusions (≤ 3 level) TLIFs between 2018 and 2022 using an all-payor database, MARINER. Patients were either exposed to Semaglutide or not. A comprehensive 1:1 exact matching was performed based on age, gender, comorbidity status, levels of surgery, and insulin dependence. Kaplan-Meier (KM) survival curves and log-rank testing were performed to study the probability of additional surgery within one year. Duration of therapy KM analysis was also conducted to understand how Semaglutide use duration impacted outcomes.

Results: After the 1:1 matching, 900 patients were identified, with an equal distribution between the Semaglutide-exposed and non-exposed cohorts. The majority of patients in both groups were aged 55-65, and 59.3% were female (p>.99). Analysis showed that the likelihood of undergoing an additional surgery within one year post-TLIF was significantly elevated in the Semaglutide-exposed group compared to the non-exposed group (odds ratio 7.43, 95% CI 4.57-12.09). Kaplan-Meier survival analysis suggested a direct correlation between prolonged Semaglutide use and increased probability of subsequent surgeries within one year of the index TLIF, as illustrated by the diverging survival curves.

Conclusion : Semaglutide exposure appears to be associated with a higher likelihood of additional surgeries within one year post-TLIF, especially in patients on the medication for longer durations. While the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.