Letter to “Perioperative GLP-1 Receptor Agonist Use Is Associated With Reduced Revisions and Complications Following ACDF: A Propensity-Matched Analysis”

To the Editor,

We read with great interest the recent article by Kim et al ¹ entitled “Perioperative GLP-1 Receptor Agonist Use Is Associated With Reduced Revisions and Complications Following ACDF”. The authors should be commended for leveraging a large, propensity-matched cohort to address an increasingly relevant clinical question at the intersection of metabolic optimization and spinal fusion outcomes. Their findings suggest that perioperative GLP-1 receptor agonist (GLP-1RA) therapy may confer meaningful reductions in pseudarthrosis, revision rates, dysphagia, and healthcare utilization among patients with type 2 diabetes undergoing ACDF.

Beyond the limitations acknowledged by the authors, several additional aspects warrant further investigation.

First, although pseudarthrosis is an important surrogate for fusion success, radiographic nonunion does not invariably correspond to clinical failure, nor does radiographic fusion guarantee favorable functional outcomes. ² It remains unclear whether GLP-1RA use preferentially improves true biological fusion, early mechanical stability, or the alignment between radiographic findings and patient-reported outcomes. Future studies integrating imaging with validated functional metrics, such as the Neck Disability Index or pain scores, may help clarify whether GLP-1RA therapy meaningfully improves the radiographic–clinical concordance after ACDF.

Second, bone healing is a highly time-dependent biological process, yet GLP-1RA exposure in the present study was defined using a broad perioperative window. This approach does not distinguish between preoperative initiation, early postoperative continuation, or delayed initiation of therapy. It is plausible that GLP-1RAs exert differential effects across specific phases of bone remodeling, such as early inflammatory modulation vs later osteoblastic activity. Time-dependent exposure analyses or stratification by duration and timing of therapy may help identify an optimal therapeutic window for enhancing fusion biology.

Third, the interaction between GLP-1RA therapy and established fusion-enhancing strategies remains unexplored. Whether GLP-1RAs provide additive benefit in patients receiving autograft, allograft, or biologic augmentation or potentially mitigate the need for more aggressive fusion strategies in high-risk populations has important implications for surgical planning and value-based spine care. ³

Finally, although restricting the cohort to patients with T2DM strengthens internal validity, it raises questions regarding generalizability. The pleiotropic effects of GLP-1RAs on inflammation, body composition, and bone metabolism may not be exclusive to diabetic physiology. ⁴ Whether similar benefits extend to obese but non-diabetic patients or to individuals with adverse metabolic profiles short of overt diabetes warrants further investigation, ideally through stratification by metabolic phenotype rather than diagnosis alone.

In conclusion, Kim et al provide important evidence supporting an association between perioperative GLP-1RA use and improved outcomes after ACDF. Future studies focusing on temporal exposure patterns, interaction with fusion strategies, radiographic–functional concordance, and broader metabolic applicability will be critical in determining whether GLP-1RAs represent a modifiable perioperative intervention rather than a surrogate marker of optimized metabolic care.