Letter to the Editor Regarding “Association Between Preoperative GLP-1 Receptor Analog Use and Postoperative Complications and Mortality Following Lumbar Fusion Surgery”

To the Editor,

We read with great interest the article by Kesaria et al ¹ evaluating the association between preoperative glucagon-like peptide-1 receptor analog (GLP-1 RA) use and outcomes after lumbar fusion surgery. The authors should be commended for examining a timely clinical question at the intersection of metabolic optimization and spine surgery. Their large propensity-matched analysis suggests lower risks of deep vein thrombosis, pulmonary embolism, sepsis, pneumonia, all-cause mortality, and pseudoarthrosis among GLP-1 RA users. These findings are encouraging; however, they also raise a practical translational question: does this association reflect a direct pharmacologic effect on fusion biology, broader metabolic improvement before surgery, or the healthcare engagement that often accompanies GLP-1 RA treatment?

This distinction is particularly relevant for pseudoarthrosis. GLP-1 signaling has been linked to osteoblast activity and bone-resorption pathways, although its net skeletal effect remains incompletely defined. ² At the same time, GLP-1 RA-associated weight loss may change mechanical loading and bone mineral density in ways that depend on nutritional status, resistance exercise, and treatment duration. ³ Thus, the reduction in nonunion may represent a composite of improved glycemic control, lower systemic inflammation, altered loading, and drug-related osteometabolic signaling rather than a uniform class effect. The timing of exposure is another clinically important issue. Defining use within 1 year before surgery is pragmatic, but it does not separate recent initiation from chronic stable therapy, perioperative interruption, or postoperative resumption. This distinction matters because multisociety guidance emphasizes individualized continuation or temporary withholding according to gastrointestinal symptoms and aspiration risk. ⁴ Future lumbar fusion studies could stratify patients by specific GLP-1 RA agent, dose, treatment duration, perioperative interruption/resumption, weight trajectory, HbA1c change, vitamin D status, and bone mineral density, while linking these variables to radiographic fusion and patient-reported outcomes. Kesaria et al have provided important evidence in a rapidly evolving area; refining the exposure phenotype may help determine whether GLP-1 RAs are potentially modifiable fusion-enhancing agents, markers of successful preoperative optimization, or one component of a broader prehabilitation pathway.