Semaglutide Users Were Nearly 12 Times More Likely to Need Repeat Spinal Fusion Surgery | Research

The takeaway

Diabetic patients on semaglutide who underwent spinal fusion surgery were 11.79 times more likely to require additional fusion surgery within one year compared to matched non-users.

OR 11.79
Semaglutide-exposed patients were nearly 12 times more likely to need additional lumbar fusion surgery within one year, with the risk increasing with longer drug exposure

What the researchers found

After 1:3 propensity score matching on 10 variables (age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking, osteoporosis, levels of surgery, and insulin dependence), the semaglutide-exposed group showed a dramatically higher odds of needing additional lumbar fusion surgery within one year: OR 11.79 (95% CI 8.17–17.33).

Kaplan-Meier survival analysis with log-rank testing confirmed a statistically significant divergence in the probability of additional surgery between cohorts (P < 0.001). The association was stronger in patients receiving semaglutide for longer durations, suggesting a dose-duration relationship.

Why it matters

Millions of people now take semaglutide for diabetes and obesity, and many of them will eventually need orthopedic surgery including spinal fusion. An odds ratio of nearly 12 for revision surgery is an extraordinary finding that could change surgical planning for these patients. If semaglutide impairs bone healing, surgeons may need to consider drug holidays before elective spinal surgery, and patients should be informed of this potential risk.

How the study worked

This retrospective matched cohort study used the MARINER all-payer database to identify patients aged 18–74 with type 2 diabetes who underwent short-segment (≤3-level) transforaminal lumbar interbody fusion (TLIF) between January 2018 and October 2022. Patients were classified as semaglutide-exposed or non-exposed. A comprehensive 1:3 matching was performed on 10 clinical variables. Primary outcome was additional lumbar fusion surgery within one year, analyzed using odds ratios, Kaplan-Meier survival curves, and log-rank testing.

What this study cannot tell us

This is a retrospective database study that can show association but not causation. Despite careful matching on 10 variables, unmeasured confounders could influence the results — for example, semaglutide users may have more severe or longer-duration diabetes, greater metabolic derangement, or other factors not captured in the database. The odds ratio of 11.79 is extremely large for an observational study, which could suggest residual confounding. The database may have coding limitations that affect patient classification. Specific bone density data, nutritional status, and vitamin D levels were not available.

How to read the evidence

This is a large retrospective matched cohort study using an all-payer database — providing real-world evidence with good statistical power. However, the observational design limits causal inference, and the extremely large effect size warrants cautious interpretation pending confirmation from prospective studies. Unmeasured confounding remains a significant concern.

When this study was published

Published in 2025, this is a very recent study addressing an urgent safety question as semaglutide use explodes worldwide. The findings are likely to prompt further investigation and potentially influence surgical planning guidelines.

The bigger picture

This study raises a critical safety question at the intersection of the GLP-1 agonist revolution and orthopedic surgery. GLP-1 receptors are expressed on osteoblasts and osteoclasts, and semaglutide's rapid weight loss can reduce mechanical loading on bones and cause muscle loss — both of which could impair bone healing. As GLP-1 drugs become the most prescribed medications globally, understanding their effects on bone biology and surgical outcomes is essential for patient safety across medical specialties.

Questions still open

Should patients discontinue semaglutide before elective spinal fusion surgery to allow bone metabolism to normalize?
Is the increased revision rate due to impaired bone fusion, muscle loss-related instability, or other mechanisms?
Do other GLP-1 receptor agonists (liraglutide, tirzepatide) show similar associations with impaired surgical bone healing?

Common questions

Why might semaglutide affect bone healing after spinal surgery?

There are several potential mechanisms. First, GLP-1 receptors are found on bone cells, and semaglutide may directly affect bone turnover — the balance between building new bone and breaking down old bone. Second, the rapid weight loss caused by semaglutide reduces the mechanical forces on bones that normally stimulate bone strengthening. Third, weight loss with GLP-1 drugs can include significant muscle loss, which may reduce spinal stability and put more stress on the fusion site. All of these factors could impair the bone growth needed for a successful spinal fusion.

Should patients stop taking semaglutide before spine surgery?

This study raises the question but can't definitively answer it — it shows an association, not proven causation. However, the nearly 12-fold increase in revision surgery is concerning enough that patients should discuss their semaglutide use with their spine surgeon before any fusion procedure. Some surgeons may recommend a drug holiday before elective surgery, though the optimal timing and whether this actually reduces risk hasn't been studied yet. This is an active area of investigation that will likely lead to updated surgical guidelines.

Read the original research

Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.

Journal of neurosurgery. Spine, 42(1), 1-8

View on PubMed ↗Publisher’s paper ↗

Citation

Khalid, Syed I; Massaad, Elie; Thomson, Kyle; Shin, John H. (2025). Semaglutide exposure and its association with adverse outcomes in diabetic patients undergoing transforaminal lumbar interbody fusion for lumbar degenerative disc disease.. Journal of neurosurgery. Spine, 42(1), 1-8. https://doi.org/10.3171/2024.6.SPINE24141