Diabetes/Weight Loss Med Linked to Repeat Spinal Surgery

CHICAGO — The diabetes/weight loss drug semaglutide is associated with a significantly greater risk for repeat operations in patients with diabetes who require lumbar surgery, a new study suggests.

The risk for additional surgeries was even higher among patients taking the popular weight loss and diabetes drug for longer periods of time.

Investigators say the study provides the first evidence on the impact of semaglutide on spine surgery. 

"The expectation was [that] we would see patients doing better after surgery, less wound complications, and other things, and in our diabetic patients we did not see that and saw increased odds of needing additional surgeries," investigator Syed I. Khalid, MD, neurosurgery resident at University of Illinois Chicago, told Medscape Medical News.

The findings were presented on May 3 at the American Association of Neurological Surgeons (AANS) 2024 Annual Meeting.

Additional Surgery at Year 1

The new study used the all-payer Mariner database to identify patients aged 18-74 years with type 2 diabetes who underwent elective one- to three-level transforaminal lumbar interbody fusions (TLIFs) between January 2018 and October 2022. 

Patients were matched in a 3:1 ratio for age, sex, hypertension, obesity, smoking history, chronic kidney disease, osteoporosis, insulin use, and spinal fusion level, resulting in 447 patients with semaglutide use and 1334 with no semaglutide use. More than half (56%) were female, 62% used insulin, and 81% underwent single-level TLIF.

Total medical complications were higher in the semaglutide group, at 13.4%, compared with 7.7% in the no-semaglutide group (odds ratio [OR], 1.85). This was driven by higher rates of urinary tract infection (6.7% vs 2.5%) and acute kidney injury (6.3% vs 3.9%), two complications observed with semaglutide in other studies, Khalid said.

Total surgical complications, however, were lower in patients taking semaglutide, at 3.8% vs 5.2% in those who did not (OR, 0.73). 

Patients taking semaglutide vs those who were not using semaglutide had fewer wound healing complications (5 vs 31), hematoma (1 vs 9), surgical-site infections (12 vs 44), and cerebrospinal fluid leaks (2 vs 3).

Still, people taking semaglutide were nearly 12 times more likely to have an additional lumbar surgery at 1 year than did those who did not use the drug (27.3% vs 3.1%; OR, 11.79; 95% CI, 8.17-17.33).

Kaplan-Meier plots revealed a striking divergence of these populations when semaglutide exposure for more than or less than 9 months was examined (log-rank P < .0001).

Currently under review for publication, this study provides the first evidence on the impact of semaglutide on spine surgery, Khalid said. A second follow-up paper, also under review, looked only at patients with patients morbidly obesity without diabetes who had taken semaglutide for weight loss. 

"In nondiabetic, morbidly obese patients undergoing spine surgery, we see a similar trend," Khalid said.

Sarcopenia the Cause?

The additional surgeries were primarily extensions of constructs, with additional surgery and fusion at more levels, Khalid noted. 

"The idea is that it could be the fact there is sarcopenia or muscle loss that's taking place in conjunction with fat loss that's causing that to happen," Khalid said.

The mechanism remains speculative, but evidence from other areas examining frailty states has shown that those patients have weaker bones, sarcopenia, and worse outcomes with spine surgery, he noted. 

The investigators plan to use artificial intelligence to evaluate changes in body composition after semaglutide use in patients who underwent imaging prior to spine surgery or even before back pain occurred. Because these medications are uptitrated over time, follow-up studies will also look at whether this change takes place with a certain dose, Khalid added. 

On the basis of the current analysis of generic semaglutide alone, it's not possible to say whether the use of other glucagon-like peptide 1 (GLP-1) receptor agonists will result in similar findings, but "the odds of a class effect are high," Khalid said. 

Commenting on the findings for Medscape Medical News, Walavan Sivakumar, MD, director of neurosurgery at Pacific Neuroscience Institute, Los Angeles, noted that the timing of surgery is already an issue for patients taking semaglutide and other GLP-1 receptor agonists following recent guidance from the American Society of Anesthesiologists that suggests stopping GLP-1 receptor agonists prior to elective surgery to reduce the risk for complications associated with anesthesia.

"It's an incredibly topical point and seems to be something showing up on a daily basis for clinicians all throughout neurosurgery," Sivakumar said. "It's thought-provoking and a great first start." 

Sivakumar also observed that frailty is a hot topic in all of neurosurgery. "That's a major, major point that's showing an impact on all surgical outcomes and it's being heavily studied in the neurosurgical subsets right now. So that's definitely a possible correlating factor."

Khalid reported no financial relationships. Sivakumar reported serving as a consultant for Stryker. 

Patrice Wendling is a medical journalist based in Chicago.