GLP-1 Receptor Agonists Not Linked to Post-Op Respiratory Complications

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A retrospective study challenges preoperative withholding of GLP-1 RAs in diabetes patients undergoing surgery, citing no increased risk of postoperative respiratory complications.

Anjali Dixit, MD, MPH | Credit: Stanford Medicine

Anjali Dixit, MD, MPH
Credit: Stanford Medicine

A new study is adding to the discussions around whether or not patients with type 2 diabetes should discontinue use of GLP-1 receptor agonists before surgery.

Results of the study, which were published less than a year after the American Society of Anesthesiologists (ASA) recommended preoperative withholding of GLP-1 receptor agonists, fly in the face of recommendations and indicate there was no increased risk of postoperative respiratory complications associated with use prior to surgery.1,2

“Given increasing use of GLP-1 RAs, larger-scale evaluations of their perioperative risks are needed; however, a randomized trial of preoperative GLP-1 RA withholding may not be feasible,” wrote investigators.1 “Therefore, we used a claims database to evaluate the risk of postoperative respiratory complications among patients with diabetes and a prescription fill for GLP-1 RAs who underwent emergency surgery because these patients would be unlikely to withhold their medication in accordance with guidelines.”

On June 29, 2023, the ASA released guidance calling for patients to consider holding GLP-1 receptor agonists on the day of the procedure/surgery and for patients on weekly dosing to consider holding GLP-1 receptor agonists for a week prior. In a statement from the ASA announcing the publication of new guidance, the organization noted the recommendations came as the result of anecdotal reports purporting an association of delayed gastric emptying with use of GLP-1 receptor agonists and increased risk of regurgitation and pulmonary aspiration during general anesthesia and deep sedation.2

With no end in sight for the growing demand of GLP-1 receptor agonist therapies, a team of 5 led by Anjali Dixit, MD, MPH, a pediatric anesthesiologist at Stanford Medicine, launched the current study to explore associations between postoperative respiratory complication Among patients with diabetes and a prescription fill for GLP-1 receptor agonist who underwent emergency surgery. Investigators pointed out their study was designed as an analysis of a claims database as a randomized trial may not be feasible. Investigators also pointed out patients undergoing emergency surgery were identified as the subjects of interest as these patients would be unlikely to withhold medication in accordance with the ASA guidelines.1

Types of Emergency Surgery Included

Laparoscopic appendectomy
Laparoscopic cholecystectomy
Operative management of traumatic hip fracture
Colectomy for diverticulitis
Operative management of adhesive small bowel obstruction
Operative management of ovarian torsion
Operative management of testicular torsion
Operative management of ectopic pregnancy
Operative management of incarcerated or strangulated hernia
Laparoscopic or open repair of perforated peptic or duodenal ulcer
Transurethral intervention for nephrolithiasis
Upper endoscopy for foreign body removal
Upper endoscopy for management of bleeding peptic or duodenal ulcer

The Merative MarketScan Commercial Database was chosen as the data source for the analysis. Investigators performed a search of patients with type 2 diabetes and a GLP-1 RA prescription fill who had undergone any of 13 emergency surgeries between January 1, 2015, and December 31, 2021. For the purpose of analysis, the comparator group was composed of patients with diabetes and at least 1 fill for a non-GLP-1 receptor agonist antidiabetic agent.1

The investigators' final sample included 23,679 patients. Among these, 14.8% (n=3502) had a GLP-1 receptor agonist fill. Compared to those without a GLP-1 receptor agonist fill, those with a fill were more likely to be male, use more antidiabetic agents, and have concomitant obesity. The most common type of surgery indicated, for both groups, was transurethral intervention.1

The primary outcome of interest for the study was a composite of aspiration pneumonitis, postoperative respiratory failure, and/or admission to the intensive care unit through 7 postoperative days. Investigators noted multivariable logistic regression was used to estimate associations, with the fully adjusted model adjusted for demographic characteristics, indicators of diabetic severity including the Diabetes Complications Severity Index, Elixhauser comorbidities, and fixed effects for year and surgery type.1

Upon analysis, results indicated the overall incidence of postoperative complications was 3.5% among those with a GLP-1 receptor agonist fill and 4.0% in the non-GLP-1 receptor agonist group (Odds Ratio [OR], 0.85; 95% Confidence Interval [CI], 0.70 to 1.04; P = .12). In adjusted analysis, results indicated there was no significant difference in the incidence of postoperative respiratory complications between these 2 groups (adjusted OR, 1.03; 95% CI, 0.82 to 1.29; P = .80). Investigators highlighted these findings were consistent with further adjustment in secondary analyses.1

Investigators called attention to limitations within their study to consider when interpreting results. These limitations included being restricted to commercially insured patients, being unable to measure preoperative duration of GLP-1 receptor agonist use, lack of information on adherence, and not including GLP-1 receptor agonists fills for weight loss alone.1

“Results of this study suggest that liberalizing the withholding guidelines for GLP-1 RAs preoperatively should be considered,” investigators concluded.1

References:

  1. Dixit AA, Bateman BT, Hawn MT, Odden MC, Sun EC. Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications. JAMA. Published online April 22, 2024. doi:10.1001/jama.2024.5003
  2. Campbell P. Asa urges withholding GLP-1 RA therapy prior to elective procedures. HCP Live. July 14, 2023. Accessed April 25, 2024. https://www.hcplive.com/view/asa-urges-withholding-glp-1-therapy-prior-to-elective-procedures.
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