Research Letter
April 22, 2024
Preoperative GLP-1 Receptor Agonist Use and Risk of Postoperative Respiratory Complications
Anjali A. Dixit, Brian T. Bateman, Mary T. Hawn, et al
JAMA. 2024;331(19):1672-1673. doi:10.1001/jama.2024.5003
In June 2023, the American Society of Anesthesiologists issued guidelines recommending preoperative withholding of glucagon-like peptide 1 receptor agonists (GLP-1 RAs),1 used for type 2 diabetes management and weight loss. These guidelines, which have been questioned,2 arose from reports of delayed gastric emptying and pulmonary aspiration following induction of anesthesia in patients using GLP-1 RAs. Although preoperative medication guidelines can prevent complications, withholding medications can also result in adverse effects.3 Furthermore, associated logistical burdens can result in surgical cancellations, significant care delays, and financial losses from unused operating room time.4,5 These downsides are pronounced for GLP-1 RAs due to recommended withholding periods of up to a week. 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. 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.
Methods
We used administrative claims from the Merative MarketScan Commercial Database, a large national database of about 250 million individuals younger than 65 years enrolled in employer-sponsored health insurance plans. We evaluated all 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 (eTable 1 in Supplement 1). We restricted our sample to patients who had undergone surgery on the same day as an emergency department visit because these patients would be unlikely to have sufficient time to withhold their GLP-1 RA medication. Because patients with diabetes are at higher risk of postoperative respiratory complications,6 our comparison group comprised patients with diabetes and at least 1 fill for a non–GLP-1 RA antidiabetic agent. The outcome was a composite of aspiration pneumonitis, postoperative respiratory failure, and/or admission to the intensive care unit from 0 through 7 postoperative days (eMethods 1, eTable 2 in Supplement 1).
We assessed differences in characteristics between patients with vs without a GLP-1 RA fill using standardized mean differences (SMD), with SMD greater than 0.1 reflecting meaningful differences between groups. To estimate the association between having a fill for a GLP-1 RA preoperatively and postoperative respiratory complications, we used multivariable logistic regression adjusting for demographic characteristics, indicators of diabetic severity including the Diabetes Complications Severity Index, Elixhauser comorbidities, and fixed effects for year and surgery type (eMethods 1 in Supplement 1). Sensitivity analyses included narrowing the outcome to include only pulmonary aspiration and postoperative respiratory failure; reestimating the model using targeted maximum likelihood estimation, a double-robust method that may better approximate causal effects; and restricting the sample to surgeries with low risk of aspiration and postoperative complications (eMethods 2 in Supplement 1). Statistical inferences were based on 2-sided P < .05.
This study was approved by the Stanford University institutional review board with waiver of consent. Analyses were conducted using STATA version 17.0 and R version 4.2.3.
Results
Our final sample included 23 679 patients, 3502 (14.8%) of whom had a GLP-1 RA fill (Table 1). Those with a GLP-1 RA fill were more likely to be male, use more antidiabetic agents, and have diagnoses of obesity. Overall incidence of postoperative respiratory complications was 3.5% for those with a GLP-1 RA fill and 4.0% for those without (odds ratio [OR], 0.85; 95% CI, 0.70-1.04; P = .12). After adjustment, there was no significant difference in the incidence of postoperative respiratory complications between these 2 groups (adjusted OR, 1.03; 95% CI, 0.82-1.29; P = .80). Findings were robust to alternative specifications (Table 2).
Discussion
Preoperative use of GLP-1 RAs in patients undergoing emergency surgery was not associated with a higher risk of postoperative respiratory complications compared with patients not using GLP-1 RAs. Study limitations include being restricted to commercially insured patients, being unable to measure preoperative duration of GLP-1 RA therapy,3 and the lack of information about patient adherence to the medication. In addition, the study did not examine fills of GLP-1 RAs for weight loss alone. Results of this study suggest that liberalizing the withholding guidelines for GLP-1 RAs preoperatively should be considered.
