Preoperative Glucagon-Like Peptide-1 Receptor Agonists and Postoperative Outcomes: An Observational Analysis

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are increasingly prescribed for type 2 diabetes (T2DM) management with demonstrated benefits on glycemic control, cardiac outcomes, and weight reduction but further study is needed to establish the impact of GLP-1 RAs on perioperative outcomes.

We conducted an observational analysis with data between June 1, 2013, to June 1, 2023, using an electronic health record database (TriNetX Research Network) before the 2023 American Society of Anesthesiologists guidance to hold GLP-1 RAs preoperatively. Adult surgical patients with T2DM having anesthesia were propensity-score matched 1:1 by surgery type, patient characteristics, diabetic biomarkers, and risk factors for postoperative morbidity. We compared GLP-1 RA use with (1) metformin, (2) sodium-glucose cotransporter 2 inhibitors (SGLT2i), or (3) dipeptidyl peptidase-4 inhibitors (DPP4i). Each group did not have concomitant use of the comparator. Outcomes were 14-day postoperative mortality, aspiration pneumonitis, bacterial pneumonia, emergency intubation, acute kidney injury, stroke, acute myocardial infarction (MI), and major adverse cardiovascular events (MACE) as defined by a composite of mortality, MI, or stroke.

Preoperative GLP-1 RA use was associated with reduced mortality (0.98% vs. 2.20%, risk ratio (RR) 0.44 [95% confidence interval 0.31-0.64], Padj 0.0002) when compared to metformin use. Compared to SGLT2is, GLP-1 RAs were associated with numerical difference in MACE (3.86% vs. 5.03%, RR 0.77 [0.60-0.98], Padj 0.13). When compared with DPP4is, GLP-1 RAs were associated with decreased postoperative mortality (1.84% vs. 2.89%, RR 0.63 [0.45-0.89], Padj 0.04) and bacterial pneumonia (0.85% vs. 1.80%, RR 0.47 [0.29-0.76], Padj 0.02).

Preoperative GLP-1 RA use was associated with lower short-term postoperative mortality and reduced morbidity compared with metformin and DPP4is, and no increased aspiration risk compared to any other drug class. Although these findings suggest perioperative benefits of GLP-1 RAs, confirmation in prospective studies is needed to guide evidence-based management strategies.