Preoperative GLP-1 Receptor Agonist Use and Postoperative Opioid Outcomes in Elective Surgery

Preoperative GLP-1 Receptor Agonist Use and Postoperative Opioid Outcomes in Elective Surgery Ellias Hanna, BS1, Caitlin R. Priest, MD2,3, Vidhya Gunaseelan, MBA, MS, MHA3,4, Ryan Howard, MD2,3, Joshua Adkinson, MD5, Jennifer F. Waljee, MD, MPH, MS2,3,4,5 1Indiana University School of Medicine, South Bend, IN 2Department of Surgery, University of Michigan, Ann Arbor, MI 3Center for Healthcare Outcomes and Policy, Ann Arbor, MI 4Michigan Opioid Prescribing Engagement Network, Ann Arbor, MI 5Department of Surgery, Indiana University School of Medicine, Indianapolis, IN Objective To examine the association between preoperative glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and postoperative opioid outcomes among opioid-naïve adults undergoing elective surgery. Background GLP-1 receptor agonists modulate central reward pathways and have been associated with reduced substance use and opioid-related outcomes in preclinical and observational studies. However, whether preoperative GLP-1 RA use is associated with reduced postoperative opioid prescribing or persistent opioid use in surgical populations remains unclear. Methods We conducted a retrospective cohort study using the Merative MarketScan Commercial Database, including opioid-naïve adults aged 18–64 years undergoing one of the 20 most common elective surgical procedures between January 1, 2018, and June 30, 2023. The primary exposure was any GLP-1 RA prescription fill within 365 days prior to surgery. Secondary analyses evaluated patterns of preoperative GLP-1 RA exposure using K-means clustering based on prescription duration, continuity, and recency. Outcomes included perioperative opioid prescription fill, opioid refill, new persistent opioid use, and total opioid prescribing volume measured as morphine milligram equivalents (MMEs) within 30 and 90 days after discharge. Multivariable regression models adjusted for demographics, comorbidity burden, mental health and substance use disorders, chronic pain conditions, and surgical procedure type. Results Among 914,550 opioid-naïve surgical patients, 20,482 (2.2%) had preoperative GLP-1 RA exposure. In adjusted analyses, GLP-1 RA use was associated with higher odds of perioperative opioid prescription fill (adjusted odds ratio [aOR], 1.18; 95% CI, 1.13–1.22), opioid refill (aOR, 1.05; 95% CI, 1.01–1.10), and new persistent opioid use (aOR, 1.17; 95% CI, 1.05–1.30). Absolute differences in outcome rates were small, and adjusted mean MMEs at 30 and 90 days were nearly identical between GLP-1 RA users and non-users. Cluster-based analyses did not demonstrate a protective association for longer, more continuous, or more recent GLP-1 RA exposure. Conclusions Preoperative GLP-1 receptor agonist use was not associated with clinically meaningful reductions in postoperative opioid prescribing or opioid exposure among opioid-naïve surgical patients, suggesting limited utility of GLP-1 RAs as opioid-sparing agents in the perioperative setting.