Perioperative glucagon-like peptide-1 receptor agonist exposure and persistent postoperative opioid use among adults with type 2 diabetes mellitus: a propensity score-matched cohort study

Persistent postoperative opioid use remains an important perioperative concern, particularly in adults with type 2 diabetes, who may be more vulnerable to adverse postoperative recovery. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may influence postoperative recovery through metabolic and inflammatory pathways, but their association with longer-term pain-related outcomes after surgery remains uncertain. We conducted a nationwide propensity score-matched cohort study using the TriNetX U.S. Collaborative Network. Adults with type 2 diabetes undergoing surgery were classified according to baseline preoperative GLP-1RA exposure within the 90 days preceding surgery. The primary outcome was an administrative proxy for persistent postoperative opioid use, defined as at least one documented opioid prescription during postoperative days 91–365. Secondary outcomes included chronic postsurgical pain, initiation of naloxone therapy, and opioid use disorder during the same interval. Among the 279,250 matched pairs, persistent postoperative opioid use occurred in 15.01% of patients in the GLP-1RA group and 17.44% of matched controls, corresponding to an absolute risk difference of 2.43% (95% confidence interval [CI] 2.24% to 2.62%) and a relative risk [RR] of 0.86 (95% CI 0.85–0.87; p < 0.0001). GLP-1RA users also had lower rates of chronic postsurgical pain (RR 0.78, 95% CI 0.73–0.84; p < 0.0001), naloxone initiation (RR 0.84, 95% CI 0.81–0.86; p < 0.0001), and opioid use disorder (RR 0.54, 95% CI 0.37–0.78; p = 0.0013). Among adults with type 2 diabetes undergoing surgical procedures, baseline preoperative GLP-1RA exposure was associated with lower pooled rates of persistent postoperative opioid use and other pain-related outcomes. However, the association with persistent postoperative opioid use varied by surgical category and anaesthetic technique, limiting uniform generalisation across surgical populations.