Glucagon-like peptide-1 receptor agonist and post-operative opioid consumption in gynecologic surgery.

OBJECTIVE

Glucagon-like peptide-1 receptor agonists are increasingly prescribed for diabetes and obesity among patients undergoing gynecologic surgery. Beyond metabolic effects, glucagon-like peptide-1 receptors are expressed in the central nervous system and are implicated in nociception, reward processing, and neuroinflammatory signaling, suggesting a potential impact of glucagon-like peptide-1 receptor agonist exposure on opioid requirements. This study evaluated whether pre-operative Glucagon-like peptide-1 receptor agonist use is associated with reduced post-operative opioid consumption and differences in post-operative pain, length of stay, and 30-day post-operative complications.

METHODS

A single-center retrospective cohort study was conducted including patients undergoing gynecologic surgery between November 2023 and September 2025 within an Enhanced Recovery After Surgery pathway. The exposure was pre-operative Glucagon-like peptide-1 receptor agonist therapy, defined as an active prescription at surgical scheduling. The primary outcome was post-operative opioid use in morphine milligram equivalents in the post-anesthesia care unit and during admission. Secondary outcomes included highest post-anesthesia care unit pain score, length of stay, and 30-day complications according to the Clavien-Dindo complication. Analyses included unadjusted comparisons, multivariable linear regression, and propensity score matching.

RESULTS

Among 1320 patients (median age, 51 years), 140 (10.6%) were using Glucagon-like peptide-1 receptor agonist and had a significantly higher pre-operative comorbidity burden, including obesity, diabetes, higher Charlson Comorbidity Index, and ASA class III to IV, compared with non-users (all p < .05). No differences were observed between groups in opioid consumption in the post-anesthesia care unit (27.9 vs 25.8 morphine milligram equivalents) or during admission (16.4 vs 12.7 morphine milligram equivalents), pain scores (5.4 vs 5.3), length of stay (0.8 vs 0.9 days) or complications (15.7% vs 13.4%) (all p > .05). Results were consistent after propensity score matching. In multivariable analysis, obesity was independently associated with higher opioid consumption (β 4.01, p = .019).

CONCLUSIONS

Pre-operative Glucagon-like peptide-1 receptor agonist use was not associated with reduced post-operative opioid requirements in a cohort managed under an Enhanced Recovery After Surgery program. Despite greater baseline comorbidity among patients using glucagon-like peptide-1 receptor agonists, short-term post-operative outcomes were similar, without increased complications.