Evaluation of safety of preoperative GLP-1 receptor agonists in patients undergoing elective surgery: a systematic review, meta-analysis and meta-regression.

Background: Obesity remains a major global public health challenge, particularly among surgical patients, where it can be associated with increased perioperative and longer-term risk. While preoperative weight management strategies are often used to mitigate these risks, scalable interventions remain limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are an emerging pharmacological approach for weight loss, but their perioperative safety remains uncertain. This study aimed to assess the safety and efficacy of preoperative GLP-1 therapy in elective surgical systems.

Methods: In this systematic review and meta-analysis, we systematically searched PubMed, MEDLINE, Embase, and the Cochrane Library from database inception to March 31, 2025, for studies evaluating preoperative GLP-1 RA use in adults undergoing elective surgery, with no language restriction. The primary outcome was perioperative safety, defined as any complication within 90 days after surgery. The secondary outcome was preoperative weight loss. Both frequentist and Bayesian random-effects meta-analyses were conducted. A Bayesian hierarchical meta-regression was used to explore effect modifiers on the primary outcome. A risk-of-bias and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment were done to determine the certainty of the evidence. Final GRADE judgements were made by two independent reviewers, with consensus reached through discussion. Between-study heterogeneity was quantified using the I ² statistic and visualised using a standard forest plot. Potential publication bias and small study effects were assessed using visual inspection of funnel plots and Egger's test. This study is registered with PROSPERO, CRD420251027809.

Findings: A total of 21 studies, comprising 97,059 patients, met inclusion criteria; 31.9% (n = 30,981) received preoperative GLP-1 RA therapy. Most studies were single-centre observational cohorts from high-income countries, with no randomised trials identified. Postoperative complications were reported in 12 studies, with no evidence of increased risk in GLP-1 users (pooled odds ratio: 0.78, 95% confidence interval: 0.59-1.05). The pooled estimate shows high heterogeneity (I ² = 73%). Bayesian meta-analysis yielded consistent findings (posterior mean OR: 0.78; 95% credible interval: 0.57-1.12). Meta-regression identified no statistically significant modifiers of treatment effect to explain the heterogeneity. The overall GRADE assessment for certainty of evidence was very low. In studies reporting weight loss, preoperative GLP-1 RA use was associated with weight loss of up to 16.7 kg or 6.0 kg/m² over six months, though reporting varied across studies.

Interpretation: Preoperative GLP-1 RA therapy may support clinically meaningful weight loss without a clear signal of increased perioperative risk, offering a potentially scalable strategy for surgical optimisation. However, the certainty of current evidence is very low, with most studies observational in design and at risk of bias. Amid rising global obesity rates and mounting surgical backlogs, the role of GLP-1RAs in perioperative care remains a critical unanswered question. Robust randomised trials are needed to establish their clinical value, cost-effectiveness, and implementation potential across diverse surgical systems. Prioritisation by funders and policymakers are needed as part of broader health policy agendas to improve population health and health system resilience.

Funding: NIHR Doctoral Research Fellowship and NIHR Exeter Biomedical Research Centre Senior Investigator Fellowship.