S764 Effectiveness of Early vs Delayed GLP-1 Receptor Agonist Initiation Following Bariatric Procedures: A Meta-Analysis of Randomized Controlled Trials

Introduction: GLP-1 receptor agonists (GLP-1 RAs) and bariatric procedures (BPs) are key strategies in the treatment of obesity. While both are effective individually, the optimal timing for initiating GLP-1 RAs following BP remains unclear. This meta-analysis evaluates the efficacy of early (≤8 weeks) versus delayed (>8 weeks) initiation of GLP-1 RAs after BPs. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane databases to identify randomized controlled trials (RCTs) comparing GLP-1 RAs to placebo or no intervention in patients who underwent BPs (surgical or non-surgical) and assessed whether early versus delayed treatment influenced outcomes. Primary outcomes included mean differences (MD) in total weight loss percentage (TWL%) and HbA1c% reduction. We used a random-effects model and I² statistic to assess pooled outcomes and heterogeneity. Results: Eight RCTs including 636 patients were analyzed: 350 received GLP-1 RAs, and 286 received placebo or no intervention. Among GLP-1 RA recipients, 173 started early treatment and 177 delayed treatment (mean time to treatment after BP in the delayed group was 57.4 months, SD = 29). Delayed GLP-1 RA use led to a greater TWL% (MD −7.24%, −11.05 to −3.42, P < 0.001), while early initiation was not beneficial (MD −2.46%, −6.73 to 1.80, P > 0.05). However, a pooled analysis of GLP-1 RA initiation irrespective of timing showed a significant benefit (MD −4.31%, −7.59 to −1.02, P = 0.01). HbA1c % reduction was also greater with delayed therapy (MD −0.31%, −0.47 to −0.16, P < 0.001) but not with early use (MD −0.01%, −0.17 to 0.15, P > 0.05). Leave-one-out sensitivity analysis revealed that excluding one study increased the TWL% benefit of early GLP-1 RA use (MD −4.33, −7.03 to −1.62; P < 0.01). In surgical BP patients, only delayed GLP-1 RAs led to a greater TWL% (MD –7.24%, –11.05 to –3.42); the delayed group also showed a significant reduction in HbA1c (MD –0.31%, –0.47 to –0.16; P < 0.001). Conclusion: Delayed initiation of GLP-1 RAs after BPs appears to yield greater benefits in TWL% and HbA1c% compared to early use. However, sensitivity analysis suggests a benefit from early therapy as well. The timing of GLP-1 RAs may influence metabolic outcomes and delayed initiation improved both TWL% and HbA1c% reduction. Further studies are needed to evaluate the efficacy of delayed GLP-1 RAs after non-surgical BPs.