Optimal Timing of GLP-1 Receptor Agonist Initiation in Patients with Obesity Eligible for Metabolic Bariatric Surgery

GLP-1-RAs and metabolic bariatric surgery (MBS) both improve outcomes in obesity. This study compares the effectiveness and safety of early GLP-1 initiation (≥ 3 months before) versus delayed initiation (≥ 1 month after) in adults undergoing MBS.

Retrospective cohort study using TriNetX. Adults with BMI > 30 were classified into GLP-1 RA after MBS, GLP-1 before MBS, and MBS-only cohorts. We performed 1:1 propensity score matching to compare each GLP-1 RA strategy to MBS only. Outcomes included mortality, CKD, 5-point MACE, osteoporosis, micronutrient deficiencies, SBO, internal hernia, and cholelithiasis and were assessed within 1 year. Cox proportional hazards models were used, excluding patients with pre-existing baseline conditions.

GLP-1 after MBS reduced the risk of death by 88% (HR 0.12, 95% CI 0.08-0.18) and 5-point MACE by 16% (HR 0.84, 95% CI 0.71-0.98) compared with MBS alone. In contrast, initiating GLP-1 RA before MBS reduced mortality by 80% (HR 0.20, 95% CI 0.14-0.30) only. GLP-1 after MBS also lowered the risk of micronutrient deficiency by 10% (HR 0.90, 95% CI 0.83-0.97), whereas GLP-1 RA before MBS increased this risk by 18% (HR 1.18, 95% CI 1.08-1.28). GLP-1 RA after MBS reduced the risk of SBO by 65% (HR 0.35, 95% CI 0.28-0.44), compared with a 39% reduction for GLP-1 RA before MBS (HR 0.61, 95% CI 0.49-0.76). GLP-1 RA use after MBS was associated with lower risks of internal hernia (HR 0.59, 95% CI 0.42-0.82) and cholelithiasis (HR 0.77, 95% CI 0.66-0.90), whereas GLP-1 RA before MBS did not show a significant difference for either outcome.

Initiating GLP-1 RA therapy after MBS appears to provide the most favorable balance of survival, cardiometabolic outcomes, and postoperative complications. These findings, particularly those related to mortality, should be interpreted with caution given the observational design and immortal time bias.