Real-World Effectiveness and Safety of GLP-1 Receptor Agonists in Patients with Weight Recurrence After Bariatric Surgery

ImportanceWeight recurrence occurs in nearly 20% of patients following metabolic and bariatric surgery (MBS) and can diminish long-term metabolic benefits. While glucagon-like peptide-1 receptor agonists and gastric inhibitory polypeptide receptor agonists (GLP-1 RA) have emerged as potential adjuvant therapies, evidence supporting their use is limited primarily to liraglutide with minimal real-world data on newer agents or population-level effectiveness. ObjectiveTo evaluate the effectiveness and safety of GLP-1 RA therapy compared to non-use among patients experiencing weight recurrence following MBS. Design, Setting, and ParticipantsThis retrospective new-user cohort study utilized from the OneFlorida+ Data Trust (2015-2024) to identify adults who underwent MBS and subsequently experienced [&ge;]10% weight recurrence from nadir weight. Propensity score matching based on BMI and clinical encounter timing, combined with inverse probability of treatment weighting, was used to minimize confounding. Of 1,098 patients who underwent MBS and experienced weight recurrence, the final weighted analytic cohort included 68 GLP-1 RA users and 131 non-users at 6 months, and 72 users and 139 non-users at 12 months. ExposureInitiation of any GLP-1 RA (dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, or tirzepatide) after MBS among patients with weight recurrence. Main Outcomes and MeasuresThe primary effectiveness outcome was percentage of recurrent weight lost at 6 and 12 months. Safety outcomes included composite gastrointestinal and surgical adverse events. ResultsGLP-1 RA use was associated with significantly greater mean weight recurrence loss compared to non-use at 6 months (9.6% vs 4.3%, p = 0.005) and 12 months (14.8% vs 8.1%, p = 0.017). Among individual agents, tirzepatide was associated with the largest reductions at both 6 and 12 months (25.1% vs 5.4% and 34.4% vs 8.8%, respectively; both p < 0.001). Liraglutide demonstrated a statistically significant difference at 12 months (18.3% vs 8.4%, p = 0.004), while semaglutide and dulaglutide were not associated with statistically significant differences at either time point. No significant differences in adverse event rates were observed between groups, with composite safety outcomes occurring in 47.1% of users versus 56.5% of non-users at 6 months (HR = 1.24, 95% CI: 0.92-1.68, p > 0.05). Conclusions and RelevanceUse of GLP-1 RA for the treatment of weight recurrence following MBS represents an effective option with sustained benefits through 12 months without increased risk of adverse events. These real-world findings support adjuvant GLP-1 RA use for managing weight recurrence following MBS across diverse patient populations. Key PointsO_ST_ABSQuestionC_ST_ABSDoes the use of glucagon-like peptide-1 and gastric inhibitory polypeptide receptor agonists (GLP-1 RA) for the treatment of weight recurrence after bariatric surgery lead to significant weight loss in real-world populations? FindingsIn this cohort study of 1,098 individuals who underwent bariatric surgery and experienced weight recurrence, use of GLP-1 RA was associated with significant loss of regained weight. MeaningUse of GLP-1 RA for weight recurrence after bariatric surgery represents a viable treatment option.