Initiation of GLP-1 Receptor Agonists Treatment after Bariatric Metabolic Surgery and Major Adverse Cardiac Events

Introduction: Bariatric Metabolic Surgery (BMS) alone or Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) alone are known to reduce major adverse cardiovascular events (MACE). However, the benefit for primary prevention of MACE with use of GLP-1RA treatment after BMS is unclear. This retrospective cohort study assessed the associations of post BMS GLP-1RA treatment with first incidence of MACE/all-cause mortality, as well as with predicted cardiovascular (CVD) risk and body mass index (BMI) and hemoglobin-A1c (HbA1c) levels, among patients with obesity and diabetes. Methods: Adults who initiated GLP-1RA post-BMS were compared with individuals who did not. Groups were matched based on age, sex, BMI, HbA1c, years since BMS, and the nearest-neighbor propensity score for the probability of receiving GLP-1RA. Follow-up began at GLP-1RA initiation and ended on December 31, 2023. Results: The study population included 476 GLP-1RA initiators and 952 matched BMS-only patients (mean SD age: 48.7 9.5 years; 1046 73.2% women). GLP-1RA initiation after BMS was associated with reduction in BMI (-7.0%) and HbA1c (-13.0%) and higher diabetes remission (78.0% vs 61.6%). Ten-year predicted CVD risk was similar between users and non-users before treatment initiation (0.053%) but was significantly lower among users during follow-up (0.039% vs 0.046%). During a mean (SD) follow-up of 1.4 (0.8) years (maximum ~10.6 years), there were 12.7 per 1,000 person months (n=17) and 10.6 per 1,000 person months (n=7) new cases of MACE and all-cause mortality in the BMS-only and GLP-1RA post-BMS group, respectively. No overall statistically significant association was observed between initiation of GLP-1RA after BMS and MACE/all-cause mortality. However, significant interaction was observed with time since BMS (p=0.04), with a lower risk of MACE/all-cause mortality as the time from BMS increased. Conclusion: Initiation of GLP-1RAs after BMS was associated with lower BMI and HbA1c levels, higher diabetes remission, and reduced predicted CVD risk among patients with diabetes and obesity. Overall, GLP-1RA treatment after BMS did not further reduce the risk of MACE/all-cause mortality compared to BMS alone after a mean follow-up of 1.4 years. Given the observed time-dependent benefit of treatment after BMS, longer follow-up studies are needed to determine the optimal timing for initiation.