Incidence of Gastrointestinal Adverse Events and Healthcare Resource Utilization in Patients Using Glucagon-Like Peptide-1 Analogs: A Real-World Study

PURPOSE: Glucagon-like peptide-1 receptor agonists (GLP-1) are widely prescribed for diabetes mellitus (DM) and obesity. Growing concerns about gastrointestinal side effects (GI-AE) prompted this real-world study, to assess the incidence of GI-AEs and the associated healthcare burden in patients on GLP-1 s. METHODS: Using the TriNetX® network with 120 million patient records, patients with DM and obesity were grouped into GLP-1 and control cohorts. Propensity score matching (1:1) was performed using demographics, comorbidities, Hemoglobin-A1c, BMI, and other confounders. Incidence, number needed to harm (NNH), and Cox-proportional hazard ratios (HR) were used to compare outcomes at 1 year. RESULTS: After matching, 164,987 patients were included in each cohort. At one year, 31.9% of patients on GLP-1 therapy had GI-AEs (NNH 17.2), with incidence of nausea and vomiting, de-novo gastroesophageal reflux disease (GERD), and de-novo gastroparesis being 13%, 8.7%, and 0.7% respectively. GLP-1 use was associated with an increased risk of nausea and vomiting (HR 1.24 [1.21, 1.26]), GERD (HR 1.18 [1.14, 1.22]), proton pump inhibitor use (HR 1.15 [1.12, 1.19]), esophagitis (HR 1.24 [1.19, 1.30]), gastroparesis (HR 1.57 [1.43, 1.73]), drug-induced pancreatitis (HR 2.85 [1.82, 4.48]) and a decreased risk of bowel obstruction (HR 0.86 [0.80, 0.92]). No significant association was seen with cholecystitis (HR 1.10 [0.97, 1.15]) or choledocholithiasis (HR 1.07 [0.94, 1.21]). Esophagogastroduodenoscopy (EGD) utilization (HR 1.25 [1.20, 1.29]) was higher, but emergency room (ER) visits (HR 0.96 [0.95, 0.98]) and hospital admissions (HR 0.92 [0.91, 0.94]) were lower in the GLP-1 cohort. CONCLUSION: Nearly one-third of patients with DM and obesity on GLP-1 therapy reported GI-AEs, primarily nausea/vomiting and GERD. Providers should be aware of these events, given their association with increased EGD utilization but not higher ER visits or hospital admissions.