AHMAD, SUMERA R

Abstract RATIONALE: Critical illness has been shown to disrupt gastrointestinal function, and patients admitted to the intensive care unit (ICU) often experience constipation, aspiration, ileus, and small bowel obstruction. Glucagon-like peptide 1 receptor agonists (GLP-1RA) have become increasingly prevalent in the treatment of type 2 diabetes mellitus and obesity. Pharmacovigilance studies suggest that use of GLP-1RAs may be associated with increased risk of clinically significant gastrointestinal effects. In this study, we assessed whether pre-ICU use of GLP-1RA for either diabetes or obesity was associated with adverse gastrointestinal outcomes. METHODS: This was a retrospective matched cohort study of patients with underlying obesity or diabetes admitted to a Mayo Clinic Medical ICU from 9/1/2018-12/31/2023. Patients who started GLP-1RA within <30 days or stopped them >30 days before admission were excluded. Out of 33,104 eligible patients, we identified 1,549 GLP-1RA exposed patients and matched these to three controls each based on age (±10), sex, body mass index (±5), presence of obesity, diabetes and complications, comorbidities associated with decreased motility, smoking status, alcoholism, abdominal surgeries, Apache score (±20), and Charlson comorbidity index (CCI). Development of gastrointestinal dysfunction (determined by ICD codes) and hospital- and ICU- free days were the outcomes. Conditional logistic regression and mixed linear models were used for the analyses. RESULTS: The final, matched cohort included 6,196 patients. Most patients were male (56.3%), the median age was 66 years (IQR 58-74), 69.9% had a diagnosis of obesity, and 97.5% had a diagnosis of diabetes. Of the patients, 22.9% had a history of abdominal surgery during their lifetime and 30% had surgery within 30 days of admission. When comparing GLP-1RA exposed and non-exposed patients, significant differences were noted in use of motility altering medications (p=0.001, OR 6.75, CI 2.11-21.56), BMI (p<0.001, estimate=0.6, CI 0.47-0.72), and APACHE score (p<0.001, estimate=14.75, CI14.45 – 15.06). Univariable analysis showed that rates of constipation, impaction, and nausea/vomiting were significantly higher among GLP-1RA exposed patients admitted to the ICU, while rates of obstruction were significantly lower (Table 1). After adjusting for APACHE score, only nausea/vomiting remained statistically significant. After controlling for APACHE, GLP-1RA use was associated with an increased number of hospital free days (Table 1). CONCLUSIONS: Our research suggests that in the medical ICU population, GLP-1RA use is unlikely to be associated with adverse GI outcomes. Furthermore, GLP-1RA may be associated with overall hospital length of stay but not ICU length of stay.