2026 Southeastern Residency Conference

Title: Association between outpatient glucagon-like peptide-1 receptor agonist use and the incidence or severity of sepsis
Authors:

Primary: Mary Sizer
Secondary: Hanna Kim, Jinae Lee, Daniel B. Hall, John Carr, PharmD, Akshaya Arunkumar, Abigail Case. PharmD, Chelsea Keedy

Objective: To determine if outpatient GLP-1 RA is associated with a decreased risk of sepsis occurrence or severity.

Background:
Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) mimic the endogenous hormone involved in regulating blood glucose concentrations and appetite. These agents are approved in management of type 2 diabetes and have grown popular for weight management. Pre-clinical and clinical data found anti-inflammatory, antioxidant, and multiorgan protective effects from use, suggesting a potential protective effect in acutely ill patients. Inversely, preliminary data has also suggested an increase in mortality for critically ill patients on such agents. There is limited data that investigates this association. The purpose of this study is to evaluate the association between GLP-1 RA use and incidence and severity of sepsis.

Methods:
This retrospective cohort study investigated the association between outpatient GLP-1 RA therapy and both the incidence and severity of sepsis using Merative MarketScan Commercial Database insurance claims recorded between January 1, 2022 and December 31, 2024. The cohort included adults with BMI >30, hospitalization or emergency room visit, and diagnosis of pneumonia, urinary tract infection, diabetic foot infection or intraabdominal infection identified by ICD10 codes. Patients that were pregnant, had cancer, were on hospice, or diagnosed with diabetes or diabetic foot infection were excluded. Inclusion and exclusion criteria were examined for the 6-month period prior to the data of hospitalization/ER visit (the index date) and eligible patients were divided into a GLP-1 RA use group and a control group. Chronic therapy was defined as ≥ 90-day total supply filled within 6 months of the index date and identified using NDC codes. Those that did not meet this definition were placed in the control. For both sepsis incidence and severe sepsis incidence, propensity score weighted logistic regression was used with inverse probability of treatment weighting to estimate odds ratios quantifying the average treatment effects among the treated while controlling for baseline confounders including age, sex, BMI (30-39.9 vs. >=40), and all baseline comorbidities including chronic heart failure, chronic kidney disease, liver cirrhosis, AFib, dementia, chronic ischemic heart disease. Propensity scores were estimated using logistic regression and covariate balance was assessed using both the standardize mean difference (acceptable range of +/- 0.1) and Kolmogorov-Smirnov (<0.05) criteria. Statistical inference was based on the nonparametric bootstrap implemented using 500 resampled datasets.

Results:
Of the 634,718 patients identified with a hospitalization/emergency room visit and concurrent infection, 22,267 patients fit eligibility criteria for the study. GLP-1 RA use accounted for 640 of those enrolled (2.87%) and 21,627 (97.1%) were enrolled into the comparator group. Baseline characteristics were similar, with the exception of gender, for which there was a significantly higher proportion of males in the comparator group (26.7% vs 15.2%; p=<0.001). The proportion of enrollees with pneumonia also differed significantly between groups, favoring the comparator group (25% vs 18.4%; p=<0.001). Urinary tract infection proportion favored the GLP-1 RA use cohort (52.7% vs 42.4%; p=<0.01). Additionally, enrolled comorbidities varied only in heart failure between the two cohorts (3.2% comparator group vs 1.3% use of GLP-1 RA; p=0.0085). The odds ratio (OR) for sepsis was 1.17 [95% CI: 0.85-1.46] (p=0.789) and the OR for severe sepsis was 0.92 [95% CI: 0.37-1.63] (p=0.934), indicating that the occurrence of sepsis and severe sepsis did not differ significantly between the two groups after controlling for baseline confounders.

Conclusions:
GLP-1 RA use was not associated with any significant difference in the odds of sepsis, nor of severe sepsis, in acutely ill enrollees with concurrent infection. GLP-1 RA combination products with dual mechanisms were examined alongside sole GLP-1 RA use. Differences in therapy were not examined.  Overall, the evidence is not sufficient to conclude that there is a difference in sepsis risk with GLP-1 RA use.