Background: Glucagon-like peptide-1 (GLP-1) agonists are increasingly prescribed for obesity and type 2 diabetes, demonstrating efficacy in weight loss and glycemic control [1-3]. Beyond metabolic effects, these medications show protective effects against renal disease progression and reduce major adverse cardiovascular events [4]. GLP-1 agonists influence body composition through effects on both fat mass and fat-free mass [5], which includes skeletal muscle important for metabolic health and physical function. Given that critically ill patients experience severe protein catabolism and up to 43% develop ICU-acquired weakness [6], questions arise about outcomes during critical illness when metabolic demands are high [7]. Despite widespread use, the relationship between prior GLP-1 agonist use and critical care outcomes remains unknown.
Methods: We conducted a retrospective cohort study using data from Stanford Health Care between January 2015 and July 2024. Adults aged 18-89 years admitted to intensive care with BMI 20-60 were included. Of 24,955 eligible ICU patients, the GLP-1 agonist group (n=735, 2.9%) received GLP-1 agonist prescriptions within 12 months before hospitalization; the comparison group did not receive GLP-1 agonists within 12 months before hospitalization. Using high-dimensional propensity score matching with lasso regression, we created 719 matched pairs and compared in-hospital mortality, hospital length of stay, and ICU length of stay between groups. Sensitivity analyses compared unmatched and different matching approaches to assess result robustness.
Results: In matched analyses, baseline characteristics were well-balanced, including age (64.0 vs 63.4 years), BMI (32.4 vs 31.5), and comorbidities such as diabetes (86.4% vs 86.5%), diabetes with complications (62.7% vs 65.4%), heart failure (49.4% vs 50.1%), and renal disease (54.9% vs 54.1%) (Table 1). The matched GLP-1 agonist group and comparison group (Figure 1) showed similar in-hospital mortality (2.8% vs 3.5%, OR 0.79, 95% CI 0.44-1.44, p=0.45), mean hospital length of stay (8.8 ± 17.6 vs 9.2 ± 16.2 days, IRR 0.95, 95% CI 0.78-1.16, p=0.60), and ICU length of stay (3.5 ± 7.4 vs 3.0 ± 5.5 days, IRR 1.16, 95% CI 0.90-1.50, p=0.24). Results remained consistent across sensitivity analyses, though unmatched analysis showed a slightly higher ICU length of stay in the GLP-1 agonist group that was attenuated after matching.
Conclusions: In this first study examining the relationship between prior GLP-1 agonist use and critical care outcomes, we found no significant differences in mortality or length of stay between groups. These findings provide reassurance about GLP-1 agonist use in patients who may later require critical care, despite these medications’ effects on body composition. GLP-1 agonists’ anti-inflammatory properties [8], improved insulin sensitivity [9], and reduced glucose variability [10] may contribute to these findings. Future research should examine longer-term outcomes and incorporate body composition analysis to elucidate whether GLP-1 agonist use modifies recovery from critical illness.
