Abstract
BACKGROUND: Systemic inflammation plays a critical role in the development of obesity-related complications, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for glycemic control and weight management, with emerging evidence suggesting potential anti-inflammatory effects. OBJECTIVE: To examine the association between GLP-1RA use and systemic inflammation, measured by high-sensitivity C-reactive protein (hs-CRP), in a nationally representative sample of U.S. adults. METHODS: We conducted a cross-sectional analysis using National Health and Nutrition Examination Survey (NHANES) 2005-2010 data. Survey-weighted linear regression models were used to assess the relationship between GLP-1 use and log-transformed CRP, adjusting for demographic, socioeconomic, and clinical factors. RESULTS: GLP-1 users had significantly higher CRP levels in unadjusted models (β=1.081, p<0.01). However, after adjusting for age, gender, race/ethnicity, income, body mass index (BMI), diabetes, glycated hemoglobin (HbA1c), and smoking, the association was no longer statistically significant (β=0.323, p=0.38). Clinical factors accounted for most of the variance. CONCLUSION: In this cross-sectional, population-based analysis, GLP-1RA use was not independently associated with lower systemic inflammation after accounting for demographic and clinical confounders. The higher hs-CRP observed among GLP-1 users in unadjusted models is most consistent with confounding by indication and greater cardiometabolic disease burden among treated individuals rather than a direct pro-inflammatory effect of the medications. Longitudinal studies with larger contemporary samples (including newer GLP-1 agents) and repeated inflammatory measures are needed to clarify whether GLP-1 therapies exert direct anti-inflammatory effects beyond their metabolic benefits.