Abstract 16779: Tirzepatide Reduces High-Sensitivity C-reactive Protein in Patients With Type 2 Diabetes and High Cardiovascular Risk: A Post Hoc Analysis of the SURPASS-4 Trial

Abstract

Background: People with type 2 diabetes (T2D) who have elevated levels of high-sensitivity C-reactive protein (hsCRP) face a greater risk of myocardial infarction and coronary death. Early data for tirzepatide (TZP), a GIP/GLP-1 receptor agonist, suggest a hsCRP lowering effect. Here, we compare the effect of TZP and insulin glargine (iGlar) on hsCRP in patients with T2D and established or high risk for cardiovascular (CV) disease. Methods: hsCRP concentration was quantified by immunoassay (Roche, Indianapolis, IN) with lower limits of detection at concentrations of 0.15 mg/L. Plasma was collected from 1995 fasted participants at baseline (329, 328, 338, and 1000 on 5, 10, 15 mg TZP and on iGlar, respectively) and 52 weeks in SURPASS-4. The % changes of hsCRP from baseline were estimated by mixed model with repeated measures. The shifts in hsCRP risk categories (hsCRP >3 mg/L or 1-3 mg/L versus <1 mg/L) from baseline to 52 weeks are reported. The linear relationship between % change from baseline of hsCRP and change in body mass index (BMI) was analyzed using Pearson correlation coefficient. Results: Baseline hsCRP (mean ± SD, 5.6 ± 12.5 mg/L) was elevated in this study population. Among the participants, 48%, 36%, and 16% were in the >3, 1-3 and <1 mg/L hsCRP categories, respectively. Participants in the elevated hsCRP categories had higher body weight and BMI at baseline. After 52 weeks of treatment, the 5, 10, 15 mg TZP and iGlar groups resulted in -38.0%, -44.2%, -47.8%, and 0.6% changes in the concentration of hsCRP, respectively. More TZP-treated patients improved their hsCRP categories when compared with iGlar-treated participants (Table). The reduction in hsCRP in the pooled TZP groups correlated with the reduction of BMI (r=0.07, p=0.049). Conclusions: Tirzepatide treatment significantly lowers hsCRP in patients with T2D and increased CV risk versus baseline and iGlar. Substantially more participants shift to a lower hsCRP category when compared with insulin glargine.