A 24-Week, Multi-Center, Randomized, Open-Label Clinical Trial Comparing the Effects of Xuezhikang and Atorvastatin on Glucose Metabolism in Patients with Dyslipidemia and Prediabetes (XTREME Study): Design of the Study Protocol

Background: Statins, a first-line therapeutic option for atherosclerotic cardiovascular disease (ASCVD), have prompted concerns regarding dysglycemia and diabetes, thus posing a dilemma in treating patients with prediabetes. Xuezhikang (XZK) decreases blood cholesterol levels without affecting glucose metabolism, and may serve as a potential substitute. Methods: The XTREME study is a prospective, randomized, open-label, multi-center trial evaluating whether XZK 1200 mg/d, compared with atorvastatin 20 mg/d, has favorable effects on HbA1c levels after 24 weeks of treatment in patients with dyslipidemia and prediabetes. After a 1-week run-in period for adherence assessment, the study will randomly assign (1:1) 392 patients meeting the protocol inclusion criteria to one of two treatment groups: an experimental group (XZK 1200 mg/day) or a control group (atorvastatin 20 mg/day). All participants will be recruited from approximately 20 Chinese medical centers. The last participant is planned to be recruited before December 2023. The primary endpoint will be change in HbA1c level from baseline to 24 weeks, or before anti-diabetic therapy initiation within 24 weeks. The key secondary outcomes will include other biomarkers reflecting blood glucose or lipid metabolism. Discussion: Delaying diabetes is desirable for individuals with prediabetes. The XTREME trial presents a unique opportunity to demonstrate whether XZK might provide an alternative to statins for patients with dyslipidemia and prediabetes.