Effects of ursodeoxycholic acid on statin-induced impaired glucose tolerance: study protocol for a randomized controlled trial

INTRODUCTION: Statin therapy is associated with an increased risk of dysglycaemia and new-onset type 2 diabetes, which compromises patient adherence. Ursodeoxycholic acid (UDCA), a hepatoprotective drug, has shown potential for improving glycaemic control, but its role in preventing statin-induced dysglycaemia remains unexplored in prospective randomised trials, particularly in a primary prevention setting. This trial aims to determine whether UDCA coadministration can prevent statin-induced impairment of glucose tolerance. METHODS AND ANALYSIS: This is an investigator-initiated, prospective, double-blind, randomised, placebo-controlled trial. A total of 128 participants with newly diagnosed hyperlipidaemia and no history of diabetes or cardiovascular events will be enrolled. Participants will be randomly assigned (1:1) to receive either atorvastatin (20 mg/day) plus UDCA (500 mg/day) or atorvastatin plus a matching placebo for 180 days. The primary outcome is the difference in glycated haemoglobin (HbA1c) absolute change from baseline to Day 180 between the intervention and control groups. The secondary outcomes are the difference in the absolute change of cardiometabolic risk factors and body composition between the intervention and control groups from baseline to Day 180. Safety outcomes include adverse events, serious adverse events, abnormal vital signs and abnormal laboratory parameters from baseline to Day 180. Data will be analysed according to the ITT principle. ETHICS AND DISSEMINATION: This study has been approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (No. XJTU1AF2023LSK-149-02). The study findings will be disseminated through peer-reviewed journals, symposiums and conference presentations. TRIAL REGISTRATION NUMBER: NCT06684106.