Clinical trial NCT05500937: Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin
Official title: Effect of UDCA on the New Onset Diabetes and Glucose Intolerance Induced by Statin-A Multicenter, Prospective, Random Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Diabetes Mellitus
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
First posted: 2022-08-15
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: At present, it is recognized that statins are the cornerstone of treatment for the prevention of major cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD); However, at the same time, the increased risk of long-term glucose tolerance and type 2 diabetes mellitus caused by statin therapy has attracted wide attention. The investigators' recent study found that the levels of glycosylated hemoglobin, insulin and C-peptide increased significantly with the extension of follow-up time in patients with hyperlipidemia. At the same time, serum and fecal bile acid metabolism profiles, especially secondary bile acid metabolism, were extensively changed, especially in ursodeoxycholic acid (UDCA), suggesting that the decrease of UDCA is a possible mechanism for statins to induce side effects of diabetes. According to this hypothesis, ursodeoxycholic acid combined with statins may improve the abnormal glucose tolerance caused by statins and maximize the benefit of statins. This study is a multicenter, prospective, randomized, parallel, double-blind placebo-controlled, cohort study. Taking ASCVD patients as the research object, the investigators will compare the changes of glycosylated hemoglobin, fasting blood glucose, fasting insulin, C-peptide and metabolomic indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone and during follow-up, Further evaluate the changes of blood glucose related indexes before and after the use of ursodeoxycholic acid combined with atorvastatin and atorvastatin alone, clarify the possible mechanism and specific treatment targets of abnormal glucose tolerance caused by statin, and put forward a possible alternative treatment for the disorder of glucose metabolism caused by statin.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old and \< 80 years old, regardless of gender;
* For those who had indications for taking statins for more than half a year, glycosylated hemoglobin increased by more than 0.5 and \> 6.1% compared with half a year ago;
* Agree to accept the study treatment plan and voluntarily sign the informed consent form.

Exclusion Criteria:

* previous diagnosis of diabetes mellitus;
* Received hypoglycemic drug treatment;
* The level of abdominal blood glucose at baseline was ≥ 7mmol / L;
* Need to take glucocorticoids for a long time;
* Acute myocardial infarction and stroke occurred in the last 6 months;
* Severe liver dysfunction;
* Glomerular filtration rate (EGFR) \< 30ml / min / 1.73m2 (MDRD formula);
* Malignant tumor;
* Blood system diseases;
* Acute or severe systemic infection;
* Women during pregnancy, lactation and preparation for pregnancy;
* Alcohol and other drug addicts and mental patients;
* Patients who are participating in other clinical studies or withdraw from less than 1 month;

Primary outcomes:
measure: Changes of HbA1c
timeFrame: 12 months after enrollment
Secondary outcomes:
measure: Concentration of blood lipid
timeFrame: 12 months after enrollment
measure: Concentration of fasting blood glucose
timeFrame: 12 months after enrollment
measure: Concentration of fasting islets
timeFrame: 12 months after enrollment
measure: Concentration of bile acids
timeFrame: 12 months after enrollment
measure: Rate of MACE
timeFrame: 12 months after enrollment
Other outcomes:
Locations:
city: Xi'an
country: China
facility: First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Zuyi Yuan
role: STUDY_CHAIR
References: