Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Phase 4

Completed

• Conditions: Prediabetic State; Diabetes Mellitus
• Interventions: Behavioral: Nutritional education only; Drug: Placebo (for Pravastatin); Drug: Pravastatin

• Registration Number: NCT02754739
• Lead Sponsor: Samsung Medical Center

Brief Summary

An increased risk of incident diabetes with statin therapy have been reported in several studies. However, it is not recommended to limit the use of statin for this reason since the absolute risk increase was small, and the cardiovascular event rate reduction with statins overweighed the risk of new diabetes (Scatter N et al. Lancet, 2010). Moreover, each statin may have different effect on the development of incident diabetes. In the West of Scotland Coronary Prevention Study, pravastatin therapy reduced the hazard of becoming diabetic by 30%. Also, with pravastatin use, an increase in adiponectin level, which is related to the improvement in insulin sensitivity, has been reported. In this clinical trial, the investigators are aiming to evaluate the effect of pravastatin on insulin resistance, insulin secretion, glycemic control, and adiponectin level in participants with prediabetes or early diabetes by assigning them in a 24 weeks of pravastatin therapy group or in a placebo group.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-15
• Study First Submitted: 2016-04-09
• Study First Submitted QC: 2016-04-25
• Study First Posted: 2016-04-28
• Primary Completion: 2017-08-31
• Study Completion: 2017-08-31
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-11
• Last Update Posted: 2018-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

• Subjects have early diabetes mellitus or prediabetes. Early diabetes mellitus or prediabetes are defined according to the following criteria; Subjects have two or more of the following three, or they have one of them at the initial test and the repeat test.

  1. hemoglobin A1C 5.7-9.0%
  2. fasting plasma glucose level 100mg/dL or more
  3. plasma glucose level 140mg/dL or more at 2 hours after 75g oral glucose tolerance test

• Subjects have one of the following three;

  1. Low-density lipoprotein cholesterol (LDL-cholesterol) 130mg/dL or more, and body mass index (BMI) > 23 kg/m2,
  2. 10 year atherosclerotic cardiovascular disease (ASCVD) risk of 7.5% or more, which is assessed by the ASCVD-Risk-Estimator (Circulation.2014;129:S1-S45)
  3. In diabetic patients, LDL-cholesterol 100mg/dL or more

Exclusion Criteria

• Hemoglobin A1C > 9.0%
• History of statin use in three months
• Use of oral antidiabetic drugs except for metformin in three months
• History of malignant diseases (cancers)
• History of coronary artery diseases, heart failure, arrhythmia, valvular heart diseases, or cerebrovascular diseases
• Pregnant
• serum creatinine level > 1.5 mg/dL
• aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels higher than 80 U/l
• Taking weight loss medications, corticosteroids, Angiotensin converting enzyme (ACE) inhibitors, or estrogen replacement therapy
• Chronic hepatitis B or chronic hepatitis C

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Open-label control	Nutritional education only	No medication. Only nutritional education was provided to participants by a nutritionist, and participants were instructed to follow the educated guideline.
Placebo	Placebo (for Pravastatin)	Placebo drug indistiguishable from pravastatin 40mg tablet, by mouth, once daily for 24 weeks. Also, nutritional education was provided to participants in all arms by a nutritionist, and participants were instructed to follow the educated guideline.
Pravastatin	Pravastatin	Pravastatin 40mg tablet by mouth, once daily for 24 weeks. Also, nutritional education was provided to participants in all arms by a nutritionist, and participants were instructed to follow the educated guideline.

Primary Outcome Measures

Name	Time	Method
Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance)	at the end of the 24 weeks of medication period	compared to the HOMA-IR level calculated at the initial visit (at the beginning of the 24 weeks of medication period)

Secondary Outcome Measures

Name	Time	Method
Insulin secretion capacity assessed by insulinogenic index (INS index) during 75g oral glucose tolerance test	at the end of the 24 weeks of medication period	the ratio relating enhancement of circulating insulin in 30min \[in pmol/L\] to magnitude of corresponding glycemic stimulus in 30min \[in mmol/L\] during the oral glucose tolerance test (H.S. Seltze et al. J. Clin. Investig., 1967), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)
Insulin resistance assessed by the quantitative insulin sensitivity check index (QUICKI)	at the end of the 24 weeks of medication period	calculated using fasting insulin in uIU/mL and fasting plasma glucose in mg/dL according to the method described in a previous study (A. Katz et al. J. Clin. Endocrinol. Metab., 2000), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)
Insulin secretory capacity relative to insulin resistance assessed by the oral disposition index	at the end of the 24 weeks of medication period	calculated according to a method described in a previous study (K.M. Utzschneider et al.Diabetes Care, 2008), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period)
Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL)	at the end of the 24 weeks of medication period	compared to the values at the initial visit
Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL)	at the end of the 24 weeks of medication period	compared to the values at the initial visit
Insulin resistance assessed by Matsuda index calculated through 75g oral glucose tolerance test	at the end of the 24 weeks of medication period	calculated according to a method described in a previous study (Matsuda M et al. Diabetes Care, 1999), compared to the results at the initial visit (at the beginning of the 24 weeks of medication period). It takes 120 minutes to perform 75g oral glucose tolerance test
Plasma adioponectin level (μg/ml), an adipocyte-derived insulin-sensitizing hormone level	at the end of the 24 weeks of medication period	compared to the values at the initial visit
Glycemic control evaluated by fasting glucose level (mg/dL)	at the end of the 24 weeks of medication period	compared to the values at the initial visit
Glycemic control evaluated by hemoglobin A1C (%)	at the end of the 24 weeks of medication period	compared to the values at the initial visit

Trial Locations

Locations (1)

Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine; 🇰🇷 Seoul, Korea, Republic of