Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Diabetes Mellitus Clinical Trial

Official title:

Effect of Pravastatin in the Subjects With Prediabetes or Early Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02754739
• Other study ID #: 2012-12-103
• Status: Completed
• Phase: Phase 4
• Start date: April 15, 2014
• Est. completion date: August 31, 2017

Study information

• Verified date: September 2018
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: August 31, 2017
• Est. primary completion date: August 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Prediabetic State

Intervention

Drug:
• Pravastatin
Pravastatin 40mg once daily for 24 weeks and nutritional education by a nutritionist
• Placebo (for Pravastatin)
Pill manufactured to mimic pravastatin 40mg tablet once daily for 24 weeks and nutritional education by a nutritionist

Behavioral:
• Nutritional education only
Only nutritional education by a nutritionist

Locations

Country	Name	City	State
Korea, Republic of	Division of Endocrinology and Metabolism, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Samsung Medical Center	Daiichi Sankyo Korea Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (8)

Freeman DJ, Norrie J, Sattar N, Neely RD, Cobbe SM, Ford I, Isles C, Lorimer AR, Macfarlane PW, McKillop JH, Packard CJ, Shepherd J, Gaw A. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001 Jan 23;103(3):357-62. — View Citation

Güçlü F, Ozmen B, Hekimsoy Z, Kirmaz C. Effects of a statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome. Biomed Pharmacother. 2004 Dec;58(10):614-8. — View Citation

Katz A, Nambi SS, Mather K, Baron AD, Follmann DA, Sullivan G, Quon MJ. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000 Jul;85(7):2402-10. — View Citation

Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care. 1999 Sep;22(9):1462-70. — View Citation

Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009 Oct;32(10):1924-9. doi: 10.2337/dc09-0738. — View Citation

Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010 Feb 27;375(9716):735-42. doi: 10.1016/S0140-6736(09)61965-6. Epub 2010 Feb 16. — View Citation

Seltzer HS, Allen EW, Herron AL Jr, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest. 1967 Mar;46(3):323-35. — View Citation

Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, Leonetti DL, McNeely MJ, Fujimoto WY, Kahn SE. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009 Feb;32(2):335-41. doi: 10.2337/dc08-1478. Epub 2008 Oct 28. Erratum in: Diabetes Care. 2009 Jul;32(7):1355. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin resistance assessed by HOMA-IR (homeostatic model assessment index for insulin resistance)	compared to the HOMA-IR level calculated at the initial visit (at the beginning of the 24 weeks of medication period)	at the end of the 24 weeks of medication period
Secondary	Insulin resistance assessed by Matsuda index calculated through 75g oral glucose tolerance test	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	at the end of the 24 weeks of medication period
Secondary	Insulin secretion capacity assessed by insulinogenic index (INS index) during 75g oral glucose tolerance test	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)	at the end of the 24 weeks of medication period
Secondary	Insulin resistance assessed by the quantitative insulin sensitivity check index (QUICKI)	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)	at the end of the 24 weeks of medication period
Secondary	Insulin secretory capacity relative to insulin resistance assessed by the oral disposition index	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)	at the end of the 24 weeks of medication period
Secondary	Glycemic control evaluated by fasting glucose level (mg/dL)	compared to the values at the initial visit	at the end of the 24 weeks of medication period
Secondary	Glycemic control evaluated by hemoglobin A1C (%)	compared to the values at the initial visit	at the end of the 24 weeks of medication period
Secondary	Plasma adioponectin level (µg/ml), an adipocyte-derived insulin-sensitizing hormone level	compared to the values at the initial visit	at the end of the 24 weeks of medication period
Secondary	Biomarkers predicting cardiovascular diseases, assessed by high sensitive C-reactive protein (hsCRP) (mg/dL)	compared to the values at the initial visit	at the end of the 24 weeks of medication period
Secondary	Biomarkers predicting cardiovascular diseases, assessed by plasminogen activator inhibitor-1 (PAI-1) (ng/mL)	compared to the values at the initial visit	at the end of the 24 weeks of medication period