Home  |  About JAPTR |  Editorial board  |  Search |  Ahead of print  |  Current issue  |  Archives |  Submit article  |  Instructions  |  Subscribe  |  Advertise  |  Contacts  |Login 
Users Online: 361   Home Print this page Email this page Small font sizeDefault font sizeIncrease font size
     

 Table of Contents  
ORIGINAL ARTICLE
Year : 2018  |  Volume : 9  |  Issue : 4  |  Page : 135-138  

Comparative study of the effect of atorvastatin and fenofibrate on high-density lipoprotein cholesterol levels in patients with type 2 diabetes


1 Young Researchers and Elite Club, Ardabil Branch, Islamic Azad University; Department of Endocrinology, Faculty of Medicine, Azad Ardabil University of Medical Sciences, Ardabil, Iran
2 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Date of Web Publication10-Dec-2018

Correspondence Address:
Dr. Farzad Najafipour
Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz
Iran
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/japtr.JAPTR_314_18

Rights and Permissions
  Abstract 


Diabetes is the most common metabolic disease. Type 2 diabetes is a variable combination of insulin resistance and disorder in insulin secretion, leading to disorder of lipids and plasma lipoproteins. The most common pattern of dyslipidemia in diabetic is high triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C). This study was conducted to find a more effective drug to increase HDL-C. In this study, 80 patients (26 males and 54 females) with type 2 diabetes received fenofibrate in cross-sectional way for 2 months, and they did not take antilipid drugs for 2 month. Then, they underwent atorvastatin for 2 months and HDL-C was measured before and after taking drugs. Patients did not change their diet during this study. Effect of atorvastatin and fenofibrate on HDL-C levels in patients with type 2 diabetes was evaluated. The mean HDL-C and total cholesterol (TC) before and after taking drugs were 36.5 mg/dL and 174.56 mg/dL, respectively. After atorvastatin, the mean HDL-C and TC were 43.30 and 150.144 mg/dL, respectively, and after fenofibrate, 43.40 were mg/dL and 146.36 mg/dL, respectively. Atorvastatin caused increase in HDL-C by 18.44% and reduction in TC by 13.82% and fenofibrate increase in HDL-C by18.62% and reduction in TC by 16.05%. No difference was seen between atorvastatin and fenofibrate in terms of effect on the HDL-C excess (P = 0.449). In addition, no difference was seen between atorvastatin and fenofibrate in terms of effect on TC reduction (P = 0.992). In conclusion various factors are involved in increasing the HDL, such as race, sex, nutrition, physical activity and, of course, medications. The effect of medications is also different on races and genetics. The value of increase in HDL-C after Fenofibrate and Atorvastatin was associated with gender so that it caused more increase of HDL-C in females.

Keywords: Atorvastatin, fenofibrate, high-density lipoprotein cholesterol, type 2 diabetes


How to cite this article:
Najafipour M, Zareizadeh M, Khokhi MA, Najafipour F. Comparative study of the effect of atorvastatin and fenofibrate on high-density lipoprotein cholesterol levels in patients with type 2 diabetes. J Adv Pharm Technol Res 2018;9:135-8

How to cite this URL:
Najafipour M, Zareizadeh M, Khokhi MA, Najafipour F. Comparative study of the effect of atorvastatin and fenofibrate on high-density lipoprotein cholesterol levels in patients with type 2 diabetes. J Adv Pharm Technol Res [serial online] 2018 [cited 2019 Sep 15];9:135-8. Available from: http://www.japtr.org/text.asp?2018/9/4/135/247172




  Introduction Top


Type 2 diabetes is the most common type of diabetes.[1] Cardiovascular disease is one of the macrovascular complications of diabetes and is very common in type 2 diabetic patients. It is also the most common cause of death in these patients.[2],[3] One of the cardiovascular risk factors in diabetic patients is dyslipidemia. The most common form of dyslipidemia in diabetic patients is an increase in triglyceride (TG) and reduction in high-density lipoprotein cholesterol (HDL-C).[4],[5] HDL-C is a lipoprotein with high density, and unlike other atherogenic lipoproteins, HDL-C has anti-atherogenic properties and plays a protective role in cardiovascular disease.[6],[7]

HDL-C takes the cholesterol from foam cells in atherosclerotic lesions and protects low-density lipoprotein-cholesterol (LDL-C) against oxidative changes.[6] Atorvastatin is a lipid-lowering agent from β-Hydroxy β-methyl glutaryl-CoA inhibitors group. This drug with its usual dose reduces total cholesterol (TC) level by 20%–30%, reduces LDL-C level by 21%–60%, and reduces TG level by 7%–37% and increases HDL-C level by about 5%–10%.[7],[8] Fenofibrate is a lipid-lowering drug of fibrates group. This group of drugs reduces very LDL-C through environmental effects.[9],[10] Treatment with this drug reduces TG level by 30%–50% and increases serum HDL-C level by about 5%–15%.[11] However, it cannot reduce the LDL-C level as much as statins; however, it can be useful in diabetic patients because it transforms high-atherogenic LDL-C particles into floating particles, which have less atherogenic properties.[12],[13] As reducing serum HDL-C level is one of the risk factors for cardiovascular diseases, to increase serum level of HDL-C, in addition to dietary measures, stop of smoking, exercise, and blood glucose control, drug therapy also seems to be essential.[6],[14] This study was conducted to determine a more effective drug for increasing serum HDL-C levels.


  Methodology Top


This study was a prospective, clinical cross-sectional study. The study population included 80 patients with type 2 diabetes. This study compared the effect of atorvastatin and fenofibrate on HDL-C level. HDL-C and TC levels were measured before and after the study and fenofibrate was prescribed to these patients for 2 months and HDL-C and TC levels were measured. Anti-lipid drug was not used for 1 month. Atorvastatin was started for patients for 2 months and HDL-C and TC were measured. The obtained data were analyzed using IBM SPSS Statistics for Windows, Version 21 (IBM Corp., Armonk, NY: USA) statistical tests of paired t-test ANOVA and t-test. The significance level in this study was considered P < 0.05.


  Results Top


The subjects were 80 patients (32.5% male and 67.5% female). The mean HDL-C and TC are shown in [Table 1].
Table 1: Levels of high-density lipoprotein cholesterol and total cholesterol before and after antilipid therapy

Click here to view


The mean serum HDL-C levels before and after fenofibrate and atorvastatin are shown in [Table 2] (P = 0.035).
Table 2: Levels of high-density lipoprotein cholesterol in male and female before and after antilipid therapy

Click here to view


Generally, without considering the gender, atorvastatin and fenofibrate did not differ significantly in reducing TC (P = 0.99) and increasing the serum of HDL-C (P = 0.449). Mean TC after fenofibrate was 146.3 mg/dL and after taking fenofibrate was 147.1 mg/dL in males and 147.3 mg/dL in females. The TC level did not show a significant relationship with gender after taking fenofibrate. Atorvastatin increased HDL-C level by 18.54% and decreased TC level by 13.82%. Atorvastatin increased serum HDL-C by 12.2% in males and 21% in females. Fenofibrate increased serum HDL-C level by 14% in males and 20% in females.

The mean fasting blood glucose (FBS) before and after treatment was 105 mg/dL and 110 mg/dL, respectively, and the mean glycated hemoglobin (HbA1c) before and after treatment was 6.5% and 6.7%, respectively. The mean TG before and after treatment with fenofibrate was 215 and 180 mg/dL, respectively, and before and after treatment with atorvastatin was 195 and 205 mg/dL, respectively.


  Discussion Top


The effect of the medicine cannot be limited to studies in other countries.[15],[16] Various factors are involved in increasing the HDL, such as race, sex, nutrition, physical activity, and of course, medications.[16] The effect of medications is also different on races and genetics.[17],[18] Today, in modern therapy, the patient's genetic predisposition is determined for the best medicine.[19],[20] Genetic variants can effect drug metabolism, drug transport, or drug targets.[21],[22] Genetic variation likely contributes substantially to the variation in drug response observed across human populations.[23] The field of pharmacogenomics, which seeks to relate genetic variability to variability in human drug response, has evolved considerably from candidate gene studies to studies of variation across whole genomes of human populations containing individuals who exhibit a range of responses to different drugs.[24],[25] The present study compared the effect of atorvastatin and fenofibrate on the increase of serum HDL-C in 80 diabetic patients. This study is important for two reasons. First, all intervening factors were completely eliminated, and second, atorvastatin and fenofibrate were prescribed only to increase HDL-C and other indices such as TG, TC, FBS, and HbA1c were normal. This study showed that atorvastatin increased the serum HDL-C by 18.54% and decreased the TC by 13.82%. However, in other studies, atorvastatin increased serum HDL-C level by 5%–10% and reduced TC by 20%–30%. However, in some studies, the level of TC decreased by 40% and level of HDL-C increased by 5%–10%.[14] No study has used atorvastatin as the first line of treatment to increase HDL-C, but proper blood glucose control and use of fibrates have been used as the first line of treatment to increase HDL-C.[4],[9],[26] The important result of this study was a significant relationship between increase in HDL-C after atorvastatin and gender (P = 0.006), while other studies did not examine the relationship between gender and the effect of these drugs.[3],[27] In this study, atorvastatin increased HDL-C by 21% in females and by 12.2% in males, reflecting the greater effect of atorvastatin on serum HDL-C in females. In this study, fenofibrate increased serum HDL-C level by 18.54% and decreased the TC by 16.05%. Other studies have reported different level of increase in HDL-C (6%–19%, 10%–25%–10%–15%).[27],[28] The level of reduction in TC was also reported 10%.[12],[29],[30] The increase in serum HDL-C level in this study was consistent with results of previous studies, but the effect of fenofibrate on TC was higher than that of previous studies. It could be due to the low sample size, specific conditions of patients, and the difference in the duration of treatment. In this study, a significant correlation was found between serum HDL-C levels after fenofibrate and gender (P = 0.035). Thus, fenofibrate increased serum HDL-C levels by 14% in males and by 20% in females. In this study, unlike previous studies, no difference was found between atorvastatin and fenofibrate in terms of their effect on HDL-C (P = 0.449). Atorvastatin and fenofibrate also did not differ significantly in terms of effect on TC (P = 0.099). Considering the significant relationship between gender and atorvastatin and fenofibrate, more extensive studies are needed in this regard and conducting more extensive studies is recommended to determine the effect of these drugs on Iranian patients.


  Conclusion Top


Various factors are involved in increasing the HDL, such as race, sex, nutrition, physical activity, and of course, medications. The effect of medications is also different on races and genetics. The value of increase in HDL-C after Fenofibrate and Atorvastatin was associated with gender so that it caused more increase of HDL-C in females.

Acknowledgments

This study was financially supported by Tabriz University of Medical Sciences.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Chan DC, Watts GF, Ooi EM, Ji J, Johnson AG, Barrett PH, et al. Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008;28:1831-7.  Back to cited text no. 1
    
2.
Davidson MH, Rooney MW, Drucker J, Eugene Griffin H, Oosman S, Beckert M, et al. Efficacy and tolerability of atorvastatin/fenofibrate fixed-dose combination tablet compared with atorvastatin and fenofibrate monotherapies in patients with dyslipidemia: A 12-week, multicenter, double-blind, randomized, parallel-group study. Clin Ther 2009;31:2824-38.  Back to cited text no. 2
    
3.
Najafipour M, Khalaj MR, Zareizadeh M, Najafipour F. Relationship between high-sensitivity C-reactive protein and components of metabolic syndrome. J Res Med Dent Sci 2018;6:7-11.  Back to cited text no. 3
    
4.
van der Hoogt CC, de Haan W, Westerterp M, Hoekstra M, Dallinga-Thie GM, Romijn JA, et al. Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression. J Lipid Res 2007;48:1763-71.  Back to cited text no. 4
    
5.
Vosoughi A, Aliasgarzadeh A, Bahrami A, Abbasalizadeh F, Niafar M, Najafipour F, et al. Concentration of maternal serum 25-Hydroxy vitamin D and gestational 2 Diabetes mellitus risk: 25-Hydroxyvitamin D concentrations and gestational diabetes mellitus. PHARM 2017;23:189-92.  Back to cited text no. 5
    
6.
Aghamohammadzadeh N, Niafar M, Dalir Abdolahinia E, Najafipour F, Mohamadzadeh Gharebaghi S, Adabi K, et al. The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients. Ther Adv Endocrinol Metab 2015;6:56-60.  Back to cited text no. 6
    
7.
Najafipour M, Zareizadeh M, Najafipour F. Prevalence of DM, IFG and IGT in thalassemia major in Tabriz. Asian J Pharm 2018;12:S615.  Back to cited text no. 7
    
8.
Arca M, Montali A, Pigna G, Antonini R, Antonini TM, Luigi P, et al. Comparison of atorvastatin vs. fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia. Metabolism 2007;56:1534-41.  Back to cited text no. 8
    
9.
Aghamohammadzadeh N, Aliasgarzadeh A, Baglar L, Abdollahifard S, Bahrami A, Najafipour F, et al. Comparison of metformin and cyproteroneestrodiol compound effect on hs c-reactive protein and serum androgen levels in patients with poly cystic ovary syndrome. Pak J Med Sci 2010;26:347-51.  Back to cited text no. 9
    
10.
Filippatos T, Milionis HJ. Treatment of hyperlipidaemia with fenofibrate and related fibrates. Expert Opin Investig Drugs 2008;17:1599-614.  Back to cited text no. 10
    
11.
Taskinen MR, Sullivan DR, Ehnholm C, Whiting M, Zannino D, Simes RJ, et al. Relationships of HDL cholesterol, apoA-I, and apoA-II with homocysteine and creatinine in patients with type 2 diabetes treated with fenofibrate. Arterioscler Thromb Vasc Biol 2009;29:950-5.  Back to cited text no. 11
    
12.
Phuntuwate W, Suthisisang C, Koanantakul B, Chaloeiphap P, Mackness B, Mackness M. Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels. Atherosclerosis 2008;196:122-8.  Back to cited text no. 12
    
13.
Aghamohammadzadeh N, Tabrizi A, Niafar M, Najafipor F. Efficacy of adding glutazone to the maximum dose of glibenclamide and metformin resistant on type 2 diabetic patients. Caspian J Int Med 2010;1:9-11.  Back to cited text no. 13
    
14.
Moutzouri E, Kei A, Elisaf MS, Milionis HJ. Management of dyslipidemias with fibrates, alone and in combination with statins: Role of delayed-release fenofibric acid. Vasc Health Risk Manag 2010;6:525-39.  Back to cited text no. 14
    
15.
Weinshilboum RM, Sladek SL. Mercaptopurine pharmacogenetics: Monogenic inheritance of erythrocyte thiopurine methyltransferase activity. Am J Hum Genet 1980;32:651-62.  Back to cited text no. 15
    
16.
Daly AK. Genome-wide association studies in pharmacogenomics. Nat Rev Genet 2010;11:241-6.  Back to cited text no. 16
    
17.
Ramsey LB, Bruun GH, Yang W, Treviño LR, Vattathil S, Scheet P, et al. Rare versus common variants in pharmacogenetics: SLCO1B1 variation and methotrexate disposition. Genome Res 2012;22:1-8.  Back to cited text no. 17
    
18.
Madian AG, Wheeler HE, Jones RB, Dolan ME. Relating human genetic variation to variation in drug responses. Trends in Genetics 2012;28:487-95.  Back to cited text no. 18
    
19.
Pearson TA, Manolio TA. How to interpret a genome-wide association study. JAMA 2008;299:1335-44.  Back to cited text no. 19
    
20.
Wilkening S, Chen B, Bermejo JL, Canzian F. Is there still a need for candidate gene approaches in the era of genome-wide association studies? Genomics 2009;93:415-9.  Back to cited text no. 20
    
21.
Chen SH, Yang W, Fan Y, Stocco G, Crews KR, Yang JJ, et al. A genome-wide approach identifies that the aspartate metabolism pathway contributes to asparaginase sensitivity. Leukemia 2011;25:66-74.  Back to cited text no. 21
    
22.
Wheeler HE, Gamazon ER, Stark AL, O'Donnell PH, Gorsic LK, Huang RS, et al. Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations. Pharmacogenomics J 2013;13:35-43.  Back to cited text no. 22
    
23.
Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, et al. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009;41:816-9.  Back to cited text no. 23
    
24.
Wadelius M, Alfirevic A. Pharmacogenomics and personalized medicine: The plunge into next-generation sequencing. Genome Med 2011;3:78.  Back to cited text no. 24
    
25.
Najafipour M, Zareizadeh M, Najafipour F. Epidemiologic study of familial type 2 diabetes in Tehran. J Adv Pharm Technol Res 2018;9:56-60.  Back to cited text no. 25
[PUBMED]  [Full text]  
26.
Niafar M, Samadi G, Aghamohammadzadeh N, Najafipour F, Nikniaz Z. There is a positive association between vitamin B12 deficiency and serum total cholesterol in Iranian type 2 diabetic patients on Metformin. Nutr Clin Métab 2018; In press.  Back to cited text no. 26
    
27.
Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): Randomised controlled trial. Lancet 2005;366:1849-61.  Back to cited text no. 27
    
28.
Ting RD, Keech AC, Drury PL, Donoghoe MW, Hedley J, Jenkins AJ, et al. Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: The FIELD study. Diabetes Care 2012;35:218-25.  Back to cited text no. 28
    
29.
Franceschini G, Calabresi L, Colombo C, Favari E, Bernini F, Sirtori CR, et al. Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients. Atherosclerosis 2007;195:385-91.  Back to cited text no. 29
    
30.
Parikh RM, Joshi SR, Menon PS, Shah NS. Prevalence and pattern of diabetic dyslipidemia in India type 2 diabetic patients. Diabetes Metab Syndr 2010;4:10-2.  Back to cited text no. 30
    



 
 
    Tables

  [Table 1], [Table 2]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
   Abstract
  Introduction
  Methodology
  Results
  Discussion
  Conclusion
   References
   Article Tables

 Article Access Statistics
    Viewed643    
    Printed20    
    Emailed0    
    PDF Downloaded109    
    Comments [Add]    

Recommend this journal