Multitherapy for diabetes
=========================

* Eddie Vos

Julie Ménard and associates1 used pravastatin or bezafibrate (or both) as a component of intensive multitherapy in their study of patients with type 2 diabetes mellitus. Although pravastatin is of questionable benefit (according to the ALLHAT-LLT study,2 in which no cardiovascular, peripheral vascular, cerebrovascular or mortality benefits were found), my main concern here is with the use of fibrates.

Fibrates, including bezafibrate, are effective in lowering low-density lipoprotein cholesterol and triglycerides while raising high-density lipoprotein cholesterol, but there was no mortality benefit in a large bezafibrate trial.3 In addition, there have now been 3 trials with different fibrates (gemfibrozil,4 clofibrate5 and fenofibrate6) that ended with numerically more deaths in the group receiving fibrates than in the placebo group.

Fibrates lull patients and doctors into a false sense of accomplishment by bringing several blood lipid markers closer to guideline targets, thus reducing the urgency of more difficult dietary and lifestyle changes. However, with “over two-thirds of patients with diabetes [dying] of cardiovascular causes,”7 the established failure of fibrates to lower mortality should lead to an urgent call to stop their use and to examine the clinical efficacy of the lipid guidelines.

## REFERENCES

1.  1. Ménard J, Payette H, Baillargeon JP, et al. Efficacy of intensive multitherapy for patients with type 2 diabetes mellitus: a randomized controlled trial. CMAJ 2005;173(12):1457-66.
    
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2.  2. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA 2002;288:2998-3007.
    
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3.  3. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000;102:21-7.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjg6IjEwMi8xLzIxIjtzOjQ6ImF0b20iO3M6MjQ6Ii9jbWFqLzE3NS8xMC8xMjQ2LjIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

4.  4. Huttunen JK, Heinonen OP, Manninen V, et al. The Helsinki Heart Study: an 8.5-year safety and mortality follow-up. J Intern Med 1994;235:31-9.
    
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5.  5. W.H.O. cooperative trial on primary prevention of ischaemic heart disease using clofibrate to lower serum cholesterol: mortality follow-up. Report of the Committee of Principal Investigators. Lancet 1980;2:379-85.
    
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6.  6. Keech A, Simes RJ, Barter P, 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.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0140-6736(05)67667-2&link_type=DOI) 
    
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7.  7. Rothman RL, Elasy TA. Can diabetes management programs create sustained improvements in disease outcomes? [editorial]. CMAJ 2005;173:1467-8.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMToiMTczLzEyLzE0NjciO3M6NDoiYXRvbSI7czoyNDoiL2NtYWovMTc1LzEwLzEyNDYuMi5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=)