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Diabetes and Metabolism Research Group, Centre hospitalier universitaire de Sherbrooke, Sherbrooke, Que.
[Two of the authors respond:]
Eddie Vos questions the use of fibrates for patients with type 2 diabetes mellitus. In our trial,1 9 patients were given fibrates, in accordance with recommendations of the Canadian Diabetes Association (CDA).
Use of statins or fibrates has been the subject of debate for some time. Statin trials in patients with diabetes have provided convincing evidence of a substantial benefit stemming from this class of drugs. Trials have been conducted with gemfibrozil,2,3 bezafibrate,4 clofibrate5 and fenofibrate.6 Some of these had positive results in terms of primary prevention (Helsinki Heart Study2 and a World Health Organization study5) and secondary prevention (Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial [VA-HIT]3). However, the results of the Bezafibrate Infarction Prevention (BIP) trial4 and the FIELD trial6 were mixed: positive outcomes were observed only in certain subgroups, raising reservations related to an increase in noncardiovascular mortality. Reasons for the differences in outcomes were not immediately apparent.
It emerged in post hoc subgroup analyses of data from the Helsinki Heart Study,7 the VA-HIT8 and the BIP study9 that fibrate-induced reductions in cardiovascular events were especially pronounced (on the order of 30%–50%) in subjects with evidence of insulin resistance or other features of metabolic syndrome, such as dyslipidemia and increased body weight, or in people with both diabetes and preexisting cardiovascular disease. These results were not found in the FIELD study.
The observation that the cardioprotective effects of gemfibrozil were substantially greater than those of other fibrates may be no more than fortuitous or may reflect differences in the populations studied. However, it is also possible that gemfibrozil has either protective properties that are lacking in other fibrates, or that other fibrates have adverse properties not shared by gemfibrozil.
Accordingly, the debate continues, more research is needed, and whether or not diabetes associations will alter their clinical recommendations is an open question. At present, the FIELD study has introduced doubts but not enough evidence to change the current guidelines.
REFERENCES
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Copyright 1995-2006, Canadian Medical Association. All rights reserved. ISSN 1488-2329
(e) 0820-3946 (p)
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association. |
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