Fibrates in the prevention of cardiovascular disease in patients with type 2 diabetes mellitus: meta-analysis of randomised controlled trials

Objective: To assess the impact of lipid lowering treatment with fibrates on cardiovascular endpoints in patients with type 2 diabetes mellitus. Methods: MEDLINE (from inception to November 2005) and the Cochrane Controlled Trials Register (including Issue 3, 2005) were searched for randomised controlled trials comparing therapy with fibrates to placebo in patients with type 2 diabetes mellitus. Electronic searches were supplemented by manual searching of reference lists, reviews, conference abstracts and specialist journals. Incidence rate ratios (IRRs) were estimated using a fixed effects model. The primary endpoint was the IRR for coronary heart disease (CHD) events (a combination of non fatal myocardial infarction and death due to CHD). Secondary endpoints included: (1) death due to CHD; (2) fatal and non fatal myocardial infarction; and (3) fatal and non fatal stroke. Results: Eight trials and 12 249 patients with type 2 diabetes were included in the analyses. A total of 924 CHD events (418 and 506 in the treatment and placebo groups, respectively) occurred during a follow up of 60 395 person-years (30 106 and 30 289 in treatment and placebo groups). The combined IRR for CHD events was 0.84 (95% confidence interval [CI] 0.74-0.96, p = 0.008). The numbers needed to treat (NNTs) to prevent one CHD event over 10 years were nine and 26 for patients with and without pre-existing CHD, respectively. IRRs for death due to CHD, myocardial infarction and stroke were 0.96 ( 95% CI 0.77-1.20, p = 0.73), 0.88 (95% CI 0.69-1.12, p = 0.30) and 0.87 (95% CI 0.73-1.05, p = 0.14), respectively. Larger benefits were found when restricting the analysis to trials that were not confounded by unequal provision of additional lipid-lowering therapy. Conclusions: Fibrates are associated with a substantial reduction of CHD events, but their exact role in lipid lowering treatment of patients with type 2 diabetes mellitus remains to be defined.