Echocardiographic Evidence for Valvular Toxicity of Benfluorex: A Double-Blind Randomised Trial in Patients with Type 2 Diabetes Mellitus
Abstract
At baseline, patients were 59.1+/-10.5 years old with HbA(1c) 8.3+/-0.8%, and DM duration 7.1+/-6.0 years. During the study, mean HbA(1c) significantly decreased in both groups (benfluorex: from 8.30+/-0.80 to 7.77+/-1.31 versus pioglitazone: from 8.30+/-0.80 to 7.45+/-1.30%).
The last HbA(1c) value was significantly lower with pioglitazone than with benfluorex (p<0.001) and non-inferiority of benfluorex was not confirmed (p = 0.19). Among the 615 patients with assessable paired echocardiography (310 benfluorex, 305 pioglitazone), 314 (51%) had at least one morphological valvular abnormality and 515 (84%) at least one functional valvular abnormality at baseline.
Emergent morphological abnormalities occurred in 8 patients with benfluorex versus 4 with pioglitazone (OR 1.99), 95% CI (0.59 to 6.69). Emergent regurgitation (new or increased by one grade or more) occurred more frequently with benfluorex (82 patients, 27%) than with pioglitazone (33 patients, 11%) (OR 2.97), 95% CI (1.91 to 4.63) and were mainly rated grade 1; grade 2 (mild) was detected in 2 patients with benfluorex and 3 with pioglitazone.
There was no moderate or severe regurgitation. Conclusion: After 1 year of exposure, our results show a 2.97 fold increase in the incidence of valvular regurgitation with benfluorex and provide evidence for the valvular toxicity of this drug.