| Title |
|
|
|
Echocardiographic evidence for valvular toxicity of benfluorex : a double-blind randomised trial in patients with type 2 diabetes mellitus
| |
| Author |
|
|
|
| |
| Institution/Organisation |
|
|
|
REGULATE Trial Investigators
| |
| Abstract |
|
|
|
| Objectives: REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients. Methods: Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the 196 participating centres were primary care centres. Patients eligible had type 2 DM uncontrolled on sulfonylurea. 846 were randomised. They received study treatment for 1 year. 423 patients were allocated to benfluorex (150 to 450 mg/day) and 423 were allocated to pioglitazone (30 to 45 mg/day). Primary efficacy criterion was HbA(1c). Safety assessment included blinded echocardiographic evaluation of cardiac and valvular status. Results: 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. | | |
| Language |
|
|
|
English
| |
| Source (journal) |
|
|
|
PLoS ONE | |
| Publication |
|
|
|
2012
| |
| ISSN |
|
|
|
1932-6203
| |
| Volume/pages |
|
|
|
7:6(2012), 12 p.
| |
| Article Reference |
|
|
|
e38273
| |
| ISI |
|
|
|
000305652700013
| |
| Medium |
|
|
|
E-only publicatie
| |
| Full text (Publisher's DOI) |
|
|
| | |
| Full text (open access) |
|
|
| | |
|