Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus.
<h4>Objectives</h4>REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients.<h4>Methods</h4>Double-blind, parallel-group, international, randomised, non-inferiority trial. More than half of the...
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Public Library of Science (PLoS)
2012-01-01
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| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0038273&type=printable |
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| author | Geneviève Derumeaux Laura Ernande André Serusclat Evelyne Servan Eric Bruckert Hugues Rousset Stephen Senn Luc Van Gaal Brigitte Picandet François Gavini Philippe Moulin REGULATE trial investigators |
| author_facet | Geneviève Derumeaux Laura Ernande André Serusclat Evelyne Servan Eric Bruckert Hugues Rousset Stephen Senn Luc Van Gaal Brigitte Picandet François Gavini Philippe Moulin REGULATE trial investigators |
| author_sort | Geneviève Derumeaux |
| collection | DOAJ |
| description | <h4>Objectives</h4>REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients.<h4>Methods</h4>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.<h4>Results</h4>At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c 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 HbA1c 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.<h4>Conclusion</h4>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. |
| format | Article |
| id | doaj-art-727308f118d2428ca4887c50aa6ecb6f |
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| language | English |
| publishDate | 2012-01-01 |
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| spelling | doaj-art-727308f118d2428ca4887c50aa6ecb6f2025-08-20T02:20:13ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0176e3827310.1371/journal.pone.0038273Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus.Geneviève DerumeauxLaura ErnandeAndré SerusclatEvelyne ServanEric BruckertHugues RoussetStephen SennLuc Van GaalBrigitte PicandetFrançois GaviniPhilippe MoulinREGULATE trial investigators<h4>Objectives</h4>REGULATE trial was designed to compare the efficacy and safety of benfluorex versus pioglitazone in type 2 diabetes mellitus (DM) patients.<h4>Methods</h4>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.<h4>Results</h4>At baseline, patients were 59.1 ± 10.5 years old with HbA1c 8.3 ± 0.8%, and DM duration 7.1 ± 6.0 years. During the study, mean HbA1c 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 HbA1c 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.<h4>Conclusion</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0038273&type=printable |
| spellingShingle | Geneviève Derumeaux Laura Ernande André Serusclat Evelyne Servan Eric Bruckert Hugues Rousset Stephen Senn Luc Van Gaal Brigitte Picandet François Gavini Philippe Moulin REGULATE trial investigators Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. PLoS ONE |
| title | Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. |
| title_full | Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. |
| title_fullStr | Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. |
| title_full_unstemmed | Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. |
| title_short | Echocardiographic evidence for valvular toxicity of benfluorex: a double-blind randomised trial in patients with type 2 diabetes mellitus. |
| title_sort | echocardiographic evidence for valvular toxicity of benfluorex a double blind randomised trial in patients with type 2 diabetes mellitus |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0038273&type=printable |
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