Benfluorex was withdrawn from European markets in June 2010 following reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least three months and in diabetic controls never exposed to the drug.

This reader-blinded controlled study conducted in ten centres in France included prospectively between November 2009 and September 2011 393 consecutive diabetic subjects previously exposed to benfluorex referred by primary care physicians for echocardiography screening and 393 diabetic controls. Using propensity scores, 303 patients and 303 controls were matched for age, gender, body mass index, smoking, dyslipidemia, hypertension, coronary artery disease, and previous use of other drugs associated with valve lesions. The main outcome measure was the frequency of mild or greater left heart valve regurgitations.

In the matched sample, the frequency and relative risk (OR) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared to controls: 30·0% vs. 13·5% (OR 2.96[1·94-4·53]) for aortic and/or mitral regurgitation; 21·1% vs. 5·0% (OR 5·63[3·08-10·3]) for aortic regurgitation, and 17·2% vs. 10·2% (OR 1·99[1·22-3·25]) for mitral regurgitation. The frequency of moderate left heart valve regurgitations was also increased among benfluorex patients vs. controls (7·3% vs. 0·7%; OR 13·9[3·21-60·7].

Our results indicate that use of benfluorex is associated with significant increase in the frequency of left heart valve regurgitations. The natural history of benfluorex-induced valve abnormalities needs further research.