Benfluorex

General information

Benfluorex, which is structurally related to fenfluramine, was marketed in 1976 and has been used, mainly in France, as an appetite suppressant [ ] and to improve glycemic control and reduce insulin resistance in people with poorly controlled type 2 diabetes [ ], including those with obesity [ ]. However, in 2009 the European Medicines Agency recommended the withdrawal of all medicines containing benfluorex in the European Union, because of the risks of cardiac valve disease (fenfluramine-like cardiovascular adverse effects) [ ], attributed to the metabolite norfenfluramine.

It has been estimated that in France about five million people were exposed to benfluorex [ ]. In one survey the number of deaths attributable to benfluorex in France before its withdrawal was estimated at 500 [ ]. However, a later calculation suggested a higher rate, based four sets of data: (i) the amount of exposure to benfluorex in the French population, derived from sales figures for the period 1976–2009 and from the main characteristics of benfluorex use provided by the French health products safety agency; (ii) the relative risk of hospitalization for valvular insufficiency among exposed compared with unexposed individuals with diabetes, originating from a cohort study based on a French medico-administrative database, with benfluorex exposure assessed in 2006; (iii) the incidence of hospitalization for valvular insufficiency among exposed individuals, originating from the same database; and (iv) the mortality associated with valvular heart disease [ ]. The authors suggested that the use of benfluorex in France during 1976–2009 was likely to have been responsible for about 3100 hospital admissions and 1300 deaths due to valvular insufficiency, and that these figures may even be underestimates.

Organs and systems