It was on the market between 1976 and 2009, and is thought to have caused between 500 and 2,000 deaths.[5] It was patented and manufactured by the French pharmaceutical companyServier. However, Servier is suspected of having marketed benfluorex at odds with the drug's medical properties.[6] In fact, Benfluorex acts as a prodrug toNorfenfluramine, a worldwide withdrawnAnorectic because of its high incidence ofCardiac fibrosis[2] which is completely out of line for treatingType 2 diabetes
In 2023, a French court finedServier €415m on appeal after finding it guilty of deception and manslaughter, as Benfluorex's mechanism of action was fraudulently concealed, as Benfluorex was marketed after withdrawal of the any marketedFenfluramine anorectic (Fenfluramine/phentermine,Dexfenfluramine,Clobenzorex,Mefenorex, etc) because of their serious side effects likeCardiac fibrosis andPulmonary hypertension (Benfluorex also shares the same side effects, but they were completely concealed, even though there was several reports ofHeart failure).[7]
On 18 December 2009, theEuropean Medicines Agency recommended the withdrawal of all medicines containing benfluorex in theEuropean Union, because their risks, particularly the risk ofheart valve disease (fenfluramine-like cardiovascular side effects), are greater than their benefits.[8] Thus Frachonet al. showed a higher rate of unexplained valvular heart disease in people taking benfluorex.[2] Weillet al. looked at over 1 million people with diabetes demonstrating a higher hospitalization rate in benfluorex takers for valvular heart disease.[9]In France, the medication had been marketed by Servier as an adjuvantantidiabetic under the name Mediator. The drug was on the market between 1976 and 2009, and is thought to have caused between 500 and 2,000 deaths.[5] The drug was also used in Spain, Portugal, and Cyprus.
On March 29, 2021, a French court fined Servier €2.7m (£2.3m) after finding it guilty of deception and manslaughter, with Mediator linked to the deaths of up to 2,000 people. The former executive Jean-Philippe Seta was sentenced to a suspended jail sentence of four years. The French medicines agency, accused of failing to act quickly enough on warnings about the drug, was fined €303,000.[10] The pharmaceutical group was later additionally convicted of charges of fraud.[11]
Fenfluramine, a related drug, had been withdrawn from the market in 1997 after reports ofheart valve disease,[12][13]pulmonary hypertension, and development ofcardiac fibrosis. This side effect is mediated by the metabolitenorfenfluramine on5HT2B receptors of heart valves,[14] leading to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on thetricuspid valve. Both fenfluramine and benfluorex form norfenfluramine as a metabolite. This side effect led to the withdrawal of fenfluramine as an anorectic drug worldwide, and later to the withdrawal of benfluorex in Europe.
^Roger P, Auclair J, Drain P (1999). "Addition of benfluorex to biguanide improves glycemic control in obese non-insulin-dependent diabetes: a double-blind study versus placebo".Journal of Diabetes and Its Complications.13 (2):62–67.doi:10.1016/S1056-8727(98)00004-X.PMID10432168.
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