Servier, the drug’s manufacturer, is accused of deceiving users over the killer side effects of a drug later used to treat overweight diabetics.
Believed to be one of France’s biggest healthcare scandals, the firm is on trial for manslaughter and deceit.
Servier has denied the charges, saying it did not lie about the side effects.
French health experts believe the drug known as Mediator could have killed anywhere between 500 and 2,000 people before it was finally taken off the market in 2009.
The country’s state drug regulator, accused of not acting to prevent deaths and injuries, is also on trial.
The trial will involve more than 2,600 plaintiffs and 21 defendants, and is expected to run over the course of six months.
It will also look into why the drug, which was introduced in 1976, was allowed to sell for so long despite various warnings.
Lawyers representing the plaintiffs argue that the drug manufacturer purposely misled patients for decades, and that this was bolstered by lenient authorities.
Servier has been accused of profiting at least €1bn ($1.1bn, £880m) from the drug’s sales.
“The trial comes as huge relief. Finally, we are to see the end of an intolerable scandal,” Dr Irene Frachon, a pulmonologist credited with lifting the lid on the side effects, told Reuters news agency.
Dr Frachon’s research drew on medical records across France and concluded that there was a clear pattern of heart valve problems among Mediator users. This prompted many more studies which ultimately led to the drug’s ban.
One study concluded that 500 deaths could be linked to Mediator between 1976 and 2009. A second one put the figure at 2,000.
Those numbers have been disputed by Servier, which has said that there are only three documented cases where death can be clearly attributed to the use of Mediator. In other cases, it says, aggravating factors were at work.
Servier has said it will continue to compensate victims and has paid almost €132m to patients.
“There is a series of circumstances highlighting how all this took place,” a lawyer for the drug company told Reuters.
Several European countries, like Spain and Italy, banned the drug in the early 2000s.
Based on a molecule called benfluorex, Mediator was first developed in 1976 as a lipopenic – a drug to lower fat levels in the blood.
Later, it was prescribed to diabetics to help them lose weight.
But as its appetite-suppressant properties were recognised, family doctors began offering Mediator as a general treatment. Anyone worried about putting on the pounds could be offered a course of the drug – even though legally it was authorised for diabetics alone.
By the time it was taken off the market, it is believed that some five million people had taken Mediator, making it among the 50 most-prescribed drugs in France.