The drug maker Eli Lilly has engaged in a 10-year effort to downplay the health risks of Zyprexa, its best-selling medication for schizophrenia...

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The drug maker Eli Lilly has engaged in a 10-year effort to downplay the health risks of Zyprexa, its best-selling medication for schizophrenia, according to hundreds of internal Lilly documents and e-mails among top company managers.

The documents, given to The New York Times by a lawyer representing mentally ill patients, suggest Lilly executives kept important information from doctors about Zyprexa’s links to obesity and its tendency to raise blood sugar, both known risk factors for diabetes.

Lilly’s published data, which it told its sales representatives to play down in conversations with doctors, have shown that 30 percent of patients taking Zyprexa gain 22 pounds or more after a year on the drug, and some patients have reported gaining 100 pounds or more.

But Lilly was concerned Zyprexa’s sales would be hurt if the company was more forthright about the fact the drug might cause unmanageable weight gain or diabetes, according to the documents, which cover 1995 to 2004.

Link denied

Critics, including the American Diabetes Association, have argued that Zyprexa, introduced in 1996, is more likely to cause diabetes than other widely used schizophrenia drugs.

Lilly has consistently denied such a link and did so again Friday in a written response to questions about the documents. The company defended Zyprexa’s safety and said the documents had been taken out of context.

The drug

Zyprexa has become Lilly’s best-selling product by far, with sales of $4.2 billion last year, when about 2 million people worldwide took the drug.

Its chemical name is olanzapine, and it is used to treat such illnesses as schizophrenia, other psychotic conditions and bipolar disorder.

It is one of a class of drugs called atypical anti-psychotics that includes Johnson & Johnson’s Risperdal and AstraZeneca’s Seroquel.

The drug’s maker, Eli Lilly, based in Indianapolis, is the sixth-largest U.S. drug-maker, with $14 billion in revenue last year.

The New York Times

But as early as 1999, the documents show that Lilly worried that side effects from Zyprexa, whose chemical name is olanzapine, would hurt sales.

“Olanzapine-associated weight gain and possible hyperglycemia is a major threat to the long-term success of this critically important molecule,” Dr. Alan Breier wrote in a November 1999 e-mail to 24 Lilly employees that announced the formation of an “executive steering committee for olanzapine-associated weight changes and hyperglycemia.”

Hyperglycemia is high blood sugar.

At the time, Breier, now Lilly’s chief medical officer, was the chief scientist on the Zyprexa program.

In 2000, a group of diabetes doctors that Lilly had retained to consider potential links between Zyprexa and diabetes warned the company that “unless we come clean on this, it could get much more serious than we might anticipate,” according to an e-mail from one Lilly manager to another.

And in that year and 2001, the documents show, Lilly’s marketing research found that psychiatrists were consistently saying that many more of their patients developed high blood sugar or diabetes while taking Zyprexa than other anti-psychotic drugs.

The documents, which until last week remained under court seal, were collected for lawsuits on behalf of mentally ill patients against the company.

Last year, Lilly agreed to pay $750 million to settle suits by 8,000 people who claimed they developed diabetes or other medical problems after taking Zyprexa. Thousands more suits against the company are pending.

On Friday, in its written response, Lilly said it believed Zyprexa remained an important treatment for patients with schizophrenia and bipolar disorder.

The company said it had given the Food and Drug Administration (FDA) all its data from clinical trials and reports of adverse events, as it is legally required to do. Lilly also said it shared data from literature reviews and large studies of Zyprexa’s real-world use.

“In summary, there is no scientific evidence establishing that Zyprexa causes diabetes,” the company said.

Lilly also said the documents should not have been made public because they might “cause unwarranted fear among patients that will cause them to stop taking their medication.”

How effective?

Some psychiatrists said Zyprexa will continue to be widely used despite its side effects, because it works better than most other anti-psychotic medicines in severely ill patients.

But others said Zyprexa appears no more effective overall than other medicines.

Some doctors who specialize in diabetes care disputed Lilly’s assertion that Zyprexa does not cause more cases of diabetes than other psychiatric drugs.

“When somebody gains weight, they need more insulin; they become more insulin resistant,” Dr. Joel Zonszein, the director of the clinical diabetes center at Montefiore Medical Center, said when asked about the drug.

In 2003, after reviewing data provided by Lilly and other drug makers, the FDA said the current class of anti-psychotic drugs may cause high blood sugar. It did not single out Zyprexa, nor did it say the drugs had been proved to cause diabetes.

The Zyprexa documents were provided to The New York Times by James Gottstein, a lawyer who represents mentally ill patients and has sued Alaska over its efforts to force patients to take psychiatric medicines against their will. Gottstein said the information in the documents raised public-health issues.

“Patients should be told the truth about drugs like Zyprexa,” Gottstein said.

Lilly called the release of the documents “illegal.”

The company said it could not comment on specific documents because of the continuing product-liability suits.

Lilly has never conducted a clinical trial to determine how much Zyprexa raises patients’ diabetes risks.

But scientists say conducting such a study would be exceedingly difficult, because diabetes takes years to develop, and it can be hard to keep mentally ill patients enrolled in a clinical trial.