A growing number of drug makers and doctors are examining whether medications already used to treat patients with diabetes can help prevent the disease in others who are at risk of developing it, potentially creating a vast new market for the pharmaceutical industry.
Several companies, including GlaxoSmithKline PLC of the U.K., Takeda Pharmaceutical Co. of Japan and Novartis AG of Switzerland, are studying how their existing drugs that treat diabetics work in people who don't yet have the full-blown illness. Other drug makers, such as Amylin Pharmaceuticals Inc. and Eli Lilly & Co., both of the U.S., are also looking into the diabetes-prevention market. And some doctors in the U.S. already are prescribing diabetes drugs to patients who appear likely to progress to having the condition, even though the Food and Drug Administration hasn't approved any drugs for that use.
The market for a diabetes-prevention drug could be huge -- perhaps $15 billion a year, according to some analysts. There are an estimated 54 million people in the U.S. with "pre-diabetes," which means that their scores on blood-sugar tests are higher than normal but still not elevated enough to be classified as having Type 2 diabetes, the American Diabetes Association says.
In Type 2 diabetes, the more common type, the patient doesn't produce enough insulin, or his cells ignore the insulin, which is a hormone that is needed to convert sugar and other food into energy. In Type 1, no insulin is produced. The proposals to use drugs for preventing diabetes generally focus on Type 2.
But the spreading idea of prescribing diabetes drugs to prevent the disease is raising concerns for the FDA and others. The big issue: Why use a prescription drug to avert a disease that studies show can often be effectively prevented through a careful diet and exercise? In addition, some diabetes drugs have been linked to side effects, such as heart failure and weight gain.
The ADA recommends weight loss and exercise and says "drug therapy should not be routinely used to prevent diabetes" until there is more information about its cost-effectiveness. "Lifestyle therapy provides for a much greater range of benefits," says John Buse, president-elect of the ADA, which will examine the issue again as new study results emerge.
Supporters of using existing diabetes medicines to prevent the disease say it could be useful for those who haven't been able to drop pounds or start working out. Lifestyle improvements are important, but "it's somewhat unrealistic to say it's the only tool that we should have," says David Nathan, a Harvard University professor who led a major National Institutes of Health study on preventing diabetes.
Daniel Vasella, chief executive of Novartis, says "diet and exercise are of primary importance." But an effective drug could also play an important role in prevention, he argues. "It's not either/or. It's both," he says. The company has begun a trial to test its drug Galvus in diabetes prevention, though it is still waiting to hear whether it has won FDA approval to sell galvus for the treatment of existing diabetes. A decision is expected by year's end.
The major diabetes medications mostly work by helping to improve patients' control over their blood sugar. The idea behind diabetes-prevention drugs is that these medications can have similar effects on people who are at an earlier stage of developing the problems that characterize the disease -- particularly an impaired ability to clear sugar from the blood.
In a trial published last month in the medical journal the Lancet, the GlaxoSmithKline drug rosiglitazone, known by the brand name Avandia, reduced the risk of developing diabetes or dying by more than half compared with a placebo in people at high risk for diabetes. At the end of the study, 11.6% of the 2,635 people given Avandia developed diabetes or died, compared with 26% of the 2,634 given a placebo. All patients were advised to eat healthily and exercise.
Lawson Macartney, senior vice president for developing diabetes and cardiovascular drugs at Glaxo, says there is a "strong scientific rationale" for treating patients during the early signs of blood-sugar problems. Improvements in diet and exercise should be the first form of treatment, he said. Medication could also "potentially" be appropriate if the FDA approves a drug for diabetes prevention, he added. He wouldn't comment on whether the company will file for FDA approval to sell Avandia for diabetes prevention.
In the NIH trial headed by Dr. Nathan, an older drug called Glucophage, or metformin, now available generically, reduced the incidence of diabetes by 31%, while intense lifestyle changes cut it by 58%.
But if people don't make the lifestyle changes they should, "that doesn't mean they shouldn't be treated with medication," says Ralph DeFronzo, a professor at the University of Texas Health Science Center in San Antonio who is leading a trial to test the preventative effects of Actos, a diabetes drug from Takeda that is similar to Glaxo's Avandia. He already prescribes drugs to some prediabetic patients, he says.
But other doctors remain skeptical. For one thing, they warn, patients may be less likely to improve their diet and exercise if they think a pill can prevent diabetes. In addition, doctors and regulators are wary of any safety concern with drugs used by people who aren't sick and may never develop diabetes. In the recent Avandia study, for instance, patients who took the drug were more likely to have nonfatal heart failure, with a rate of 0.5%, compared with 0.1% in those taking a placebo. Also, patients taking Avandia gained more weight during the trial than those taking a placebo.
Glaxo says the rate of side effects seen in the trial was similar to those of other Avandia trials.
Another question for doctors, and the FDA, is what drug makers must do to prove their drugs truly do avert diabetes. If medicines can improve blood-sugar measurements in pre-diabetic people, "does that really mean they're preventing disease?" says Robert Meyer, who heads the FDA office that oversees diabetes-drug reviews.
Dr. Meyer says the agency won't necessarily require studies that focus on proving that diabetes-prevention medications avert the serious complications tied to diabetes, which drug makers say could take a decade or more. But even if a study's main finding was about blood-sugar test scores, "we would certainly be looking at clinical outcomes" such as heart attacks, strokes and eye damage as well, he says. The FDA is working on guidelines about diabetes drugs, and, more broadly, the agency plans a meeting and other efforts focused on how to test drugs to prevent diseases.
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