WASHINGTON – New drugs to treat an epidemic of diabetes will have to be screened more closely for heart risks, federal health officials said Wednesday.
The Food and Drug Administration's policy change should offer a greater assurance of safety to doctors and patients. But it will make it more costly and time-consuming for companies to develop drugs that lower blood sugars. Well over 100 such medications are in some stage of development.
"I think the FDA got this one right," said Dr. Steven Nissen, a Cleveland Clinic cardiologist who raised the diabetes concern two years ago with a study indicating a popular new drug increased the risk of heart attacks. The medication, Avandia, remains on the market amid continuing debate. But such drugs will have to clear a higher bar in the future, the FDA said.
Some 23 million people in the U.S. have Type 2 diabetes, which is considered an epidemic among adults, and a concern with teenagers and even children. People with diabetes are unable to properly break down carbohydrates, either because their bodies do not produce enough insulin or because of resistance to insulin. As the years go by, they are at higher risk for heart attacks, kidney problems, blindness and other serious complications.
Because heart attacks are a leading cause of death among diabetics, medications that lower blood sugars but also increase heart risks could easily do more harm than good.
That is particularly true when other treatments are available that do not appear to have heart risks, such as insulin injections or pills like metformin.
Dr. Mary Parks, head of the FDA division that oversees diabetes drugs, said the policy is intended to remove the uncertainty about new diabetes drugs. Separately, the FDA is working on new guidance for already approved diabetes drugs.
"The more we know about the safety profile, the better it is for physicians to make decisions," Parks said.
The policy sets out more rigorous standards for testing diabetes drugs, following recommendations from FDA advisers and critics such as Nissen.
"The idea is not to create such a high barrier that you will stifle innovation in developing new drugs, but to make sure clinicians have the information they need," Nissen. "This will raise the level of evidence available, and that is good for patients."
Currently, people selected to test a new medication are often younger and healthier than the patients who ultimately wind up being prescribed the drug. Under the new FDA policy, drug companies will have to test drugs on greater numbers of high-risk patients, such as the elderly, those with relatively advanced diabetes and those with kidney problems. The studies will have to take longer, which would allow for the emergence of subtle problems, such as gradual increases in blood pressure.
Drug companies will have to set up independent committees to monitor the rates of heart attacks, strokes, and heart-related deaths and hospitalizations linked to drugs in development.
Finally, the companies will have to conduct certain statistical analyses of the results, with an upper limit on how much risk is acceptable for a new drug.
But one bottom-line measure will not change: Diabetes drugs still will be judged on how well they lower blood sugars.
The FDA already sent letters to drugmakers describing the changes, Parks said. Makers of some 100 to 150 medications under development were notified.
"It is safe to assume that if we are going to be requiring a longer duration of trials, that it will add some years, some time to the clinical development process," added Parks.
"This is going to be hard risk to assess for and will add a lot of cost and time to development," Gottlieb said. "You are looking for small risks that only become manifest after prolonged use, so it may often take big, long term studies to uncover these things."