FDA Considers Stricter Rules For Diabetes Drugs

Draft guidance could make things tough for companies developing new diabetes medicines. In the wake of the controversy over the diabetes drug Avandia, the U.S. Food and Drug Administration is considering tougher standards for how and when diabetes drugs will be tested for risks to the heart.

Two drug safety advocates who played a key role in the debate over Avandia, made by drug giant GlaxoSmithKline, praised the draft results that were circulated by the FDA Feb. 29. (See full document at fda.gov.)

Last May, Steven Nissen, head of cardiology at the Cleveland Clinic, wrote an article in The New England Journal of Medicine saying that Avandia increased the risk of heart attacks and strokes by 40%. Glaxo took issue with Nissen’s methodology, but Avandia sales plummeted anyway. The drug got stuck with a warning about heart attacks that its main competitor, Takeda Pharmaceutical’s Actos, does not carry.

Glaxo continues to stand behind Avandia’s safety and efficacy. But Nissen and others critics say the company waited too long to start trials to prove that Avandia’s blood-sugar-lowering potential translated into benefits for patients.

Nissen calls the new guidance "a definite step in the right direction." He calls it a "compromise" between insisting that all the data are available when a medicine is approved, which might make drug development so expensive that new treatments would never make it to market, and the current situation: not having big studies start until years after a medicine hits pharmacy shelves, if ever.

An FDA spokeswoman said the guidance did not result from the controversy, but other sources interviewed for this article disagreed.

Clifford Rosen, a researcher at the Jackson Laboratory in Bar Harbor, Maine, who headed up an FDA advisory panel on Avandia’s heart risk, says he is "encouraged" by the new guidance. He says that too often big studies to prove that drugs prevent hard outcomes like heart attacks or death are started too slowly.

"It is setting the stage for some harder times for diabetes drugs," Rosen admits. He sees the message to drug companies as "be careful," because measures of blood sugar alone won’t be enough to get some medicines approved.

One drug Rosen doesn’t see being tarred by the guidance is the long-acting form of Byetta, a diabetes injection sold by Amylin and Eli Lilly. The main putative side effect for that drug is pancreatitis, and the concern is based mainly on case reports.

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FACT:
Shortage Of Deep Sleep May Increase Diabetes Risk: Sleep quality appears to play a role in diabetes risk, according to researchers.  When in an experimental setting, deep, restorative, slow-wave sleep (stages 3 and 4) was suppressed in healthy young adults, there was a 25% decrease in insulin sensitivity, with a rise in the risk of type 2 diabetes. The findings were comparable in diabetes risk to gaining 18 to 29 pounds, and the sleep quality of volunteers in their 20s was that of those in their 60s. Slow-wave sleep is associated with transient metabolic, hormonal, and neurophysiologic changes, all of which could potentially affect glucose homeostasis. The current evidence demonstrates a clear role for slow-wave sleep in the maintenance of normal glucose homeostasis.  Thus, strategies to improve both sleep duration and also sleep quality should be considered as a potential intervention to prevent or delay the development of type 2 diabetes in elderly individuals as well as the obese, Dr. Tasali and colleagues conclude. Reported in the "Proceedings of the National Academy of Sciences."