Key advisor: FDA should hold diabetes drugs to different standard
“Without a regulatory sea change with regard to diabetes drugs, we are certain to be in the same position five years from now that we are in now,” wrote Clifford Rosen, MD, in an online “Perspective” piece for The New England Journal of Medicine. “We will again find ourselves in possession of a new wonder drug that is designed to treat a devastating chronic disease but that may do more harm than good.”
Rosen called the shifting away from surrogates like glycated hemoglobin levels, in favor of clinical outcomes, an “urgent need.” The agency took a similar step 20 years ago, he said, when it altered its end point for osteoporosis drugs from bone mineral density to fractures.
While glycemic control is the basis of therapeutic interventions in type 2 diabetes, it's a “relatively poor” surrogate for cardiovascular outcomes in type 2 diabetes, Rosen noted, accounting for only 5% to 15% of the variation in ischemic risk.
The July 30 advisory committee meeting bore that out. In one of the largest randomized trials of Avandia (rosiglitazone) studies evaluated as part of the meeting—A Diabetes Outcome Prevention Trial (ADOPT)—the percentage decrease in glycated hemoglobin was greater with rosiglitazone than with metformin or sulfonylureas, yet the risks of congestive heart failure and cardiovascular ischemia were higher, he pointed out.
The committee last month voted to keep the GlaxoSmithKline type 2 diabetes drug on the market but said its label should include strict warnings on use.