CV safety in diabetes treatments debated

ADA 70th Scientific Sessions

ORLANDO — Should new diabetes drugs submitted to the FDA have a higher bar for cardiovascular safety than other drugs was the focus of a debate here between Steve E. Nissen, MD, and David G. Orloff, MD.

“Drugs that lower blood sugar can make CV disease worse or they can make it better, and we ought to know which it is before we treat our patients,” Nissen, chairman of the department of CV medicine at Cleveland Clinic, said at the debate. “Clinical outcome trials comparing alternative diabetes therapies are essential to determine the optimal approach to prevent CV morbidity and mortality.”

Nissen maintained the pro position, and said previous FDA requirements were lax in accountability for drug effects beyond blood sugar.

“Regulators said, ‘You don’t have to do an outcome study, you just have to show us that you lowered blood sugar.’ So, they set us up for a 50-year gap in medical knowledge — that was a mistake that finally has been recognized.

This sense of glucosecentricity,” as Nissen called it, led to drugs that were rushed through approval before the effects were fully understood, he said.

Orloff, who had more than 10 years of experience at the FDA before his current post as director of regulatory affairs at Medpace, argued that FDA requirements need more flexibility, based on individual drugs.

“For type 2 diabetes or any disease target, the clinical questions to be addressed will be very different with every program, and we should direct our energies and spending as appropriate and applicable case by case,” Orloff said.

“It certainly seems that integrated drug development programs that approach [from an efficacy standpoint] diabetes-associated conditions such as CVD separately from dysglycemia might constitute a real step forward for patients,” he said. “However, it is not immediately clear why CVD effects become the prime safety concern of all antidiabetic agents.”

Orloff said there are no quick fixes for diabetes, and there is a tremendous amount of work to be done in therapeutics development.

“I'm the last person in this room that wants to stifle innovation in new drug development. I want new drugs, but I don't want more drugs — I want better drugs,” Nissen said. – by Matthew Brannon

I think that the debate went well. Dr. Nissen obviously is very much in favor of new guidance with regards to establishing the CV safety of diabetes drugs, and Dr. Orloff made a good point that perhaps we need to have a more nuanced approach in which, based on available information, we would pursue safety in more diffused ways. Both seemed to be focused on the idea that we need safer drugs to a greater extent than we need more drugs.

– John Buse, MD, PhD
Professor of Medicine and Endocrinology Chief at University of North Carolina, Chapel Hill

For more information:

• Nissen SE. Should new diabetes drugs submitted to the FDA have a higher bar for cardiovascular safety than other drugs? Presented at: The American Diabetes Association 70th Scientific Sessions; June 25-29, 2010; Orlando.

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