FDA releases new recommendations for evaluating CV risk in drugs for type 2 diabetes

The FDA recently recommended that manufacturers developing new type 2 diabetes drugs provide evidence that the therapy will not increase the risk for cardiovascular events such as myocardial infarction.

The recommendation is part of a new guidance for industry that applies to all diabetes drugs currently under development. People with diabetes have a two- to four-times greater risk for heart disease than those without diabetes, yet none of the currently approved antidiabetic therapies has been proven to reduce CV risk, according to an FDA press release.

“We need to better understand the safety of new antidiabetic drugs; therefore, companies should conduct a more thorough examination of their drug’s cardiovascular risks during the product’s development stage,” Mary Parks, MD, director of the Division of Metabolism and Endocrinology Products, Center for Drug Evaluation and Research, said in a press release.

Stronger evidence needed

The FDA guidance defined more robust and adequate design and data collection approaches for phase-2 and phase-3 clinical trials. The agency recommended that trials demonstrate that new antidiabetic therapies do not increase CV risk compared with existing therapies, particularly when patients of advanced age or with advanced diabetes or renal impairment use the drugs.

The FDA also recommended that committees of outside cardiologists analyze any CV events to ensure that product labeling includes comprehensive information on safety and effectiveness.

“The FDA’s guidance and its ongoing evaluation of this issue supports our approach to drug regulation throughout the product lifecycle, by evaluating a drug’s safety before and after its approval,” Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, FDA, said in a press release.

The FDA remains confident that currently marketed antidiabetic therapies are safe and effective when used according to approved labeling. The FDA is continuing to evaluate how the recommendations will be applied to already approved antidiabetic drugs and expects to release further guidance in the future.

The FDA has issued draft guidance, which formulates a policy designed to quantify coronary heart disease risk and a means to evaluate it in diabetes products that are in phase-2 and phase-3 development. Their creation of a meta-analysis strategy by which to determine the extent of CHD risk vs. comparators during the development program must yield a CHD risk ratio within acceptable bounds. For ratios of 1.8 or greater preapproval studies will be required for new drug application submission, as they should. For low ratio products with ratios less than 1.3, further studies may not be essential to the approval process. For agents with intermediate CHD risk ratios of 1.3 to 1.8, generally post-marketing studies will likely be required and linked to the approval process.

This guidance imposes certain experimental design requirements for all phase-2 and phase-3 trials to insure that an accurate meta-analysis can be performed upon the phase-2 and phase-3 trials data to generate a useful CHD risk ratio to comparator (placebo).

These steps by the FDA clearly act to ensure the continuing health and safety of the U.S. diabetic population while assuring the ongoing availability of new and improved agents for better diabetes control in America.

– Alan J. Garber, MD, PhD

Endocrine Today Chief Medical Editor