Review of Heart Side Effects for Diabetes Drugs Lead to Delay for Proposed Takeda Medication

Following the discovery of heart problems with Avandia and other diabetes drugs, the FDA is requiring that drug makers establish that proposed diabetes medications do not increase the risk of cardiovascular side effects, even if the New Drug Application was filed before the new guidance was issued in December 2008.

According to a statement released by Takeda Pharmaceutical Co. on March 6, 2009, their U.S. subsidiary was recently notified by the FDA that the new guidelines will be applied to their 2007 New Drug Application for alogliptin, an experimental treatment which was seen as a potential blockbuster medication for type 2 diabetes.

Although the New Drug Application for alogliptin was filed over a year before the FDA issued their guidance about evaluating the heart side effects of diabetes drug, the regulatory agency has indicated they will be unable to complete their review on time because the existing clinical data is insufficient to meet the statistical requirements in the new guidelines.

Alogliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor that would be taken together with exercise and diet by type 2 diabetics. DPP-4 inhibitors are oral anti-diabetics, which maintain the blood levels of the insulin-increasing hormones GIP (glucose-dependent insulinotropic peptide), and GLP-1 (glucagon-like peptide 1), and thus lower blood sugar levels.

The release of alogliptin, also known as SYR-322, was expected to come later this year, but will delayed at least several months while additional clinical studies are conducted to evaluate the potential cardiac side effects.

The FDA decided to intensify their review of proposed diabetes medications after they drew criticism for their handling of the diabetes drug Avandia.

In May 2007, independent researchers published a study in the New England Journal of Medicine which looked at data from over 42 different clinical trials involving over 28,000 diabetics , finding that side effects of Avandia increase the risk of heart attack by as much as 43%.

Although Avandia is effective in helping type-2 diabetics control their blood sugar levels, the side effects could increase the risk of congestive heart failure, heart attacks and death, leading many to question the justification for the continued use of Avandia.

In October 2008, the consumer advocacy group Public Citizen filed a petition with the FDA calling for an Avandia recall, indicating that the risk of potentially fatal heart problems and other side effects outweigh any potential benefit provided by the treatment.

There are an estimated 23 million people in the United States who have type-2 diabetes, and prescription drug treatments for the condition generate billions of dollars annually for the pharmaceutical industry.

Takeda Pharmaceutical Co., the largest drugmaker in Japan, was looking to SYR-322 (alogliptin) to replace lost sales they expect from their current best-selling diabetes drug Actos, which could become available as a generic in 2011.