FDA wants closer scrutiny of new diabetes drugs

With type 2 diabetes already increasing heart risks, the FDA is seeking assurances that new drugs won't do further damage.

By Susan J. Landers — Posted Jan. 12, 2009

Print  |   Email  |   Respond  |   Reprints  |   Like Facebook  |   Share Twitter  |   Tweet Linkedin

The Food and Drug Administration is asking the manufacturers of new drugs and biologics for type 2 diabetes to be more diligent in determining if their therapies pose cardiovascular risks.

Until now, manufacturers had only to show that their drugs reduced blood sugar levels.

"We need to better understand the safety of new antidiabetic drugs," said Mary Parks, MD, director of the agency's Division of Metabolism and Endocrinology Products at the Center for Drug Evaluation and Research. She released a guidance document outlining the agency's recommendations for doing such an assessment Dec. 17, 2008.

More than 23 million people in the U.S. have been diagnosed with type 2 diabetes, which places them at a two- to four-times greater risk of heart disease than their nondiabetic counterparts. None of the currently approved antidiabetic therapies has been proven convincingly to reduce that risk, the FDA said.

The guidance, which is effective immediately, asks that phase II and III clinical trials demonstrate that new therapies do not increase cardiovascular risk in comparison with existing therapies.

The FDA also recommends to manufacturers that any cardiovascular events occurring in their trials be analyzed by committees of outside cardiologists.

The FDA already has placed black-box warnings on one class of type 2 diabetes drugs, thiazolidinediones, or TZDs, after they were found in postmarketing studies to increase the risk of heart failure. Two drugs, Avandia, or rosiglitazone, and Actos, or pioglitazone, are in that class.

Alarms about Avandia's association with increased heart risks were raised in a May 2007 New England Journal of Medicine article by Steven Nissen, MD, chair of Cleveland Clinic's Dept. of Cardiovascular Medicine. At the time, Dr. Nissen noted that because of this risk, Avandia is not a drug he recommends to patients.

GlaxoSmithKline, the manufacturer of Avandia, strongly disagreed with the conclusions in the NEJM article, faulting the authors' reliance on a meta-analysis rather than on long-term trials that Glaxo said showed no increased cardiovascular risk associated with Avandia.

Meanwhile, in a study published online Dec. 10, 2008, by the Canadian Medical Assn. Journal, researchers found that the risk of fractures doubled among older women who take TZDs for one year or more to control their diabetes.

"We knew going into this study there was an association between thiazolidinediones and fracture risk. However, the magnitude of the risk had not been evaluated," said Sonal Singh, MD, MPH, an assistant professor of internal medicine at Wake Forest University School of Medicine in Winston-Salem, N.C., and a co-researcher for the study.

Glaxo responded that the bone fracture risk had been reported previously and is noted on the Avandia label. A study to evaluate the effects of the drug on bone in women with type 2 diabetes is now enrolling participants, a spokesman said.

But in a commentary published online Dec. 10, 2008, in the CMA journal, Lorraine L. Lipscombe, MD, an adjunct researcher at the Institute for Clinical Evaluative Sciences in Toronto, recommended that TZDs not be considered a first-line therapy for type 2 diabetes.

"If a patient is unable to take other therapies or if other therapies have failed, there may be a role for thiazolidinediones in carefully selected patients duly informed of the potential adverse effects," she wrote.

Back to top


Rationale behind guidance

The persistent need to quantify the risks associated with anti-diabetic drugs has spurred Food and Drug Administration action on the topic. The reasons are:

  • More than 23 million people in the U.S. have been diagnosed with type 2 diabetes or diabetes mellitus.
  • Patients with diabetes have a two- to four-times greater risk of heart disease than do their nondiabetic counterparts.
  • None of the currently approved antidiabetic therapies has been convincingly proven to reduce that risk.
  • Because diabetes often requires lifelong treatment, prescribers and patients need to know more about whether their antidiabetic therapies put patients at increased risk of heart attack.

Source: Food and Drug Administration, December 2008

Back to top

External links

Food and Drug Administration recommendations on evaluating cardiovascular risk in type 2 diabetes drugs, Dec. 17, 2008 (link)

"Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis," Canadian Medical Assn. Journal, online Dec. 10, 2008 (link)

Back to top



Read story

Confronting bias against obese patients

Medical educators are starting to raise awareness about how weight-related stigma can impair patient-physician communication and the treatment of obesity. Read story

Read story


American Medical News is ceasing publication after 55 years of serving physicians by keeping them informed of their rapidly changing profession. Read story

Read story

Policing medical practice employees after work

Doctors can try to regulate staff actions outside the office, but they must watch what they try to stamp out and how they do it. Read story

Read story

Diabetes prevention: Set on a course for lifestyle change

The YMCA's evidence-based program is helping prediabetic patients eat right, get active and lose weight. Read story

Read story

Medicaid's muddled preventive care picture

The health system reform law promises no-cost coverage of a lengthy list of screenings and other prevention services, but some beneficiaries still might miss out. Read story

Read story

How to get tax breaks for your medical practice

Federal, state and local governments offer doctors incentives because practices are recognized as economic engines. But physicians must know how and where to find them. Read story

Read story

Advance pay ACOs: A down payment on Medicare's future

Accountable care organizations that pay doctors up-front bring practice improvements, but it's unclear yet if program actuaries will see a return on investment. Read story

Read story

Physician liability: Your team, your legal risk

When health care team members drop the ball, it's often doctors who end up in court. How can physicians improve such care and avoid risks? Read story

  • Stay informed
  • Twitter
  • Facebook
  • RSS
  • LinkedIn