Taken from the September/October 2010 issue of the Women's Health Activist Newsletter.
This is not the final word; the FDA doesn’t have to follow the advisory committee’s recommendations and, in this case, because the committee gave such mixed messages about Avandia, any decision the FDA makes about keeping it on the market will please one faction and not the other. We hope that the FDA will yank this drug off the market, as it should have done three years ago, the last time Avandia was on the chopping block.
In 2007, the first time the advisory committee considered Avandia’s fate, members voted 20-3 in support of the assessment that Avandia increases the risk of heart attack. Then, inexplicably, they voted 22-1 to recommend keeping it on the market. This time around, the members weren’t even that consistent. Twelve of 33 panelists voted to recommend taking Avandia off the market, while 17 voted for it to stay on the market with restrictions and/or new warnings on the label about the increased risk for heart attacks. Three panelists recommended that Avandia remain on the market with its label unchanged, and one member abstained.
Advisory committee members voted 21-3 (with 9 voting undecided) that data on Avandia “raise significant safety concerns” regarding the risk of heart attacks and other problems, compared to data on unrelated diabetes drugs. The Committee voted 18-6 that the data raise significant concerns that Avandia might cause more heart problems than Actos. Nine members voted “undecided” on both safety votes.1 Although panelists were purportedly vetted for conflicts of interest, conflicts have been identified since the meeting. One endocrinologist who voted to keep Avandia on the market is a paid speaker for GlaxoSmithKlein (GSK), Avandia’s manufacturer.2 Another member who voted against the drug is a paid speaker for Takeda, which makes Actos.3
After the 2007 meeting, the FDA asked GKS to conduct a trial to compare the effects of Avandia and Actos on heart attacks, stroke, and cardiovascular death in diabetics. The resulting Thiazolidinedione Intervention with Vitamin D Evaluation (TIDE) trial, has enrolled more than 1000 patients; but, in late July, the FDA put the trial on hold, forbidding additional enrollment of patients for the time being. The TIDE trial has been decried as unethical. David Graham, an FDA scientist who has criticized the FDA’s handling of Vioxx and other risky drugs, told USA Today that the TIDE trial is “treating humans as if they are laboratory rats. Why on Earth would anyone want to be randomized to Avandia in a clinical trial, the purpose of which is to prove with absolute certainty that Avandia increases risk?”4 We couldn’t have put it better ourselves.
Graham authored a study that was published in The Journal of the American Medical Association (JAMA), which found that, compared to Actos, Avandia increased the risk of stroke, heart failure, and death.5 Not that we want you to get too excited about Actos, either. Avandia may be Actos’ evil twin, but both drugs are in a newer class of diabetes drugs that may not benefit diabetics at all. The goal of treating diabetes isn’t just to lower blood sugar, but also to prevent the disease’s horrid long-term complications, including heart attacks, kidney failure, and blindness. If the goal of taking a drug is to prevent cardiovascular disease, but the drug causes cardiovascular disease, that’s not a win.
The prevalence of both diabetes and coronary heart disease (CHD) increase with age. Data from the Third National Health and Nutrition Examination Survey (NHANES III) show that, regardless of racial and ethnic origin, the prevalence of diabetes doubles as women transition from reproductive years (ages 15-44) to mid-life (ages 45-64). About 2.7 million women aged 40-59 have diabetes. Among women aged 60 or older, about 4.5 million women are diabetic, although 1.2 million of them are undiagnosed. CHD is more prevalent among women with diabetes than those without diabetes. For example, in the Nurses Health Study (NHS), women with diabetes aged 33-55 years had a seven times greater risk for CHD than non-diabetics of the same age. Even after adjusting for other CHD risk factors (obesity, high blood pressure, and high cholesterol), diabetes tripled the risk for CHD.
Because the U.S. is experiencing an on-going tsunami of diabetes, outcomes in diabetes treatment have immense repercussions for public health. Even a relatively small increase in CHD among diabetics results in a tremendous burden of illness and premature deaths, as well as attendant health expenditures.
Between 2007 and 2010, prescriptions for Avandia dropped from 5.6 million to 1 million. That’s still one million too many prescriptions for us. Why should anyone take a drug that increases risk for cardiovascular disease when safer drugs are available? Avandia’s patent expires in 2012, at which time the drug will die a well-deserved, but sorely belated, death.
Moreover, it’s disconcerting that the safety debate seems to be only between these two drugs when there are many other drug treatments (and non-drug treatments) for diabetes. In fact, modifying diet and increasing exercise are the cornerstones of treatment for adult-onset (or Type II) diabetes. Some diabetics will need oral drugs, while others will need insulin. For those who need an oral drug, the classic drug metformin has been shown to be beneficial. There are also many other drugs available that lower diabetics’ blood sugar, although questions remain about whether their long-term benefits also outweigh the risks.
Here’s hoping the FDA does the right thing and pulls Avandia from the marketplace. Our recommendation: don’t take Avandia. If you, or anyone you know, is taking Avandia, you should confront the prescribing provider with information about its risks. If your insurance company has Avandia on its formulary, it should also be questioned. And, if you’re diabetic, every effort you put toward controlling your blood sugar with diet and exercise is a very wise investment with multiple benefits!
Charlea T. Massion, MD, is a practicing physician in Santa Cruz County specializing in hospice and palliative care. Charlea brought her passion for improving women’s health along with 40+ years of health care experience to the NWHN as a member of the board for 8 years. She also co-founded the American College of Women’s Health Physicians.
Adriane Fugh-Berman, MD, is a former NWHN Board Chair whose research presents a critical analysis of the marketing of prescription drugs. Adriane educates prescribers on pharmaceutical marketing practices as Director of the PharmedOUT program, and created the Health in the Public Interest program at Georgetown University School of Medicine where she trains a new generation of consumer advocates.
The continued availability of external resources is outside of the NWHN’s control. If the link you are looking for is broken, contact us at [email protected]to request more current citation information.
Beckles and Thompson-Reid, editors. Diabetes and Women’s Health Across the Life Stages: A Public Health Perspective. http://www.cdc.gov/diabetes/pubs/pdf/women.pdf
1. Rubin R, “Majority of FDA panel votes to keep Avandia on the market,” USA Today, June 14 2020. Available online at: http://www.usatoday.com/news/health/2010-07-14-avandia-diabetes-fda_N.htm.
2. Mundy A, “FDA Panelist's Vote On Glaxo Drug Raises Questions, Wall Street Journal, July 23, 2010, http://online.wsj.com/article/BT-CO-20100723-713822.html
3. Mundy A, “Glaxo Rival Paid Fees to Doctor Who Voted Against Avandia, Wall Street Journal, July 20 2010, http://online.wsj.com/article/SB1000142405274870472360457537929280375504...
4. Rubin R, “FDA to consider fate of diabetes drug Avandia,” USA Today, June 9 2010, available online at: http://www.usatoday.com/news/health/2010-07-10-AVANDIA09_ST_N.htm
5. Graham, DJ, Ouellet-Hellstrom, R, MaCurdy, TE, et al., “Risk of Acute Myocardial Infarction, Stroke, Heart Failure, and Death in Elderly Medicare Patients Treated With Rosiglitazone or Pioglitazone,” JAMA 2010; 304(4):411-418.