Obesity Drugs and Our Dance with Risk

Physician Ken Fujioka had an Op-Ed in the Post yesterday decrying the FDA's excessive concern about risk in drugs to treat obesity:

There have been enormous leaps in our understanding of the causes of obesity — insights into metabolism, breakthroughs in perspective on craving. It is quite clear that once someone gains weight, the body will turn on a host of defense mechanisms to maintain that higher weight. Most people are trying to fight biology and not just “habits” when they try to lose weight.

Unfortunately, we’ve been stymied by an unrealistic and naive conversation about the risks and benefits of medications to manage obesity. Yes, there are risks with any medication, but there are even more serious risks with obesity and the associated cruel treatment of the obese inherent to our society. It has been more than a decade since doctors have had a new obesity drug to work with.

Three new therapies went before the Food and Drug Administration in the past year, and the agency found all three provided reasonable weight loss that physicians desperately need to manage patients. Yet none of those drugs has been approved; the FDA found them wanting because of concerns about their risks.

I am not arguing that there are not risks associated with medical therapy for obesity. But even the theoretical risks pale next to the risks of undertreating obesity. As a doctor on the front lines, I’ve seen hundreds of patients — hardworking, medically conscientious people — progress to diabetes, cardiovascular disease and degenerative joint disease. I’ve seen patients lose their feet, kidney function and vision to complications from diabetes and obesity. I’ve seen lives cut short and families devastated by heart disease. These are not hypothetical risks of obesity. This is what I see daily.

I know nothing particular about the drugs the FDA has rejected, but there is a real issue here. Critics of the FDA often say that Penicillin could not be approved today, because it is dangerous to so many people. That is probably not true, because the FDA will approve dangerous drugs if there is no other way to treat life-threatening conditions. Since Penicillin was, when it emerged, the only treatment for many infections, it probably would have won approval, albeit with stringent warnings. The FDA has been very reluctant to approve drugs for the treatment of obesity because there is, after all, a safe alternative: eat less and walk more. Judged against that standard, any drug is likely to seem too risky.

What Dr. Fujioka is saying is that this standard is unrealistic, because so many patients can't lose weight that way. Instead the safety of drugs to treat obesity should be judged against the risk of untreated obesity, or against other drugs.

I have a feeling that the FDA is taking the right approach here. After all, none of these drugs "cures" obesity, they just help patients lose more weight and keep it off longer than they would have otherwise. The health benefits of such temporary weight loss are currently obscure and might be small. After all, some studies have shown that it isn't weight in itself that causes ill health, but poor diet and lack of exercise, so people might lose lots of weight with drugs but still suffer from obesity-related illness. Or maybe not, but we really don't know. I am personally skeptical of all the numbers thrown around about the medical cost of obesity. Diabetes is related to weight in a direct way, but for heart disease and other conditions weight is only one factor and it may turn out to be a proxy for other conditions like depression, stress, poverty, agoraphobia, and so on.

Against this possibility of modest health gains for some people you have to weigh the disaster of fen-phen, which helped a lot of people lose weight but killed at least 50 through pulmonary hypertension and led to $14 billion in legal claims. If I were with the FDA I would move very cautiously here, too.