Obesity Drugs

Bill Cheswick

January 2007

I believe that in the next 5--10 years there will be prescription drugs available that will be highly effective against obesity. There will be no fat Americans who don't want to be fat. Poor folk? Some generics will be available in that time frame, at accessible prices. And given the medical costs of obesity, there will be strong incentives to provide treatment to those who can't afford it.

These are nothing like the traditional diet-suppressing drugs. They are new classes of compounds that will simply cut your appetite, with few side effects.

The first of this new class of drugs was approved in Europe last year, and is already available in the UK. It is called Rimonabant, and it the first CB1 blocker, the munchies receptor that THC (pot) stimulates. The FDA is looking at it now, and taking its sweet time. This is one of those cases where their caution is almost certainly causing more problems than it is preventing. I am considering a trip to the UK to get started on the stuff.

It is possible that Rimonabant is not the answer. About one third drop out of the studies. There may be other effects that haven't shown up. But it is only one of several hundred candidates that are working their way through the system. This is an obvious money-maker, and we have a much better understanding of the neurochemistry involved than we did 20 years ago.

And the side effects of not taking it are well known: insulin resistance, heart disease, possibly increased cancer risks, stroke, gout, and joint problems from the extra weight to name a few.

Some say that taking a pill is the easy way out, and not the answer. One doctor at Renaissance Weekend advised that "it is not nice to fool with mother nature." It is true that there are risks with treatment, but Mother Nature has plans for all of us: reduced mitochondrial number and efficiency, DNA damage, cross-linked proteins, and exponentially-increasing cellular senescence.

Another complaint goes along puritanical lines: obesity is caused by a failure of will, by moral laxity. Calories in always equals calories out. People these days, especially Americans, have less moral strength than the skinnier folks of the past.

Actually, the cause of increased American obesity is unclear, despite news stories and movies to the contrary. Obviously we are eating more: an international traveller is immediately struck by the different portion sizes in European restaurants. American restaurants serve huge amounts of food.

But I ate that those restaurants in my twenties, and did not gain weight until I got older. Many women find this is a problem at menopause. My weight in those days was not the result of strong moral values, but different balances in dietary feedback loops. Those balances change with aging, and the pills will be able to move them back.

These feedback loops---the weight set point---is very strongly controlled. Consider your annual caloric intake, and the stability implied in one's weight. It is true that calories-in equals calories-out, but only completely relevant when the victims are not eating ad libitum. Anyone can lose weight in a Turkish prison.

Blaming people for their weight is an attitude that society and the medical profession must get over. It is exactly equivalent to the old belief that ulcers were caused by stress, and if those type-A personalities would just simmer down, they wouldn't be sick. Wrong. It was H. Pylorii, an infectious agent, and it is even possible that obesity has an infectious component.1

People do lose weight, especially after something like a cardiac scare or the death of a loved one. A number of diet plans do work for a while. But people don't stick with them over the long run. Whenever I confront someone with a weight-loss plan, I ask them to apply the same criteria to the plan as we do for cancer cure: how are things five years later. The five-year success rate of diets and life-changing efforts is around five percent, I understand (I would love a reference here: data is scarce.) Certainly it matches my personal observations. Most advocates can't give five-year "cure" rates for their obesity treatments. Also, it is possible that losing and regaining the weight ("weight cycling") is worse than not losing at all. This is controversial and was reviewed in 1994,2 but at least some recent work seems to support the possibility further.3,4,5,6

As for me, there are more than a half-dozen clinical studies of Rimonabant recruiting at the moment, and I appear to be eligible for most of them. I am giving it a try.


1Bajzer, M., Seeley, R., Obesity and gut flora. Nature 444, 1009–1010 (2006).

2Schulz, M, et. al., National Task Force on the Prevention and Treatment of Obesity. Weight Cycling. JAMA 1994; 272: 1196–1202.

3Tsai, Chung-Jyi, et. al., Weight Cycling and Risk of Gallstone Disease in Men. Arch Intern Med. 2006; 166, 2369–2374.

4Saami, S.E., et. al., Weight cycling of athletes and subsequent weight gain in middleage. International Journal of Obesity (2006) 30, 1639–1644.

5Montani, J-P, et. al., Weight cycling during growth and beyond as a risk factor for later cardiovascular diseases: the 'repeated overshoot' theory. International Journal of Obesity (2006) 30, 858–866.

6Schulz, M, et. al., Associations of short-term weight changes and weight cycling with incidence of essential hypertension in the EPIC-Potsdam Study. Journal of Human Hypertension (2005) 19, 61–67.