The Byetta Mystery

The biggest mystery about Byetta is why some people are so successful at losing a lot of weight on it and others are not. I know people who have lost more than 60 pounds in less than a year on Byetta. Yet I hear of others who have lost very little weight, if any.

The answer may be in our genes.

Even though I knew about Byetta long before it became available, I didn’t start on it myself until February 6th. (I wrote about my initial results here ). Full disclosure: I own stock in Amylin, which developed and sells Byetta.

One reason why I didn’t start on Byetta earlier was that the official “Prescribing Information” documented an average weight loss of just about six pounds in 30-week clinical trials. The first doctor whom I tried to get a prescription from was not impressed and refused to prescribe it for me.

It wasn’t until I read and reviewed a new book by a great endocrinologist, Dr. Joe Prendergast, that I was inspired to take Byetta myself. The tipping point for me was when he told me that the average weight loss of some 200 patients he has had on Byetta since the first of them started in May 2005 is 35 pounds.

So I asked him if he has noticed differences between his patients on Byetta who lose weight and those who don’t. Do all of those who lose weight go on a low-carb or low-GI diet? Do they have more nausea, so they eat less to avoid it? Do they eat right after a shot, or do they wait almost an hour?

“None of those things seem to matter,” Dr. Joe replied. “I keep trying to have a good solid explanation – plausible – but enough data is not available. The whole thing may take twenty years to unwind.”

Another of my favorite endocrinologists, Dr. William C. (Reddy) Biggs, is as puzzled by this difference. Calling Byetta by its technical name, exenatide, he told me, “I haven’t found a good indicator that will predict a good response to exenatide.”

But he goes on to says that when he starts people on Byetta, he stresses the importance of diet in order to maximize the benefits of the medicine. “My impression of those who fail to lose weight is that they are not experiencing the bloating and fullness when overeating, and find that they are able to eat as much as they want.”

That is likely to be a big piece of the puzzle. The question remains, why are some people able to keep overeating on Byetta?

The answer to this question may well be genetic. Some preliminary scientific research indicates that some of us may have a polymorphism or mutation in the receptor for GLP-1, which is the site of action for Byetta. People often use the terms “polymorphism” and “mutation” interchangeably. But technically a mutation is a rare change in a DNA sequence, while a polymorphism is a common variation.

Dr. Biggs, an endocrinologist practicing in Amarillo, Texas, led me to this recent research, as he has to so much else. For example, it was Dr. Biggs who first told me about what became Byetta in June 2001, when it was still called AC2993 (synthetic exendin-4).