Few dispute the need for better drugs to treat obesity. In the US and around the world, obesity rates are soaring, driving the prevalence of related conditions like diabetes, and lowering lifespan. Lifestyle modification is only moderately successful at reducing weight in most patients, and bariatric surgery, though highly successful at reducing weight, is highly invasive, has safety concerns, and is not recommended for any patients with a BMI under 40 or 35 with a comorbid condition. Drugs currently lie somewhere in between lifestyle modification and surgery with respect to efficacy and invasiveness. Potentially damaging side effects of currently approved drugs are worse than dieting alone, but better than bariatric surgery. Tolerability is also an issues with many weight loss drugs. As a number of obesity experts have said, the eventual goal for obesity drugs should be to have the effectiveness of bariatric surgery, with the safety of lifestyle intervention.
Few dispute the need for better drugs to treat obesity. In the US and around the world, obesity rates are soaring, driving the prevalence of related conditions like diabetes, and lowering lifespan. Lifestyle modification is only moderately successful at reducing weight in most patients, and bariatric surgery, though highly successful at reducing weight, is highly invasive, has safety concerns, and is not recommended for any patients with a BMI under 40 or 35 with a comorbid condition. Drugs currently lie somewhere in between lifestyle modification and surgery with respect to efficacy and invasiveness. Potentially damaging side effects of currently approved drugs are worse than dieting alone, but better than bariatric surgery. Tolerability is also an issues with many weight loss drugs. As a number of obesity experts have said, the eventual goal for obesity drugs should be to have the effectiveness of bariatric surgery, with the safety of lifestyle intervention. Many obesity experts believe that safe drugs will become as effective as bariatric surgery, although this will clearly not happen overnight. Over 350 anti-obesity drugs are currently in development, and many of them are very promising, but in our view, the truly novel drugs are many years from becoming available to patients.
So how are drugs for obesity going to reach the effectiveness of bariatric
surgery? Current obesity drugs help people lose around 7% body weight, whereas
bariatric surgery causes people to lose up to about 40% body weight – certainly the numbers vary person
to person, but it is clear that drugs have a long way to go. Some obesity
experts such as Dr. Louis Aronne of
Cornell University and Dr. Richard Atkinson of Obetech Obesity Research Center
have spoken highly of using
combinations of drugs, rather than a single one, in lower doses.
The rationale behind using several drugs, these experts explain, is that obesity is controlled by many things in our own bodies including numerous hormones – hormones called ghrelin, PYY, leptin, and amylin to name a few. When one of these hormones is targeted to lower obesity, the other hormones usually fight back. This response (it's called a counterregulatory response) is one of the reasons why current obesity drugs are not particularly effective. Current drugs often change the level of only one hormone, and therefore the effectiveness of the drugs are limited by the other hormones. The idea of combination therapy is not to target only one hormone, but to target numerous hormones, and eliminate the counterregulatory response – to set the whole weight regulation system into free fall, sort of speak. Another advantage of using low doses of numerous hormones is that side effects are often reduced, because side effects are exacerbated by higher dosages. Of course, it will be some time before effective and safe low dose combination therapies become available to patients, but progress is being made. One recent study by Amylin Pharmaceuticals that we found particularly intriguing showed that the combination of two hormones, leptin and amylin cause about 13% weight loss in humans, matching the results previously seen in animal studies. This leptin/amylin combination is currently in phase 2b, and Amylin is currently doing further study to determine whether this will be appropriate to try to bring to market. We hope that effective and safe combination therapies become available sooner rather than later.
amylin is the hormone, not pramlintide
but we get what you mean
sorry to nitpick
Posted by: Mags | 12/21/2007 at 10:08 PM