AHA obesity conference

The AHA sponsored the "Obesity, Lifestyle, and Cardiovascular Disease Symposium" in Washington January 18-19, a conference with a lot of sessions on exercise, better eating, the food pyramid, etc. One particularly interesting talk was by Dr. Susan Yanovski of NIDDK. Dr. Yanovski began with a brief overview of the history of weight loss-inducing drugs, from the use of amphetamines in the 1950’s and 1960’s, their fall from grace between 1973 and 1996, and their recent revival. Her discussion of current and prospective weight loss drugs focused on sibutramine (Abbott's Meridia), orlistat (Roche's Xenical), and rimonabant (Sanofi's Acomplia). Her overall outlook on these drugs appeared to be pretty positive, which was incredibly surprising, since the side effect profile, at least for the first two, has made them nearly non-drugs -- neither is marketed actively, and it was surprising to us she didn't talk more about the evil side effect profiles!

Dr. Yanovski did appear very interested in learning more about rimonabant—how it works, its potential to induce weight loss, and its side effects. She explained that rimonabant is a CB1 receptor blocker but said that she still was not clear on the exact mechanism by which it causes weight loss. In particular, she expressed interest in a study on animals that found that rimonabant caused a decrease intake of palatable foods for the first two weeks, but even after the animals’ diets returned to normal, they continued to lose weight. Was that normal, as it no dieting? Unclear. She invited anyone in the audience to volunteer any thoughts or explanations for this study during the Q&A session after her presentation (no one volunteered any information, although Sanofi was a conference sponsor).

Dr. Yanovski also mentioned two other studies, one current and one from 2005, which have examined the impact of rimonabant on weight loss. Of the current study, she said that she knew of no weight loss drugs that had yet been shown to have an impact on cardiovascular but that two companies are currently looking at this possibility in a study of sibutramine and rimonabant. She said that a study by Van Gaal, published in 2005 in Lancet, had offered the most conclusive evidence showing that rimonabant is an effective weight loss drug. Dr. Yanovski said that the study found that obese patients taking 20mg of rimonabant experienced 10% weight loss, compared to 5% in a placebo group. However, these results were highly concentrated among “responders” – these patients experienced three times as much weight loss as the placebo group. Meanwhile, of course, the patients who did not respond to the rimonabant experienced almost no weight loss and Dr. Yanovski stressed that “non-responders” should not continue receiving rimonabant since they would be at risk for side effects while receiving no benefit from the drug. She did say that “responders” have shown signs of improvement in glucose and insulin levels, increased HDLs, decreased triglycerides, and lower blood pressure. Sibutramine and orlistat also improved lipids, glucose, and insulin, while orlistat also improved BP.

Despite her positive outlook, Dr. Yanovski did not think that rimonabant would necessarily be more effective than the currently available drugs on the market. She believes that there is very little difference among the current drugs. She also found that the drugs all had moderate risks of side effects. She said that rimonabant had been associated with psychiatric disorders such as depression and anxiety, nervous system disorders, and gastrointestinal problems but that more investigation of these effects was necessary. Ultimately, her conclusion was that it is not yet known “how things will play out with this one.” We are more nervous about safety and more upbeat about commercial prospects.

Dr. Yanovski concluded with a brief discussion of off-label use of other drugs to induce weight loss, notably including metformin, exenatide (Amylin's Byetta), and pramlitide (Amylin's Symlin). Her personal recommendation for these drugs was to be very cautious with using them off-label. However, she also stressed that she believes these drugs can be very useful treatments for promoting weight loss in patients who already have the drugs’ primary indication. Overall, it sounds like tacit acknowledgement that some people will use these drugs for weight loss ...