Why Lorcaserin And Other Weight Loss Drugs Fail To Deliver

Lorcaserin and Cardiovascular Risk?

In addition to the primary objective of weight loss, BLOOM and BLOSSOM phase 3 trials also looked at the drug’s effect on the heart, cardiovascular risk, central fat distribution, mood and other factors. These were necessary investigations because lorcaserin could also activate receptors 5HT2A and 5HT2B. These receptors are activated by serotonin to mediate a number of functions including learning, mood, smooth muscle contraction and inflammation. It was important to assess whether or not lorcaserin may have unintended consequences by affecting these functions.

The way to look at this is to think of lorcaserin as a key that may have the ability to open locks (receptors) that are similar to each other. For example, say you have a car key that can fit the ignition of similar car models. If the engine turns over the car will run (an unintended and unwanted consequence). If it doesn’t quite fit nothing will happen. Arena had to learn if their weight loss drug may affect systems that have nothing to do with appetite. Fortunately, lorcaserin had greater affinity for the 5HT2C receptor (the one that mediates weight loss) meaning that it was less likely to activate the receptors that helped control other functions.

Why was the FDA concerned?

The FDA advisory committee was concerned about lorcaserin’s effect on the cardiovascular, cancer risk, and mental health of consumers. Cancerous tumors in rats was the biggest concern to the advisory panel. It was found that rats that had been administered high doses of lorcaserin developed mammary gland tumors.

Even though Arena speculated that this was caused by a lorcaserin-stimulated prolactin release the FDA was concerned that humans taking lorcaserin may develop cancer. There is also a relationship between serotonin and prolactin which makes it of particular interest to this study which is using a drug (lorcaserin) to mimic serotonin.

Serotonin has been shown to increase prolactin production via a number of receptors including those that maybe activated by lorcaserin. Prolactin is a hormone that has many functions, one of which is facilitating lactation. Although men and women synthesize prolactin its production increases during pregnancy. The hormone has been found to cause breast cancer in some women.


I hold a degree from one of the top ranked research universities in the United States. I am the administrator and publisher of Living Fit, Healthy and Happy which is a family-friendly health and wellness website with articles on fitness, anti-aging, obesity, diabetes, eating disorders, cardiovascular health and many other health related issues. Publishing fitness and healthy living blogs is my way of getting the word out to the public about the benefits of a healthy lifestyle. So on Living Fit, Healthy and Happy I write articles using the pen name "healthy_blogging". I also re-publish the articles of other authors whom I deem to have scientific merit and serve the public interest. In my free time, I enjoy physical fitness, outdoor activities, reading of fiction and nonfiction material, listening to music and spending time with family and friends.

12 thoughts on “Why Lorcaserin And Other Weight Loss Drugs Fail To Deliver

  • November 18, 2010 at 4:11 pm

    Lactulose is a potent laxative. There will be diarrhea, but that is to be expected. Normal side effects are bloating, belly cramps, etc. For patients in advanced kidney failure, things get a bit tricky, as diarrhea means excretion of potassium. Because of that hypokalemia )low potassium) and hypernatremia (high sodium) can ensue. These electrolytes need to be measured carefully in such patients and whoever prescribed the lactulose must know that patient has these health problems. Hope that helps…

  • October 28, 2010 at 12:23 pm

    Hello Jarret and Doug,

    I’m excited by all the buzz that my article has been generating. It’s an important topic and I’m happy for the opportunity to guest post here and that so many people find the article informative.

    I agree that Arena failed to because they only looked at one aspect of obesity. Until the pharmaceutical industry helps consumers address the root causes of the problem, they will never be successful in helping the masses sustain long term healthy body weight.


  • October 27, 2010 at 8:37 am

    Joseph, thanks for the great article on weight loss pills and Locaserin, in particular. 370 retweets is definitely the most we’ve ever seen here at Hive Health Media.

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  • October 26, 2010 at 7:51 am

    One significant hurdle facing any and all obesity drug manufacturers is that obesity is a multi-faceted problem

    Brain chemistry, hormones, genetics, epigenetics, lifestyle, social pressure, advertising, etc….

    So, when a drug like Lorcaserin takes a focused approach (serotonin) to solve a multi-faceted problem, I believe that they are doomed to failure.


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