Humans and other animals produce serotonin, a protein hormone that plays a role in appetite. It binds to specific cell receptors including the 5HT2C serotonin receptor and thus regulates hunger. Lorcaserin is a weight loss drug that was designed to mimic the action of serotonin and bind to the 5HT2C receptor to suppress appetite. On the outset this seems logical because if a person doesn’t feel hungry they’ll feel less inclined to eat. But nothing is ever so simple.
There was a serious flaw in Arena’s research. The problem with lorcaserin’s studies is that the drug trials were not representative of the general population. After initial testing, Arena selected just over 7000 candidates for two phase 3 trials of lorcaserin’s efficacy as a weight loss drug.
The BLOOM Trial for Lorcaserin?
BLOOM which is an acronym for Behavioral Modification and Lorcaserin for Overweight and Obese Modification was the first phase 3 trial. This study took place over a two-year period and involved 3182 overweight or obese males and females who were randomly assigned to either a lorcaserin group (receiving 10 mg twice a day) or a placebo group (receiving an inert substance that doesn’t do anything for or to the body).
BLOOM’s had two main objectives, the was to assess lorcaserin’s effect on weight over the course of a year. The second top objective was to determine if patients who received lorcaserin could keep the weight off during the second year. In other words, to test whether or not lorcaserin would cause weight loss and help patients keep it off. *
BLOSSOM Trial for Lorcaserin
The company also conducted a second phase 3 trial called BLOSSOM for Behavioral Modification and Lorcaserin Second Study for Obesity Management. This study was only one year in duration and involved 4008 overweight or obese males and females. This group also had an objective which was to determine if lorcaserin could cause weight loss over the course of one year. There was a difference between the BLOOM and BLOSSOM studies. BLOSSOM patients were randomly assigned to one of three groups: a group receiving 10 mg of lorcaserin twice a day; a group receiving 10 mg lorcaserin once a day; or a placebo group.
But the company immediately мейд a serious error because the sample sizes were far too small to give a clear picture of how lorcaserin would affect the health of people who took the drug. In other words there is no way to know if lorcaserin is safe for human use. To have an accurate picture they should have taken a much larger sample size. And according to the FDA review, the BLOSSOM study had to be revised because it was initially designed for less than 4000 candidates.
Although it is scientifically impossible to have perfect confidence in the outcome of any study i.e. there will always be uncertainties, unintended consequences and side effects, large sample sizes provide considerable data, and increases the accuracy of the results. Only Arena knows why they selected a relatively small population.
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, 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.
Lorcaserin and Cancer Risk?
But it wasn’t just breast cancer. Rats also developed tumors of the nerve tissue, brain, and skin. This is very significant as humans who took the drug may also develop such diseases later in life. Obesity already increases cancer risk among susceptible populations. Drugs such as lorcaserin could inadvertently increase cancer risk even further. So you can see there is a reason to be cautious about this particular drug considering the risk of multiple cancers that have been linked to it.
This Is Your Brain on Drugs?
Lorcaserin also has a tendency to affect judgment and other cognitive abilities. Some patients reported difficulty with memory, recognition and concentration. Even more disconcerting, as noted in the FDA lorcaserin review appendices, other patients reported depression and suicidal thoughts. Some of those patients did not even have a reported history of depression prior to enrolling in the lorcaserin drug program.
To me, just reading the online version of the FDA review, these side effects stood out as a huge red flag. Considering the fact that in order for the drug to be effective it had to be taken on a regular basis, prolonged use of lorcaserin may have impaired ability to make complex decisions, performance of task, and sense of well-being. That becomes a rather remarkable unintended negative side effect which could have long-term adverse consequences for life, work, and recreational activities.
How Effective Is Lorcaserin for Weight Loss?
Although lorcaserin was effective helping a number of patients lose weight (greater than or equal to 5 percent body weight was lost), it still performed only slightly better than the weight loss achieved by those taking placebo. Put another way, people who did not even take the weight loss drug lost almost as much weight as those who took lorcaserin.
For those who lost weight while taking the weight loss drug, it is difficult to ascertain whether other possible contributing factors including weight loss counseling, adhering to a reduced calorie diet, maintaining a food and activity diary, and exercise – all of which were part of the study program could have had a greater effect on the weight loss results than the drug itself.
It’s very important to point out that a considerable number of patients did not complete the phase 3 trials and it is unknown whether or not they were successful in losing weight and maintaining weight loss.
Perhaps Arena Pharmaceuticals can try again. But there’s something that we all need to think about. The major problem of weight loss drugs is that people who want to take medications for weight loss are also more inclined to seek out an easy fix for their problems.
Weight loss products often fail to attack the root of the problem: commitment. The majority of people with weight problems are less committed to taking long-term steps to change their lifestyle in favor of improved health. It is easy to start out fast and strong when you’re first out of the gate, but eventually most people are going to experience a.
This is perfectly natural, but it can be very frustrating and some people can be so discouraged that they fall back into old habits. Even taking the lorcaserin weight loss drug required a commitment; patients had to take it every day so in order for it to continue to be effective for appetite suppression.
And that’s just taking a few moments each day to take one’s meds. Think how much more one has to do if he/she is going to lose weight. Selecting healthy foods, getting regular exercise, getting enough sleep, etc. This can be annoying and bothersome for people who have grown so accustomed to the habits and behaviors that led to their weight problem that they may not be willing to do those things long-term.
What are you willing to sacrifice to get what you want?
Guys, if you want to wear 31 inch jeans and get the V taper, are you able to give up that six-pack of beer?
Women who dream of having the sexy , it won’t happen unless you’re prepared to give up something in your diet or lifestyle.
Shortened Lifespan
Sedentary lifestyle,, poor food choices, etc. are habits that are linked to. Even if you’re a person with low self-esteem issues, or uses food as an emotional crutch (i.e. eating even when you don’t feel hungry), if you sincerely want to turn your life around, you’ll do it. Feeling it within the very fiber of your being that you can make your life what you want it to be, you’ll sacrifice to get what you want.
That’s the key to long-term weight loss or any other life success. And you can’t get that in a pill. It must come from within.
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