Belviq: What to do when patients ask

I am acutely aware of the obesity epidemic in this country.  I’ve posted previously about how obesity may have surpassed smoking as the #1 preventabe cause of death in the U.S.  Still the FDA approval today of Belviq, a sertonergic drug that brings back memories of Fen-Phen, Meridia and Redux (dexfenfluoramine) over concerns with their association with valvular heart disease, pulmonary hypertension and other concerns.  The studies to date have been necessarily relatively short term, and the FDA is requiring Arena Pharmaceuticals to do continued aftermarket surveillance for these concerns.

My dilemma as a physician is how to balance the potential benefit of moderate weight loss vs. the potential for side effects from Belviq.   Belviq appears to have some patients who respond well to treatment, while others respond less well.  The anticipated weight loss is more than 5% of body weight over the initial 12 weeks o f therapy, with further weight loss expected in patients who continue therapy.  Some patients will not respond with the anticipated 5% or more weight loss in the initial 12 weeks of therapy and in those patients it is recommended that the Belviq be discontinued.  Obesity is a well-known risk factor for diabetes, degenerative joint disease, and other cardiovascular problems, so it is far from a benign condition.

Belviq is a brand new drug, at least superficially similar to prior drugs that were found to have unexpected serious problems with sustained use, and I would argue that its risks are to some degree TBD (to be determined). The issue in its simplest terms is whether a drug like Belviq which offers a hope for modest weight loss is worth taking when the risks are still ill-defined.  The answer is going to depend on the benefits side of the equation as much as on the risks side. Patient with morbid obesity may be willing and even appropriate candidates for taking more risk for a hope of weight loss because the potential benefits are larger.  Patients with more moderate obesity, in the BMI >30 range for which Belviq has the FDA indication (BMI >27 with other risk factors) may be less likely to get major health benefits, and so the risk-benefit analysis may swing more towards not using the drug as the risks are likely to be just as high for them as in higher risk patients.

My approach for now is going to be to wait a bit to see how the early after-market reports of efficacy and side effects turn out, and if they seem OK to cautiously consider Belviq in carefully selected patients.  An individual’s health risks from obesity are related to much more than their BMI.  Do they also have diabetes, hypertension, congestive heart failure or osteoarthritic hips or knees?  I expect to have patients requesting Belviq soon. I’ve already had patients asking for the generic components of the still-under-review Qnexa (phenermine plus topiramate). I hope that Belviq turns out to be even more safe and effective than the early studies suggest, but I will not be surprised if Belviq turns out to be less effective than early studies suggest and if some so far unfounded fears of cardiovascular side effect risks are realized.

Addendum:

Since the publication of this post, the correctness of the information has been challenged. The crux of the disagreement lies in the specificity of the receptor where Belviq has its function.  Belviq appears to be much more specific to the receptors that affect hunger than those in cardiac tissue, which may allow Belviq reduce hunger, lead to weight loss and avoid the cardiac side effects of earlier drugs that less specifically stimulated this receptor.  I have changed the verbiage of the post to more accurately reflect the expected weight loss from Belviq.

Edward Pullen is a family physician who blogs at DrPullen.com.

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  • REZA GANJAVI

    Doc, these numbers might be of use regarding efficacy:

    47.5% of patients who took Lorcaserin lost at least 5% of their weight versus 20.3% for placebo patients. Of those completing the studies, 63.9% lost greater than 5% of their weight, 34.7% lost greater than 10% of their weight, and the top 25% lost over 16.7%. The average completer weight loss was 26 pounds or 8.2%. It has been scientifically proven that even a 5% drop in weight can result in meaningful improvements in overall health.

  • http://twitter.com/ReligionRetards MaryWasAVirgin?..Nah

    Kevin, you are unaware to the specifics of how this drug was created so you are fearful of it due to your ignorance of the pharmacology of the drug. It has been engineered through many years of testing and fine tuning well before the first human studies began to specifically target only the 5HT2c (hunger) receptor while Fenfluramine is a potent agonist of the 5HT2b receptors that are in the heart and valves. The 2+ years and nearly 10 thousand patients taking Lorcaserin continuously without a single signal for CV risk is a testament to the science behind the creation of this novel new drug which is why the doctors recommended a powerful 19-4 vote for approval and why the FDA approved Belviq without any label restrictions. In fact, the side effects of Belviq are resoundingly the safest when compared all the other Diabetes and weight management drugs with the worst side effect being a slight headache that goes away.
    Further, your data concerning percentage weight loss which you state is important in your consideration is at best, inaccurate and at worst, incorrect. The average weight loss for patients that complete Belviq therapy is 8% with 1/3rd losing over 10% of their body weight and 25% of patients losing a tremendous 16.7% of their body weight. For you to deny a potential patient of Belviq the opportunity to lose 10% and more of their weight because of your ignorance of the medication is not in their best health interests, especially considering how Belviq users showed improved diabetes markers across the board.
    I challenge you to take the time to learn the details of the studies and how the medication works and you will understand why it is safe and very effective for your patients and why the FDA approved it.

  • mwch

    Dr. Pho — I think you mis-state the risk/reward ratio when you say that Belviq provides “modest weight loss, hoped to be at most 5% of body weight in 12 weeks.” The fact is that Belviq is recommended to be discontinued if the weight loss at 12 weeks is not AT LEAST 5% (not “at most” 5%). In just 12 weeks, non-responders will be identified & will stop treatment, thus obviating any risk. Responders (those who do lose at least 5% within 3 months) go on to lose, on average, 11% of their body weight. So that degree of weight loss will produce substantial health benefits to balance against unknown risks.
    An additional benefit of Belviq, not often mentioned, is that a study trial of Type II diabetics demonstrated excellent blood glucose improvement — an average reduction of 0.9 in HbA1c –this reduction was approximately twice the improvement of placebo patients who lost the same amount of weight.

  • rswmd

    I’d delete these advertisements. They couldn’t even be bothered to read the by-line on the original post!

  • http://www.facebook.com/chuck.bennett.543 Chuck Bennett

    Respectfully, your lack of research on this drug is a disservice to your patients. I for one am looking forward to prescribing this revolutional drug to assist in the obesity epidemic. You question its safety and that’s good to do for any new drug but again,it appears you didn’t look at what the studies revealed. Belviq has been tested for ten years on nearly 10,000 patients. These studies included serial echocardiograms on thousands of patients over years without increased CV risk. The studies also showed stat sig DECREASES in HR as well as surprisingly beneficial effects on HgA1c which was lowered by 0.9%-comparable to many NIDDM drugs. It also had a significant effect on cholesterol and TG’s in particular. In sum, Belviq looks to be an excellent drug not just for obesity, indeed it seems tailored for metabolic sydrome in reducing numerous CV risk factors. Similarly, your efficacy and MOA comments are also off the mark by a wide margin. In the interest of your patients and other MDs who follow your blog, I would encourage you to look more closely at this drug; it’s a big step forward for patients.
    DrChuckMD

  • andybaron

    Dr. Pullen seems not only to be ignorant of the efficacy and safety data from Arena’s 3 phase III clinical trials, but also to be fairly ignorant of the medical benefits of weight loss.

    For example:

    “Belviq, a sertonergic drug that brings back memories of Fen-Phen, Meridia and Redux (dexfenfluoramine) over concerns with their association with valvular heart disease, pulmonary hypertension and other concerns.”

    Dr. Pullen completely ignores the extensive research findings on Belviq’s very specific activation of the 5HT2C receptor. It is outrageous to blindly lump lorcaserin in with fenfluramine and dexfenfluramine, which activated the 2B receptor associated with heart tissue as much as they activated the 2C receptor associated with satiety. Sibutramine (Meridia) broadly blocks the re-uptake of both serotonin and norepinepherine, which is also released by phentermine. Two years of careful Belviq testing on nearly 8,000 test subjects failed to show any CV signal. Valvulopathy findings were in the 2% range, below what is expected in the general population. Fen-Phen caused valvulopathy in 20%-30% of patients and well within two years.

    “The studies to date have been necessarily relatively short term, and the FDA is requiring Arena Pharmaceuticals to do continued aftermarket surveillance for these concerns.”

    The aftermarket CVOT studies are being conducted to measure relative rates of major cardiovascular events, such as stroke and heart attacks. Such studies have been recommended for all weight loss drugs, even when no CV signal is detected, to test whether the weight reduction correlates with improvements in mortality and morbidity. These studies are long-term because it takes time until people start dying or having strokes, not because there is concern that extended exposures will reveal previously unknown side effects.

    “My dilemma as a physician is how to balance the potential benefit of modest weight loss, hoped to be at most 5% of body weight in 12 weeks with the potential for long-term side effects from Belviq.”

    Dr. Pullen’s claims of modest weight loss and “at most 5%” are not supported by any data. He seems to have pulled that figure out of thin air based on some foggy recollection of the advice to discontinue use after 12 weeks unless there has been 5% weight loss. In fact those who completed a year on Belviq averaged 8.2% weight loss, and if you count only the “responders” who lost at least 5% then the average was 11%. It is outrageous again that Dr. Pullen can bring in diabetes without even mentioning the stellar effects Belviq had on glycemic measures (.9% reduction in HBA1C, which was .5% greater than placebo, and a 27% reduction in fasting blood sugar). In addition, he ignores the clear medical evidence that even “modest” 5% weight loss can reduce the risk of diabetes by 60% (http://eurheartjsupp.oxfordjournals.org/content/7/suppl_L/L21.full).

    “The issue in its simplest terms is whether a drug like Belviq which offers a hope for modest weight loss is worth taking when the risks are at best ill-defined.”

    The fact that few risks emerged in the clinical trials does not mean they are ill-defined.

    “The answer is going to depend on the benefits side of the equation as much as on the risks side. Patient with morbid obesity may be willing and even appropriate candidates for taking more risk for a hope of weight loss because the potential benefits are larger. Patients with more moderate obesity, in the BMI >30 range for which Belviq has the FDA indication (BMI >27 with other risk factors) may be less likely to get major health benefits, and so the risk-benefit analysis may swing more towards not using the drug as the risks are likely to be just as high for them as in higher risk patients.”

    Another outrageous statement, blithely tossed out as if it were medical wisdom when in fact it is completely false. Weight loss of 5%-10% is at least as valuable for obese patients as for overweight patients, even though they may still be obese after the weight loss. This is especially true for diabetes risk.

    “My approach for now is going to be to wait a bit to see how the early after-market reports of efficacy and side effects turn out, and if they seem okay, to cautiously consider Belviq in carefully selected patients.”

    So, he has more faith in hearing anecdotal evidence based on early aftermarket reports than in large, two-year, double-blind, placebo-controlled clinical trials.

    “An individual’s health risks from obesity are related to much more than their BMI. Do they also have diabetes, hypertension, congestive heart failure or osteoarthritic hips or knees?”

    Well, that’s exactly why the label calls for such comorbidities being present if BMI is under 30. Those with obesity-level BMI are demonstrably at greater risk for developing these conditions, if they aren’t already present.

    “I hope that Belviq turns out to be even more safe and effective than the early studies suggest, but I will not be surprised if Belviq turns out to be less effective than early studies suggest and if some so far unfounded fears of cardiovascular side effect risks are realized.”

    It’s hard to imagine how Belviq could turn out to be safer than early studies suggest, unless fewer people end up with transient headaches — the only adverse event that occurred over 5% more in active than placebo arms of the trials. There were no clinical safety signals in the phase III studies, and the efficacy observed was clearly adequate to support widespread use of Belviq.

  • REZA GANJAVI

    Great post Andy. This is grounds for demanding a retraction correction or deletion of Dr. Pullen’s junk piece — people can’t expect to publish trash and just get away with it. Kevin, you will hear from us.

  • http://www.facebook.com/joseph.dedvukaj.92 Joseph Dedvukaj

    The first thing you should do when a patient asks is be honest. There are “potential theoretical risks” with crossing the street, driving a car, flying in an airplane, using any medicine, etc. however, you are not true to the clinical trials and selectivity studies done on Belviq. I assume you have the ability to comprehend the science involved, but it does not appear you have actually researched Belviq to advise your patients that over 8000 patients in the Belviq studies showed ZERO evidence of Heart issues. The selectivity studies proved Belviq is 105 times more selective to the 2c receptor controlling appetite than the 2b receptor known to cause heart issues. Stick to the science doctor. Now then tell your patients about the clinical evidence of the dangerous side effects with Qnexa use. In the long term use of Phen/Tpm this can cause brain damage. A strict REMS will be used because doctors like you will abuse prescribing this drug. I’ll bet many doctors will circumvent the REMS program and dangerously prescribe the ingredients you mentioned are currently available because their cheaper and less time consuming to prescribe the ingredients. Qnexa offers nothing new to the physicians arsenal for the reasons you confirm – the ingredients have been around for years. If you care to respond be honest to the science and cite from the evidence the FDA experts studied. There is no REMS requirement for Belviq because the issue you speak of has been proven by selectivity studies to be virtually nonexistent. Joseph Dedvukaj, attorney at law.

  • EmilyAnon

    It’s interesting that all the vociferous attackers of this story are first time posters on Kevin’s blog, but heavy contributors to the financial news website, The Street, to any news story dealing with stocks and Big Pharma. Maybe they’re heavy investors in Belviq reacting to a call to action to stamp out any negative reports on the drug.

    • Ari Faynerman

      While some of what you said is true, pretty much all of it minus the vociferous attackers part, you should realize that what the responses are saying is fact not fiction. Of course we would attempt to stomp out blatant lies, half truths, and selective data that portrays an actually safe efficacious drug as one that is neither. And I am sure all of us understand that not everybody has the time to do their due diligence before posting, so we corrected the good doctor as we saw fit. These are not lies we are spreading but factual truths, read the clinical trial data and not the opinions of people and you will agree.

  • rswmd

    It’s a troll party!

  • http://twitter.com/VanessaObRN VanessaObRN

    to Reza, and the other Arena Pharma investors who posted here:
    Reza, you have posted a negative review of this article because you are an investor in Arena Pharmaceuticals. In your online journal, you gloat about the current success of the company and its association with Belviq and actually thank God that “after so much pain in the market, you finally have a (financially) comforting day”. All you care about is your bottom line. Not exactly an altruistic motive for trumpeting a controversial drug.

  • http://www.facebook.com/people/Tom-Fitzsimmons/1405121136 Tom Fitzsimmons

    OK, I’m not one to scream “big pharma is coming!” but looking at these comments I think it might be appropriate. I find the tenor of these objections too well organized and too cookie cutter perfect. Well done though. I’ve seen this sort of manipulation many times but rarely so skillfully done.

  • http://www.facebook.com/people/Tom-Fitzsimmons/1405121136 Tom Fitzsimmons


    I for one am looking forward to prescribing this revolutional drug to assist in the obesity epidemic”. Nobody talks like this. Nope!

  • http://pulse.yahoo.com/_UNHTD45P2TRASVJLXU4BCKIHIY Sam

    Dr. Pullen you obviously did very little research before posting untruths about the “low” 5% weight loss on Lorcaserin/Belviq from Arena Pharmaceuticals. Ed Sussman, a reporter from the same web site as your article (MedPageToday) lost 55lbs in one year, while on the
    Lorcaserin/Belviq patient study, which is 18% of his body weight. See this article.
    http://www.medpagetoday.com/PrimaryCare/Obesity/33723

  • http://www.dpsinfo.com LaurieMann

    People need to unlearn their bad habits. Lost two grandfathers to smoking, one of whom did manage to quit smoking about a year before emphasema killed him. It took my father 49 years to unlearn how to smoke, but now he’s a fairly active man in his early 80s, so I’m glad he did! My mother lost a lot of weight in her 50s, and I’m glad she did, too. I’ve been spending a lot of time unlearning my bad eating habits – more activity, less junk food. I still have a way to go, but I’ve lost 65 pounds over 16 years; finally dropped into the overweight BMI category after being in the obese BMI category for nearly 30 years. I’m on Benicar, but look forward to the day when I won’t have to take any extra medication (beyond vitamins). I think if schools and doctors studied and promoted nutrition in a more positive way, we’d all be in better shape and we’d be taking less drugs.