Skepticism about science and medicine

In search of disinterested science

Posts Tagged ‘lorcaserin’

Anti-obesity drug-peddling (Anti-obesity fuss III)

Posted by Henry Bauer on 2014/09/04

There is no epidemic of obesity: there is only an epidemic of eating unhealthily and too much (Anti-obesity fuss part I). However, official reports (Anti-obesity fuss part II) and professional organizations abet Big Pharma’s re-definition of lifestyle issues as conditions to be treated medically, including by drugs and even surgery. As is all too typical, the risks associated with drugs fail to be emphasized, and there is no demonstration that the possible benefits of medical intervention exceed those risks.

“In carefully selected patients, appropriate drugs can augment LCDs [low-calorie diets], physical activity, and behavior therapy in weight loss. Weight loss drugs that have been approved by the FDA for long-term use can be useful adjuncts to dietary therapy and physical activity for some patients with a BMI of ≥ 30 with no concomitant risk factors or diseases, and for patients with a BMI of ≥ 27 with concomitant risk factors or diseases. The risk factors and diseases considered important enough to warrant pharmacotherapy at a BMI of 27 to 29.9 are hypertension, dyslipidemia, CHD, type 2 diabetes, and sleep apnea. Continual assessment by the physician of drug therapy for efficacy and safety is necessary” (p. xx in [1], emphases added).

All this may seem unexceptionable, yet it is dangerously misleading:

  •  In the real world of actual medical practice, patients are far from “carefully selected”, and prescriptions are written without the doctor having good evidence that the prescribing actually augments rather than replacing what should have been tried first and for some reasonable length of time, namely diet.
  •  The naming of BMI ranges where drugs are appropriate depending on “concomitant risk factors” makes no sense since that range of BMI, 27 to 29.9, is already itself such a risk: “All . . . adults . . . with a BMI of ≥25 are considered at risk for developing associated morbidities or diseases such as hypertension, high blood cholesterol, type 2 diabetes, coronary heart disease, and other diseases” (p. xii).
  • FDA-approved drugs have often had to be later withdrawn because the initial approval was unwarranted. Thus “At the present time [1998], sibutramine is available for long-term use” (p. xx), but it was withdrawn in 2010 “based on information from a recent clinical study”  showing increased incidence of heart attack and stroke.
    Why had that not shown up in pre-approval clinical trials?
    That question is rhetorical and cynical. Clinical trials submitted in support of drug approval are carefully designed and chosen to emphasize benefits and to mask deleterious “side” effects. It is normal for later studies to show more harm and less benefit [2].
    But even in 1998, the risk-to-benefit ratio did not look good. “It enhances weight loss modestly and can help facilitate weight loss maintenance” [emphases added] hardly describes something that is genuinely effective; on the other hand, “side” effects weree known to be potentially serious: “increases in blood pressure and heart rate may occur.”

In 1998, orlistat was being considered for approval, which was soon granted. Orlistat disrupts the body’s normal fat-metabolizing mechanisms in order to decrease the absorption of fat in the diet. In 2010, the Food and Drug Administration issued a warning about potentially severe liver damage from orlistat, either the prescription form (Xenical, 120 mg) or the over-the-counter[!] version (Alli, 60 mg).
Another rhetorical question: Who would have guessed that disrupting the body’s fat-metabolizing mechanisms could cause liver damage (as well as Lord knows what else)?

Our bodies are complex systems in which substances and mechanisms are shared and interact in many ways, with feedbacks and regulators. It is naïve, stupid, ignorant, to imagine that one can disrupt one reaction or mechanism without producing multiple effects; yet drug treatments are based on that mistaken assumption. Hence “side” effects are universal, and all too often they are significanty harmful. For example, the same reaction pathway that generates cholesterol also generates ubiquinone (Coenzyme Q10) which is an essential part of the body’s energy-producing reactions; therefore weakening of muscles is an inevitable “side” effect of statins (Statins: Scandalous new guidelines; Statins weaken muscles by design).

The peddling of anti-obesity drugs proceeds even as their claimed benefits are small to non-existent. It is reported that lifestyle changes alone can yield weight loss of about 10% in a year (pp. xxv, xxvi in [1]), yet the FDA’s criterion for approving anti-obesity drugs is an even smaller weight loss (p. 7 in Guidance for Industry Developing Products for Weight Management):

“In general, a product can be considered effective for weight management if after 1 year of
treatment either of the following occurs:
• The difference in mean weight loss between the active-product and placebo-treated
groups is at least 5 percent and the difference is statistically significant
• The proportion of subjects who lose greater than or equal to 5 percent of baseline body
weight in the active-product group is at least 35 percent, is approximately double the
proportion in the placebo-treated group, and the difference between groups is statistically

This trivial goal has allowed approval of drugs that turned out to be lethal. Fen-phen (fenfluramine/phentermine) damaged lungs and heart valves and yielded damages of billions of dollars to subsequent law-suits. Sibutramine, once approved for long-term use had to be withdrawn only a dozen years later (I’m reminded of the monument I saw in Strasburg in 1958: “The Thousand-Year Reich — 1933-1945”).

These drugs suppress appetite by acting on the brain’s neurotransmitters, primarily serotonin, in other words they mess with brain functioning, affecting substances that are involved in much more than appetite, for example serotonin is targeted also by anti-depressants.

Since this Guidance for Industry had been published in 2007 and labeled a “guidance document . . . distributed for comment purposes only”, I sought a later version. There is none [3]:
“The 2007 Draft Guidance for Industry Developing Products for Weight Management is the most up to date version of the guidance. Unfortunately this guidance is not final and we do not have an estimated date of when this will become final”.
These blog posts were stimulated by recent plaudits for purportedly brand-new anti-obesity drugs:
“Not a moment too soon — Why new diet drugs, Belviq and Qsymia, are just in time”.
According to this story, more than one-third of the USA population is obese and 300,000 die annually from “related complications”.

However, these “new” wonder drugs are the same thing all over again.

Belviq ((lorcaserin) “is a serotonin 2C receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults” [emphases added].
It should only be used if diet alone hasn’t worked, and it messes up brain function, so it’s not at all surprising that its “side” effects include “potentially life-threatening serotonin syndrome . . . . confusion, Cognitive Impairment, disturbances in attention or memory . . . , Psychiatric Disorders including euphoria and dissociation, . . . depression or suicidal thoughts” [emphasis added] as well as priapism (erections lasting longer than 4 hours) [4].

Qsymia® (formerly QNEXA) goes one better than Belviq by combining two medicals, phentermine and topiramate. Phentermine is an amphetamine that was part of fen-phen: “deemed safe but was not effective in weight control without its [heart-failure-inducing] partner [fenfluramine]”.  Its new partner, topiramate, “previously FDA-approved for epilepsy. . . . is unrelated to any other drug . . . . No one really knows how topiramate works on the brain, exactly, but it seems to influence a wide range of neuropsychiatric symptoms”.
So Qsymia also messes up brain functioning — moreover in a manner that isn’t understood! — so again it’s no surprise that its “side” effects include suicidal thoughts or actions, depression, anxiety, agitation, panic attacks, insomnia, irritability, aggression, anger, violence, acting on dangerous impulses, mania . . . . As well as increased heart rate and serious eye problems, sudden decrease in vision that could bring permanent blindness (About Qsymia).

The merest hint of these possible “side” effects ought to disqualify these drugs from being used in anything other than cases of imminently life-threatening obesity. It is nothing short of absurd to suggest, let alone recommend, that over-eating should be treated with drugs that disrupt the body’s fat metabolism or the brain’s functioning.

However, the interests vested in drug-based anti-obesity measures are vast. Bureaucracies and jobs are at stake, and research careers. The decisive interest, though, comes from the drug industry. Big Pharma is fixated on blockbuster drugs, things that many people will take over long periods, hence the relentless marketing of statins, blood-pressure- and blood-sugar-lowering drugs, bone-density-increasing drugs, etc.
Big Pharma has no interest in anti-obesity drugs to treat that tiny proportion of people who might actually need them, those with hereditary (”endogenous”) obesity. Instead there are intensive advertising campaigns to convince doctors as well as the general public that drugs are an appropriate way to combat the epidemic of over-eating.

This is yet another illustration that drug companies nowadays market diseases [5] in order to sell supposed remedies. Perfectly normal conditions are “medicalized” by equating them with their extremes: that feeling low, disappointed, grieving, is essentially the same as debilitating clinical depression, say; that declining libido with increasing age is “erectile dysfunction”; that blood pressure higher than normal for twenty-year-olds constitutes “hypertension” [6] and so on and on.

[1] National Heart, Lung, and Blood Institute in cooperation with The National Institute of Diabetes and Digestive and Kidney Disease, Clinical Guidelines on the Identification , Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report, Publication 98-4083, September 1998, National Institutes of Health
[2] John P. A. Ioannidis, “Why most published research findings are false”, PLoS Medicine, 2 (2005) 696-701; “Contradicted and initially stronger effects in highly cited clinical research”, JAMA, 294 (2005) 218-28
[3] E-mail of 22 August 2014 from “CDER DRUG INFO” <>
[4] Belviq®, revised 08/2012
[5] Moynihan & Cassels. Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All Into Patients, Nation Books (2005) and many others, see “What’s wrong with present-day medicine” 
[6] Henry H. Bauer, “Seeking Immortality? Challenging the drug-based medical paradigm”, Journal of Scientific Exploration, 26 (2012) 867-80

Posted in conflicts of interest, legal considerations, medical practices, prescription drugs, science policy | Tagged: , , , , , , , , , , , | Leave a Comment »

%d bloggers like this: