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Why We Need Medications For Obesity



sharma-obesity-medications6Regular readers will know of my support for bariatric surgery. Despite all caveats (discussed in previous posts), it remains the most effective (and perhaps only feasible) option for many struggling with severe obesity.

However, even under the best circumstances, surgery is not a realistic option to deal with an epidemic that affects millions of individuals. Even with 10,000 surgeries a year, it would only take about 100 years to operate on every eligible patient in Canada, who is severely obese today. This is neither feasible nor affordable.

Thus, numbers dictate that overweight and obesity will require treatments that can be taken by millions.

To use an analogy: if there were no pharmacological treatments for hypertension or diabetes and the only treatment was an operation, most people would still be dying of heart disease and other complications that are now perfectly preventable and treatable because we have a large armamentum of anti-hypertensive and anti-diabetic medications.

Yes, people could perhaps do more to prevent getting hypertension and diabetes in the first place – we know that healthy diets and regular exercise go a long way in preventing both conditions – but even if we can adopt prevention measures that miraculously cut the incidence of these conditions in half – we are still left with millions who will have hypertension and diabetes.

If we had no drugs, some of these folks may get some relief by reducing their salt intake or following a strict diet – but we know that in real-life, these interventions are neither realistic nor powerful – without anti-hypertensive and anti-diabetic medications we would certainly not have seen the recent remarkable (over 50%) reduction in cardiovascular diseases – we are seeing far fewer strokes and heart attacks than ever before despite an increasingly overweight and obese populations, an increased prevalence of risk factors (except perhaps smoking) and an aging population.

The only reasonable explanation for this decline is the widespread use of highly effective and “proven” medical treatments for these conditions.

While it is impossible for 10s of millions of people to be operated upon, there is nothing to stop 10s of millions of people taking a tablet or two everyday if it helps lower their blood pressure or control their blood glucose.

These medications were not discovered or tested overnight. It took decades of medical research and innovation to develop the wide range of anti-hypertensive and anti-diabetic medications we have today – medications that are more effective and far safer than the drugs that were around when I graduated from medical school.

Every reader, who has anyone in their family with heart disease or diabetes, has probably benefited from the fact that we have these medications.

Although we have these medications to treat high blood pressure and diabetes, these are only two of the many complications that people with excess weight may experience – for many other health problems related to excess weight we have very limited treatments (e.g. sleep apnea, urinary incontinence, fatty liver disease, osteoarthritis – just to name a few).

Indeed, if excess weight is the main cause of these problems, then treating each of these problems individually, makes far less sense than if we had a treatment that treats obesity itself – the potential benefits of this are evident in patients who undergo surgery or even in those who lose weight by other means (at least till they put the weight back on).

There is indeed no rationale why we should not have drugs to treat obesity.

Yes, weight regulation has a complex physiology – but so does blood pressure or glucose regulation – we understand the physiology and target it to lower blood pressure and control blood sugar.

Yes, weight regulation is complicated by the fact that it is also affected by environmental factors – but so are blood pressure and glucose.

And, weight regulation is further complicated by being tied into the stress and reward system – but so are blood pressure and glucose regulation.

The only difference is that blood-pressure and diabetes medications have been around for almost 100 years and it is widely accepted that these conditions need to be managed and medications are necessary to manage them.

In fact, I am not old enough to remember the days when there were no effective medications for hypertension or diabetes.

So why do we not have medications for obesity?

There are many reasons for this:

1) The inherent belief that obesity is a condition that can be overcome simply with diet and exercise (the science has long established that for most people this is nonsense.)

2) The fact that our understanding of the complex physiology of hunger, appetite, energy homeostasis and other factors is about 100 years behind our understanding of hypertension (renin was discovered in 1898) or glucose (insulin was discovered in 1921) – in contrast NPY was only discovered in 1982, leptin was discovered in 1994, adiponectin was discovered in 1996, vaspin was discovered in 2008, irisin was discovered in 2012 … and we are continuing to discover new molecules involved in fat and energy regulation every week.

3) The statuary regulatory processes for bringing new drugs to market today are several orders of magnitude more restrictive than when many of the widely used anti-hypertensive and anti-hypertensive drugs came to market.

4) While the primitive and harmful medications first launched for hypertension and diabetes in the early part of last century (e.g. mercurial diuretics, ganglion blockers or first generation sulphonylureas) are long forgotten, pharmacological disasters in anti-obesity medications (e.g. Fen-Phen) remain in recent memory.

5) Because of the barriers to bringing new anti-obesity meds to market – pharma companies would rather devote their resources to more promising areas including anti-cancer drugs, HIV drugs, or other better established indications.

6) Reimbursement systems in many countries exclude payments for obesity medications – this significantly reduces the market for these drugs – new drugs are expensive when first launched – without coverage in drug plans, most people will not be able to afford them.

7) Taking medications for obesity is still considered taking the “easy way out” – people expect you to lose and keep off your weight with diet and exercise – anything else simply proves that fat people are lazy.

Take all of this together and it is no wonder that we are still in the early pioneer days of anti-obesity medications.

But, in the end, I see no alternative to finding a pharmacological alternative to surgery – even if this may take another decade or two.

There is certainly no doubt in my mind that obesity is here to stay – the sooner we find anti-obesity drugs that are effective and safe – the better.

@DrSharma
Edmonton, AB

10 Comments

  1. Or one could address wheat addiction, fructose consumption, emotional regulation, philosophical upgrading, and dietary knowledge, and remove the cause of obesity. Those concepts separate the normal and obese people.

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  2. This topic hits home for me. I need a reasonably safe way to tackle contributory factors for weight gain. People do not think of vision problems as causing weight problems but I can not focus my eyes well together — long story but basically after more than a decade my glaucoma worsened badly in one eye then there was a follow-up bleb care complication so that eye had low IOP for too long so now have resultant retinal changes and cataract. I am learning to adjust slowly but it took me months to find that fresh ginger infused water can somewhat offset the persistent low grade nausea that feels like hunger. I would love to have an easier approach that is effective for longer but at least this helps. Meanwhile, I gained ten pounds in five months. Oh, and I am working on changing from my long-used exercise approaches and modifying them because blebs counter-indicate heavy exercise like the natural weight training I love while the vision problem can cause nausea with exercises that move me a lot unless I do them w eyes closed.

    Secondly, I have had low body temp since a very nasty respiratory virus several years ago. That has somewhat improved, and if the working hypothesis that the virus damaged my adrenals is correct then there may be more slow healing, but beyond knowing that such hypothermia increases the need for trace minerals it is an understudied field. It makes weight control difficult since I burn far fewer Calories. I had figured out lifestyle changes to help w that till the vision messed much of that up.

    Not only are meds for obesity itself needed, but more work to help w at least some contributory factors. Meanwhile, I am gaining weight and it is frustrating.

    Oh, and it would really, really help if the programs to tract calories had ALL their print sections have a large font option available. I can not use what I can not see. Frustrating…

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  3. Drugs are drugs…and there is NO drug without side effects!!
    Recently, I defined as a CRIMINAl act the approval by the FDA of the “antiobesity” drug Qsymia! This drug has, among others, a teratogenic side effect!!?? (teratogenic = causing malformations of an embryo or fetus).

    Recently a paper on a potential antiobesity drug was published, which is a shame for the scientific world! I wrote a letter to the editors, as the authors had omitted key information (initial values on the effect on food intake) in different graphs . http://www.vitasanas.ch/wp/wp-content/uploads/2012/07/Adipotide-figures-letter-to-editorobesity_scientists-web.pdf

    I would appreciate your comments!!

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  4. While we may need them, developing medications that hit only the appropriate targets without doing collateral damage is unlikely in the near future. Considering our most recent addition is a stimulant plus the side effect of anti-seizure medicine, I’m not optimistic. What happens to us when we finally find that magic pill that allows us to eat whatever we want without consequence? Will all just succumb to an endless diet of junk food and soda?

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  5. Sorry, meant to say that exercise w much motion also causes dizziness as well as worse nausea these days w the bad vision.

    I do not think that many people realize that vision problems can contribute to weight gain.

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  6. Pathetic, quit making excuses get up exercise and eat right. This is sad, far too many people are looking for any reason they can to be lazy and eat crap food.

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  7. Diet and exercise are a failure because we recommend stupid diets that put the body in a metabolic state that is almost guaranteed to fail. It is unfortunate that the US drives so much policy when it comes to what a “healthy” diet entails, when the US system has been completely overtaken by Big Food and Big Pharma interests.

    Somehow, I have a feeling we won’t be seeing a report in the US like Sweden’s recent report on the efficacy and safety of low carb, high fat diets. Yet that it what it will take to reverse the health trends in western countries.

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  8. I agree wholeheartedly. Unfortunately obesity is still stigmatized in society, quite a few of the comments here demonstrate that nicely. Although purely anecdotal, my experience has been that lifestyle modification only “works” for a small minority of people who keep up with it.

    As a recent grad I found that our obesity training was largely lacking, but I think thats mostly due to the lack of evidence for obesity management. One of the best lectures we had on this (which was a didactic 15 minutes when one lecturer finished early) went a bit into the hormones that are starting to come into play. One example he gave (unfortunately I don’t have the primary reference) looked at the levels of grehlin in a high BMI and a normal BMI group. If either group moved more than a few kilos from their “set point” weight the grehlin levels spiked, almost identically, even though a few kilo loss should have put the normal BMI group into more of a “starvation mode” than the high BMI group.

    Unfortunately weight loss is not as simple as we’ve all been taught to think it is. Traditionally I think the general majority figured “calories in must equal calories out.” My hope is that as we have further research into the hormones behind fat metabolism we will have more targets to focus interventions on.

    Another interesting point is the abuse potential. Whereas it would be much less likely that anyone would want to abuse anti-hypertensives or oral hypoglycemics, it would be much more likely that there would be a market for “anti-obesity” medications for cosmetic reasons. Of course this is not a reason to steer clear of the development of that type of medication (no one would argue for the removal of all opiates or stimulants because of abuse potential) but I think it’s something that would become a bit of an issue as these come to market.

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  9. Medical approaches do not have to be only drugs to reduce appetite or increase Caloric expenditure. Advances in brown fat and microbiome work may wind up offering some fine help.

    Dan, if your reply was to me specifically then you well illustrate the stigma that people who are obese face. From my situation specifically I can show where your assumptions are wrong, and will attempt to show where they can so often be wrong in general. MY cousin is morbidly obese; I tend to have to be careful and am — very much so. So far I have avoided obesity but several times in life have popped up into being overweight with resultant increased cholesterol and that is where I now am.

    Soooooooooo, you take someone with a genetic tendency, or genetic and behavioral tendency toward weight gain and throw in some medical problems — unavoidable for most over time — and things get very difficult very fast. For people who have stronger tendencies than mine, like my cousin, this is a very serious problem. (Lest people forget there are those genetically on the opposite end of the spectrum who also have their own suite of health related difficulties. One of my dearest friends is like that. In her case the problem is not anorexia — though people often callously accuse her of that just as many callously accuse overweight people of poor self-control and excuse making. Her problem is inherited from both sides of her family. It lets her make a good living in fashion but many in her family are short lived with high cholesterol and she rapidly gets into great risk with illnesses, so she has a very carefully managed exercise and low fat but high Calorie diet program which she carefully follows.) People have to live around their own genetics, plain and simple.

    Genetics sets limits and for each person at some point it presents challenges and limitations which may be physical, intellectual, behavioral, etc. On the other hand, even though we can not modify our core genetics we may be able to modify the genetics of our microbiome and to some extent our own epigenetics and may be able to work ourselves to our own PERSONAL optimal states — which in some aspects still will not be as good as those of people whose genetic inclinations on those aspects are better, but may naturally be better and stronger in other ways. Before I got my bleb I could do 110 pound pull downs and preacher curl 40 pound dumbbells despite being an overweight female in my sixties who never used steroids, and I have a pretty good intellect, too. We each have our own strengths as well as our own weaknesses. When people look at only one aspect of a person such as the person having an extreme of weight (high or low) and overlook the rest then that behaviorally-myopic person misses out on knowing some truly wonderful individuals.

    In my case I am having to change my long term exercise approach because people who have had large blebs created to combat glaucoma — even without a surgical complication — have to limit heavy exercise and go to more and shorter bouts of lighter exercise to avoid having the bleb develop a leak. Basically, imagine the problems if your eyeball itself leaked and became hypotonic (too low pressure like a deflated basketball) — best avoided, right? In addition, when eyes can not focus together both low grade nausea that is hard to distinguish from strong hunger and dizziness w too much motion (including increases in motion sickness) are COMMON problems. With an aging population many more people with such difficulties will be seen. Do not accuse me of not exercising. Despite being a woman in my sixties I still have larger and firmer upper arms than most young men, but having to limit and alter my exercise program to avoid destroying what remains of that eye is actually not as easy as you might imagine.

    Nor is burning what my physician estimates to be 10% fewer calories easy to work around, especially now that I can no longer see my diet tracking program clearly since rather than have a full screen zoom feature they only allow enlargement in the tally section but not in the sections to look up and enter the items. This also is a problem that the makers of such programs need to address for the aging population.

    In my cousin’s case on top of her obesity (which is found in each side of her family) — with aging she has developed endocrinological problems that also contribute. She has a truly tough combination. If you listen to people with health problems there are so many combinations which people are trying to find a way to work around, and those combinations are REAL, but if we can come up with what we need then we can adjust despite them, and advances in treating and preventing obesity and contributory factors for obesity can offer people OPTIONS. There are options for so many things, but medical problems that carry stigmas and assumptions tend to have fewer.

    BTW, it would not be a surprise if my diet is healthier than yours, with 5 to 9 vegetable or fruit servings per day, whole grains, small servings of flesh foods with most of that seafood or white poultry, fat-free dairy, olive or peanut oil, a small serving of tree nuts three times a week, and days that are all vegetarian except for FF milk or FF yogurt. Having to adjust for the reduced burning of calories, though, means I need to track so not being able to see the tracking program is really hard on me. See if someone can help you fake what it is like to have severe myopia and typical presbiopia with glaucoma in one eye and the other eye having advanced glaucoma, large bleb, folded retina, bad astigmatism, cataract, and bad glare problem. Then try using a program with small font. If you can even manage just part of that, for example by putting an eye gel like Refresh PM liberally into your eyes, you will get a bit of feeling for it. Like I said, especially with the population aging those companies need to work in fixes for those who can not see clearly.

    While it is true that some people make excuses, it must be acknowledged that what may feel like excuses to people who lack those same problems are often enough hurtles that are natural to another’s biology. Some who are accused of not taking precautions and adjusting behavior actually adjust behavior in healthy ways to a greater degree than many without problems.

    The advances I am strongly hoping for to help with overweight are these:
    1. Ways to safely increase brown fat percentages, or at least manage to get more beige fat given that each burns calories instead of accumulating them.
    2. Further increases in knowledge on how to manage the microbiome in terms of both diversity and having more of the types of flora that reduce inflammation and fewer of those which increase it.
    3. Safe ways to reduce nausea
    4. More knowledge on hypothermia that is not caused by the thyroid
    5. Aids such as online diet programs being made more accessible for the limitations that go with an aging population

    If assumptions caused by stigmatizing can be reduced then that could help, too.

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  10. I would add that the issue has NEVER been about weight loss (most people can do that), it’s about weight-loss maintenance and pharmaceuticals to address that issue aren’t even being created because they lack a regulatory avenue toward approval. As far as the powers that be are concerned, once a person has lost weight he or she is “cured” of obesity. He or she may be thinner but certainly not cured of anything. That person suddenly has a endocrine profile that is VERY challenging to manage. Macronutrient adjustment (but not nutritional zealotry) as well as regular, intense exercise, can be helpful, but doesn’t completely solve the issue, and so few people (even MDs) even acknowledge that the issue weight-loss maintenance exists, moreover that it is the central issue not the loss itself. Arrrrgh!

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