Wednesday, February 2, 2011

FDA Rejects Contrave for Obesity--Big Mistake

As you can read from various sources, including the NY Times, the LA Times, and the Washington Post, the FDA has rejected another anti-obesity drug, Contrave, because of concerns that it might cause heart attacks in patients who take it for years.

FDA's excessive caution was motivated by its experience having been burned by the Fen-Phen fiasco. This was a weight loss drug widely prescribed in the 90s that was pulled from the market after studies showed it caused fatal lung and heart valve problems. 

This new drug, however, is a combination of two medications that have already been widely prescribed and are fairly safe: Wellbutrin and naltrexone. Psychiatrists are familiar with both of them. We prescribe Wellbutrin for depression and smoking cessation, (and off-label for weight loss, for which it has shown efficacy as a stand alone), and we prescribe naltrexone for alcoholism.

As you can see from information published on Clinicaltrials.gov, Contrave is simply a combination of Wellbutrin 400 mg with Naltrexone at a couple of different doses, 48 mg and 16 mg. Clinical trials showed that Contrave helped 50% of obese patients lose 5% of their body weight, while only 10% of patients on placebo lost that much weight. The FDA's advisory panel voted to recommend approval, but the FDA demurred, saying that the company, Orexigen, will have to conduct a huge placebo-controlled long term study to make sure the drug doesn't cause heart attacks (one of Wellbutrin's well-known side effects is a slight increase in pulse and blood pressure, although there were no heart attacks in the Contrave clincial trials).

In my opinion, the FDA made the wrong decision. Obesity is a public health catastrophe, and Contrave's approval would have been predicated on conducting post-marketing safety studies anyway. The good news is that patients can ask doctors to prescribe them the constituents of Contrave, both of which are available in generic form--burpropion and naltrexone. Presumably, this generic combination will be much cheaper than Contrave's pricing anyway!

34 comments:

moviedoc said...

I agree. Fixed-dose combos are rarely a good idea, and bupropion XL generic comes in 450mg, naltrexone in 50, pretty close to the rejected preparation. Keeping them separate also means a patient who needs opiate analgesia post-op or post injury can continue to beneifit from the bupropion during temporary discontinuation of the naltrexone.

pacificpsych said...

I'm thinking this post is some kind of joke. Why would you suddenly post a pro new-mostly-useless-drug, anti-caution post? It almost sounds as though you're paid by the manufacturers of Contrave, which of course you're not. There must be some other purpose here... Maybe you're trying to point out something about the problems in non-psychiatric drugs...to see if your post will elicit objections, or if those are only reserved for psychiatry...

Daniel Carlat, M.D. said...

Actually, I'm quite serious about this post. I think Contrave should have been approved. Combining Wellbutrin and naltrexone was not something the average doctor would have ever thought of for an obesity treatment, so this counts as an uncommon example in which a company had a bright and non-trivial idea for a combination of two existing products. As psychiatrists, we see obese patients all the time, and the more I have to offer them, the better.

moviedoc said...

I'm glad to hear I didn't fall for a joke, but the fact that the average doc might not have thought of it implies we need more effective dissemination of such info, not a new commercial product. Or are you thinking the inevitable TV ads might be a good way to get us all up to speed?

pj1280 said...

I have to agree with pacificpsych and moviedoc.

It's a gimmick, Dr Carlat, pure and simple. Why do you think that "combining Wellbutrin and naltrexone is not something the average doctor would have thought of"? It's because the data (about two drugs that are already available and have been for years!) have been hidden from those doctors (and the public) for the purposes of financial gain for Orexigen's shareholders.

aek said...

Different point of view here. Although this wasn't the basis of the rejection, I'm glad that it wasn't approved because fundamentally, nutrition and eating are not medical issues. Nutrition should not be medicalized except as a true last resort.

I'd much favor a public health/primary care/corporate approach to weight/metabolic derangement by making processed food-like products higher priced/taxed - ergo more inaccessible, subsidizing fruit, vegetable and nut growers, eliminating the big three ag subsidies (wheat, soy, corn) and heavily marketing a no added sugar diet (making fruit the sole source of dietary sugar which allows hunger and appetite to self regulate, and which mostly eliminates blood glucose peaks and valleys). Finally, the new USDA guidelines do address upping fatty fish intake, but along with increasing n3 fatty acids, the consumption of n6 fatty acids must be dramatically decreased. That means minimal to no corn, soy and other seed oils.

Given that studies are providing evidence of much higher levels of gluten sensitivities in people with ASDs and their families, cholesterol derangements in people dx with schizophrenia, bipolar and MDD, and fairly strong possibly bidirectional correlations between CVD and depression, shouldn't addressing diet play a more prominent role in treatment?

Eating is enmeshed in culture, society and lifestyle. Optimal lifelong eating habits and nutritional patterns can certainly be modeled, taught, encouraged and maintained.

We continue to focus on weight loss instead of looking at permanently correcting eating patterns and allowing for weight regulation to occur as one of the results, along with metabolic re-regulation, minimizing chronic inflammation and improving immune status.

One of your colleagues, Emily Deans, is a Harvard educated psychiatrist who is now blogging about psychiatry and nutrition at Evolutionary Psychiatry (link at my name). Id' be interested in your impression.

SteveM said...

Danny,

Shouldn't all weight management programs also have diet and exercise components? A weight reduction clinical trial for patients with "Uncomplicated Obesity" that is not holistically designed doesn't make sense because it avoids life-style management all together.

So what would be the relative weight loss results if the study cohorts were also placed on exercise and proper nutrition programs as part of the study design? If I'm the FDA, I'd tell Orexigen to do that kind of integrated study and get back to us.

Moreover, a 5% weight reduction success target enabled by a no doubt expensive drug formulation seems pretty modest to me. I.e., couple hundred bucks a month for Contrave in perpetuity for maintaining a 15-25 pound differential? For a 300 to 500 pound person? Without the lifestyle changes?

Meh...

Daniel Carlat, M.D. said...

All good points here.

I'm all for diet and exercise as preferred alternatives, and I also understand that simply putting two existing meds together does not represent the pinnacle of pharmaceutical science. But 5% weight loss is better than nothing, and this in itself will reduce mortality from heart disease in a significant number of people.

More broadly, just because pharma has plenty of ploys up its sleeve does not mean that we should resist efforts to market incremental improvements--as long as the marketing is done ethically and without the use commercial cme and hired guns. In this case, we see a marginally effective medication for a catastrophic public health problem. Why not approve it with the stipulation that the company do its post-marketing safety studies?

moviedoc said...

Yet another angle: 3-4 years ago Hythiam started promoting their patented Prometa protocol which calls for flumazenil + hydroxyzine + gabapentin to treat meth, ethoh, and cocaine addiction. All 3 drugs were off-patent like bupropion and naltrexone. Why didn't this company just patent the use of the combination and avoid the need for FDA approval? Or maybe they did get a patent and will sue any of us who try to use it.

SteveM said...

Re: Danny, "All good points here."

The larger systemic issue is the benefit/cost ratio of these reformulations. My favorite analogy is the Lovaza scam:

http://heartscanblog.blogspot.com/2008/12/lovaza-rip-off.html

I suppose you could come with an argument for Lovaza's marginal utility over fish oil caps. But does it actually make sense to prescribe?

Contrave is Lovaza but for a different disorder. Prescribing it over a generic mix would seem to be another pathological contribution to an economically out of control health care system. Maybe FDA considered that without letting on. But if they did, it would not bother me.

In the end, Big Pharma wields the Big Media Club even when the message defies common sense.

pacificpsych said...

If we're seriously going to debate this pill...

If someone weighs 200 pounds and they wanted to lose 10 pounds, they could do so by the amazing miracle cure of walking one hour a day. If they walked at a moderate pace of 3 MPH, they'd burn according to one calculator over 400 calories. Let's say just 300.

Twelve days like that, assuming intake = caloric need to remain at same weight, they'll have lost one pound. One hundred and twenty days, there go the 10 pounds.

One year, thirty pounds.

Cost = one pair of good walking shoes, one hat, sunscreen. And some willpower. Hmmm.....

Dr John said...

Dr Carlat, can you present some data to support your contention that a 5% wt reduction by any means or one driven by meds rather than exercise and diet reduces mortality? I would challenge this contention but maybe I am wrong. I understand your desperation to do anything to tackle the problem of obesity but this would seem to be a poor investment.

As to aek's comments, I share your sentiment on the drug's failure to be approved but lack your enthusiasm for the nanny state and subsidies of any kind. People tend to be pretty good at finding enjoyment in things that are bad for them regardless of big brothers attempts at punishing them economically.Tax peoples favorite sin and they just find a different flavor of sin.

Joel Hassman, MD said...

Very, dangerous, path, you are taking here. Supporting the use of antidepressant and opiate antagonists for weight loss is only playing in the hands of pharma, just trying to get more indications for meds and just further patent access.

Why not just use Topamax. And, while the risk for seizure with buproprion has been low, using a 400mg dose as a first dose seems rather risky to me.

All in all, I find this post baffling at the very least.

Anonymous said...

I agree with pacificpsych:

TELL THEM TO GO TO THE GYM!

QoS said...

Lately I've seen some clinicians and researchers approach obesity as an eating disorder in terms of offering cognitive and behavioural interventions, and this seems to work.

Given the scale of the problem, I agree that there should be some public health initiatives in place but good luck with the regulation of junk food, additives, high-fructose corn syrup, etc: the food industry is at least as gigantic as pharma. In my corner of the world, a publicly-funded phone helpline has just opened up for food and exercise coaching - hopefully this yields some results, because our obesity problem is quickly approaching that of the US in scale.

5% loss seems modest, considering that this is roughly the same number you get with a low-fat diet and/or mild daily exercise while keeping your intake the same, plus taking this medication alone, as pointed out above, will not necessarily lead to lifestyle changes.

moviedoc said...

I thought diet + exercise were pretty much acknowledged to flop. I think it's more likely the pill(s) vs. bariatric surgery. How is that combo supposed to work, anyway? BTW: old-fashioned venlafaxine IR works for some.

Becky Murphy said...

I for one truly appreciate the professionals who are addressing the RESPONSIBLE solution: Diet and Exercise Obesity is caused, except for RARE cases of underlying pathology, by unhealthy diets: they eat the WRONG amounts of food, and unhealthy, i.e. fried, and processed foods diets lacking whole grains and fruits and vegetables, and fail to exercise! A pill of any kind is not going to fix the underlying cause of their obesity...Lifestyle and BAD choices. Drugs are a way to avoid responsibility for how one's choices have everything to do with the person who is morbidly obese. How is it justifiable to medicate rather than address the real issue?

I have been overweight and unhealthy much of my life; and it was not until I ate better and moved my ass that I became healthier and happier. I now wear the same size clothes I wore as a teenager, and am the healthiest I have been my entire adult life. Thank God, I did not resort to a quick fix, like phen-fen, or any other "medical" solution to my lifestyle issues...

Anonymous said...

they could do so by the amazing miracle cure of walking one hour a day.""


THANK YOU! (Daily walking is free too except for the cost of the shoes.) And what about the benefits of exercise on muscle tone, cardiovascular health, mood and cognitive function, and Growth Hormone release?

Asslete said...

In skilled and cautious hands, a hammer and chisel can shape beauty out of boulders. But in the hands of the masses, that same hammer and chisel create little more than gravel and dust. Contrave, like the psych-meds we discuss here, had the potential to help, when used sparingly and skillfully. But the FDA rightfully recognized that we physicians as a whole, and the minute-rice masses we serve, could not be trusted with this particular hammer and chisel.

Contrave-The Good:

Across 3475 patients exposed, and 2313 patient years of exposure, Contrave consistently demonstrated clinically meaningful weight loss. And I do emphasize “clinically meaningful” to Dr. John contention. Across all studies, patients on Contrave lost an average of 5-9% of their body weight. They dropped A1C by .6%. They reduced CRP by 7-20%. They lost 11% body fat compared to 4% for placebo…and they lost 15% visceral body fat compared to 5% placebo.

Those are some damn decent numbers…and if you look at the work from Avenell, Eliat-Adar, or the US Cancer Prevention Study…you could argue those are life-saving numbers.

Contrave-The Bad:

Those were 3475 potentially fortunate patients to have been placed on Contrave. About half of them lost 5% or more of their body weight. But what about the rest…the 12-20% who lost no weight and may have actually gained weight? Would it bother you to know that in the one study that included “intensive lifestyle intervention” the average placebo percent weight loss was quite close to the weight loss achieved in other studies of Contrave users who did not have meaningful lifestyle intervention. It would appear that good old fashion, “eat less, exercise more” works quite well…for those willing to do it. Would it bother you to know that the majority of patients studied were female, yet it is men who are at the greatest risk for CVD from obesity…and CV risk seemingly from Contrave based on the Major CV events reported to the FDA? Or how about the relative risk of ischemic heart disease at 1.3 for Contrave over placebo?

Contrave-The Ugly

Getting back to those 3475 patients…for the most part, they were obese but not too ill. The list of excluding illnesses, lab values, and medications is larger than…(insert inappropriate fat joke here). They were so exclusive, that in my mind, there remains a great unknown for how Contrave would work amongst actual “real people with real illness” or for that matter, how would Contrave work for the millions of mildly overweight people who would no doubt be lined-up around the block of the nearest Medi-fast weight loss center just to lose 5 pounds before bikini season.

I say it is best to let Contrave’s carcass lay decomposing at the feet of the FDA.

For those willing to study the science…for those willing to be selective…for those willing to be cautious…it’s mighty easy to RX generic bupropion sr and naltrexone together. I use this combo with reasonably good results. But like most psychiatrist, I convince myself that I know how to wield my hammer and chisel, and select the right boulder…often ignoring the pile of gravel and dust that gathers on my shoes.

Anonymous said...

Movie Doc,

Perhaps diet and exercise have flopped because many medical professionals are having people do the same things that don't work.

For example, this study show that a Paleolithic diet had success over the typical low fat, high carb ADA diet

http://www.ncbi.nlm.nih.gov/pubmed/19604407

According to Chris Kresser, who owns the Healthy Skeptic, http://thehealthyskeptic.org/the-top-3-dietary-causes-of-obesity-diabetes:

* Reduced HbA1c more than the diabetes diet (a measure of average blood glucose)
* Reduced weight, BMI and waist circumference more than the diabetes diet
* Lowered blood pressure more than the diabetes diet
* Reduced triglycerides more than the diabetes diet
* Increased HDL more than the diabetes diet

At the end of the trial, 8 out of 13 patents still had diabetic blood glucose levels. However, in this study the patients had well-established diabetes for an average of 9 years. Over time diabetes progresses to beta cell destruction, which reduces insulin output. Once this point has been reached, dietary changes can be helpful but cannot completely reverse diabetes.

Regarding exercise, Mr. Kresser, makes the point on his site, http://thehealthyskeptic.org/how-to-lose-weight-and-prevent-diabetes-in-6-minutes-a-week, that while low intensity cardio is beneficial health wise, it doesn't contribute to weight loss. He provides links to studies showing that High-intensity intermittent training may work best.

Obviously, personal experience doesn't make for a study but that definitely has been true in my case.

Anyway, I realize this is not a one size fits all solution. And obesity can get to the point where only surgery will work.

But my point is that obviously, with the huge increase in obesity and diabetes, the same old, same old solutions are not working.

Dr. Deans, you have a great site by the way. You might want to look at the Healthy Skeptic Site as it sounds like your philosophies are quite similar.

AA

Dr John said...

Asslete, that was a great post. Those numbers are cosmetically significant and maybe even "clinically meaningful" although I am not sure what that term means here. What I want to know is has anyone ever shown that reducing an obese persons body wt by 5% results in a significant reduction in mortality or disease related morbidity of any kind i.e. stroke, MI ect ect?

If no one has I like other posters really question the approach of giving costly meds for marginal benefit.

I think Becky Murphy hit a home run. I am a pragmatist and will do whatever works but like her I don't think anything really works but eating less and moving your ass a lot more. That is why this is such a difficult problem to tackle.

We have evolved in such a way as to be good at storing excess calories. A stable food supply has turned what was once a genetic asset to a modern day liability.

moviedoc said...

Apparently a lot of psychiatrists (not me) prescribe metformin to counteract weight gain associated with psychotropics. How about a head-to-head between metformin and bupropion/naltrexone? And Dr John, who's to say the latter won't work by making you want to eat less and move your ass more?

Asslete said...

Dr. John

There are countless studies that have demonstrated both decreased morbidity and decreased mortality with even modest intentional weight loss. This is one is perhaps most well known:

http://care.diabetesjournals.org/content/23/10/1499.short

But with that said...there are also several studies that suggest weight loss makes no difference. Here is one such study:

http://www.ncbi.nlm.nih.gov/pubmed/15001038

Sure "eat less exercise more" makes the most sense, much like "let's talk about your horrible marriage, job, child abuse before we put you on Prozac" makes the most sense. But common sense is seldom common. And so both Docs and Patients seek out more quick fixes that may or may not be more harmful than helpful.

I never sleep well at night doing this job...but I think I'd be worried if I did.

Joseph P Arpaia, MD said...

I do a lot of work with patients who have behavioral issues, weight control being one of them. I have been adding the combination of Wellbutrin and Naltrexone to the behavioral advice for a couple of years.

Two points

1) The dosing is not "cookie-cutter". I have patients who do really well with very small amounts of naltrexone sometimes obtained at a compounding pharmacy. The ratio of Wellbutrin and naltrexone also varies widely. So a combination pill is just another patent extender, and reduces the ability of the clinician to adjust dosing.

2) I have used naltrexone a lot because I treat behavioral disorders such as addiction, eating disorders, ... . Naltrexone can make a big difference, in the context of a motivated patient who is working hard in a behavioral program. I have not seen it do anything long-term to change people's behavior when they were not motivated or in the absence of a behavioral program.

aek said...

I'm pleased to see that AA referenced a Paleo diet.

In my own n=1 of being overweight from childhood on, but always having been active, I stumbled onto a Paleo type diet when I trialed a gluten-free, no added sugar diet for a month after getting a big jolt from pre-op labs and a medication-related fast weight gain. I discovered that I craved added sugar foods, and it took a full month before my senses of taste and smell reset and inappropriate hunger and food cravings went away. I did not count calories, but ate only whole foods, no seed oils, started taking omega 3 fatty acids while upping fatty seafood, and then learned that I needed to bring the omega 3 to omega 6 fatty acids to a 1:1 ratio. Kept a food/nutrient diary until me new eating patterns were well established and optimized and only supplement what I can't get via food (vitamin D, B12 - deficiency brought on by prescribing a PPI as coverage for NSAIDs). My body fat and BMI dropped to within the lower end of normal, I have no more food cravings, and I haven't regained weight. My activity increased only with a reduction in back and large joint pain.

Eating a Paleo style diet allows me to eat a rich diversity of foods in limitless cultural and social ways. But as I revisited the nutrition literature, I discovered just how wrong conventional wisdom (in medicine, nursing and allied health professions) is.

Along the way, my lipid profile and metabolic profile became optimal (a cardiologist told me that I'd live forever) from starting out with several risk factors for metabolic syndrome. I'm now on no meds, and at this juncture, am not deemed at risk for any chronic diseases other than osteoarthritis, which was in progress from early adulthood.

You do recall that cholesterol is essential to brain structure and function, yes? (grin)

As I've been reading scientists who investigate and report on Paleo nutrition, I'm learning that my experience is pretty close to the norm.

None of the physicians I saw ever expressed interest in my diet, asked me what I did, advised dietary or activity interventions, or offered anything other than medication.

The kicker: I used to teach undergraduate basic nutrition to allied health and nursing students. And regarding clinical nursing, what I know now about nutrition makes me regretful regarding what I never even knew to offer to patients to enhance theirs.

But I do know this: eating is enmeshed in daily life. Medications, enteral feeding, gastric surgeries, etc. don't address the fundamental, elemental role of eating. And that's at the root of obesity, diabetes, CV disease, and other metabolic and inflammatory derangements.

Anonymous said...

I assume you are well aware that companies whose drug approvals have been granted with the requirement that they conduct post-marketing safety studies have, for the most part, not conducted those studies and have suffered no ramifications or penalties for not living up to their end of the bargain. Since I assume you know this, I wonder why you would suggest that the manufacturer of this particular drug would be any different.

I also find it curious that you are so blindly accepting of a drug just because you happen to prescribe its individual components. Perhaps rather than thinking, "We prescribe this all the time... it's obviously safe," you might explore the other side of that coin --> "We prescribe this all the time. Maybe we shouldn't. Maybe we should examine our practices more closely. Maybe we should examine the drug company-funded studies of the drugs we prescribe more closely. Maybe the FDA sees something we don't see."

Lately, you seem eager to rip apart the claims of others who write books, etc., but you do not apply the same critical eye and detailed references to support your argument when the topic is your own view of the way things are/should be. You seem eager to provide citations/references to back up your arguments as you tear others to shreds, but I rarely see citations or literature references given when you are making the "trust me, I'm a psychiatrist... and because I prescribe it/do it, it is safe/good" argument I am seeing too much on this blog of late. I am very disappointed.

Anonymous said...

Becky Murphy said:
"A pill of any kind is not going to fix the underlying cause of their obesity...Lifestyle and BAD choices."

//

You just nailed it. This is why this post rubbed me the wrong way. It's such a typical psychiatric response to a problem - throw another pill at it and pretend that the pill doesn't just cover up the symptoms. People don't get better that way, Dr. Carlat. They may feel better, but they don't GET better.

What happens when they stop the drug and gain all of the weight back, plus some additional pounds? Or are you suggesting they should take this drug for the rest of their lives? Either way, you're not treating the problem, you're treating the symptoms. Because it's faster and more lucrative to treat symptoms, as you acknowledge in your book.

Alex Pirie said...

What? Another drug or combination of drugs or re-combination of drugs - big pharma working overtime to improve our health? Becky Murphy and Dr. John said it all much better. So I'll just add: NIH R&D = $28.5 billion, CDC and FDA combined = $600 million. Or, welcome to America (land of embarrassing health indicators) where an ounce of preventative funding makes the pharmaceutical stockholders cringe and run for the nearest lobbyist. The running does do wonders for their metabolic balance, though, so maybe there is some good in here after all...

Anonymous said...

Interestingly, on the blog entry on AOL by Dr. Carlat, http://www.aolhealth.com/2010/12/07/how-to-get-the-truth-out-of-your-psychiatrist/, he talks about a study that said that if patients asks psychiatrist what type of treatment they would chose for themselves. they would take a wait and see attitude.

I am curious in light of that study if patients are offered the same opportunity. For example, instead of automatically offering Wellbutrin to an obese patient, does Dr. Carlat take that approach with this person, particularly if the person is otherwise stable healthwise?

Asslete, am I interpreting the studies correctly that the ones for Contrave ran about 6 months? That is certainly better than the typical 8 drug week studies but still, that is not nearly enough time to prove whether a drug works or not.

AA

John, MD said...

I am currently a public health candidate (MPH) and an orthopedic surgeon. I have serious trouble believing that obesity is a true epidemic at all.

For someone who is sincerely against the abuse of prescription medications, perhaps you should become more aware of the abuse of the "obesity epidemic." Somehow, I think that some of the commentators here and perhaps yourself have heard of this before. Its a shame then that you are so concerned with obesity.

There is no causal linkage between obesity and heart disease. Obviously heart disease is a multi-system problem and discovering underlying causes can be difficult because they may be masked by multiple factors-epigenetic factors of the environment, exercise, diet, etc as well as genetic predisposition, etc.

However, being fat alone should be the cause for concern and certainly losing weight does not guarantee no onset of CVD.

gewisn said...

i suppose we shouldn't be surprised at the theme of the posters in this anti-pharma blog.
But on another note, I have to admit naivete. I don't know the science showing that weight-loss through medication gets the same health benefits as weight loss through diet and exercise. Are they the same? I'm sure some assume "yes" and some assume "no," but I don't know what the science shows. Can anyone direct me to such studies?

Also, is there any way to "convince" (or force) insurance companies to give patients a choice between benefits of paying for a medication or paying for attendance at a gym? Suppose an insurance company gave you back $5 for every 30 min session on a cardio machine or exercise class at a gym, up to $40/week? Its amazing what you can get people to do for CASH. This principle has filled the pages of psychology journals for generations, since "psychology" is largely the science of paying college sophomores to do ridiculous things for cash.

Anonymous said...

Yes, Gewisn, it is indeed amazing what people will do for cash. Psychiatry and the rest of medicine are learning this lesson over and over again with the new revelations and exposés of each passing month.

Anonymous said...

To the poster who wrote there is no causal link between obesity and heart disease I would strongly disagree. Obesity is an independent risk factor for cardiovascular disease. In combination with other independent risk factors it is associated with insulin resistance, diabetes and dislipdemias. I'm not sure what they are teaching you in your MPH program.

Anonymous said...

To those who so strongly believe that obesity causes the world's problems, remember that obesity is a risk factor. I am aware of no science that states it is the CAUSE of heart disease, diabetes, etc. If anything, isn't it possible that obesity is another symptom? Some studies show that some diabetics gain the weight AFTER diabetes has begun to develop.

This obesity crisis is concerning, in that people are focusing on "fatness" rather than on health. They are not the same thing. Shame on any doctors/nutritionists/psychiatrists who are looking for a way to blame the patient. If they are fat and healthy, leave them alone. If they are fat and sick, treat the sickness. Encourage EVERYONE to be active, not just fat people. Don't do harm to fat people by treating for "diseases" like obesity that could merely be a symptom. You don't die of being fat (unless you are at the point of having crushed airways or starve to death because you cannot move to feed yourself), you die of the disease that came along with the fatness (i.e. stroke, heart attack). Common sense, people. Don't medicalize a risk factor by calling it a disease in its own right.

Also, Linda Bacon has done some great work collecting medical studies on weight loss/health. Weight loss does not usually lead to long-term health by itself; the lifestyle change (with or without weight loss) does.