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5 Years Later: Surgery Still Beats Conventional Treatment for Type 2 Diabetes

sharma-obesity-surgery2Readers will recall previous posts on the STAMPEDE trial, an ongoing trial of 150 patients who had type 2 diabetes and a BMI of 27 to 43 who were randomly assigned to receive intensive medical therapy alone or intensive medical therapy plus Roux-en-Y gastric bypass or sleeve gastrectomy.

Now the 5 year results of this trial have been published in the New England Journal of Medicine.

Of the 150 patients who underwent randomization, 1 patient in the medical-therapy group died during the 5-year follow-up period (from myocardial infarction during year 4) and 1 patient in the sleeve-gastrectomy group had a stroke; 134 of the remaining 149 patients (90%) completed 5 years of follow-up. One patient in the medical-therapy group, underwent gastric bypass during year 3, owing to failure of the medical treatment. One patient in the sleeve-gastrectomy group underwent gastric bypass during year 4 for the treatment of a gastric fistula.

At 5 years, the criterion for the primary end point (Hba1c <6% without the use of anti-diabetic mediations) was met by 2 of 38 patients (5%) who received medical therapy alone, as compared with 14 of 49 patients (29%) who underwent gastric bypass and 11 of 47 patients (23%) who underwent sleeve gastrectomy.

At 5 years, changes from baseline observed in the gastric-bypass and sleeve-gastrectomy groups were superior to the changes seen in the medical-therapy group with respect to body weight (−23%, −19%, and −5% in the gastric-bypass, sleeve-gastrectomy, and medical-therapy groups, respectively), triglyceride level (−40%, −29%, and −8%), high-density lipoprotein cholesterol level (32%, 30%, and 7%), use of insulin (−35%, −34%, and −13%), and quality-of-life measures.

Excessive weight gain was observed in 19% of the patients in the medical-therapy group and in no patients in either surgical group.

No major late surgical complications were reported except for the one reoperation mentioned above.

From these findings the author conclude that,

“…bariatric surgery was superior to intensive medical therapy in terms of glycemic control, weight reduction, medication reduction, improvement in lipid levels, and quality of life. Patients who underwent gastric bypass or sleeve gastrectomy were significantly more likely to achieve and maintain a glycated hemoglobin level of 6.0% or less, with or without medications, than were those who received intensive medical therapy alone…The surgically treated patients had superior glycemic control throughout the 5-year period while also using fewer diabetes medications, including insulin. More than 88% of the surgical patients had glycemic control that was considered to be very good to acceptable (average glycated hemoglobin level of 7.0%), without the use of insulin. A majority of the surgical patients who achieved a glycated hemoglobin level of 6.0% or less reached that target without the use of diabetes medications, whereas none of the patients in the medical-therapy group reached that target without the use of diabetes medications.”

No doubt this study supports the notion of long-term benefits of bariatric surgery (even in people with BMI in the 27-34 range) compared to intensive medical treatment alone. Clearly, this should be a treatment that may be considered for patients with type 2 diabetes, who struggle with glycemic control.

@DrSharma
Edmonton, AB

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Scalable Obesity Treatments: Time For Pharma To Step Up

time spiralIn my two previous posts (here and here), I have discussed the urgent need for obesity treatments that are scalable to the size of the problem. I explained why neither “lifestyle” nor surgery are scalable to the millions of Canadians who would stand to benefit from obesity treatments.

No doubt, not everyone with a BMI over 30 needs treatment. As I also discussed, we should target treatments (especially with anti-obesity medications) to those who are actually experiencing an obesity related impairment in health, especially those with comorbidities that are not well controlled and who are otherwise good candidates for treatment.

As I calculated, this reduces the number of Canadians that would really need to be treated for obesity from about 7,000,000 to perhaps 1,250,000 – roughly half the number of Canadians currently living with diabetes, a chronic disease that is routinely managed with medical treatments.

 

Many of these would no doubt stand to benefit from surgical treatments, but at the current rate of about 10,000 surgeries a year (a number that is unlikely to dramatically increase in the foreseeable future), I see no alternative than the use of anti-obesity medications.

This is where we have a real problem.

While for any patient with diabetes or hypertension who walks through my door, I have over 100 possible prescription medications to pick from, including an almost limitless number of possible combinations, for obesity I have almost nothing.

The two only prescription medications for obesity currently approved in Canada are orlistat and liraglutide. The former is moderately effective but is handicapped by unpleasant side effects. The latter, is an injectable hormone-analogue, where access is limited by cost (in Canada about $15 a day).

Obviously, not everyone will tolerate or respond to either of these medications. This is not unexpected. In fact this is the very reason that we have so many different classes of drugs for the treatment of other chronic diseases like hypertension or diabetes – what works for one patient does not work (or is not tolerated) by another.

So why do we not have more therapeutic options for obesity treatment?

The only answer that springs to mind is that Big Pharma is not putting the same dedication and resources behind developing anti-obesity drugs compared to what they are pouring into other indication areas.

Thus, while Big Pharma is busy developing and appears to be launching new drugs for diabetes almost every other month, nothing remotely comparable is happening in the obesity space.

thus, virtually every multinational pharmaceutical company has active development programs for diabetes.

In contrast, almost no multinational pharmaceutical company has an active development program for obesity worth speaking of.

The only reason that I can think of why a Novartis, Pfizer, Roche, Sanofi, Merck or any of the other major pharmaceutical companies are not investing in finding, developing, and bringing new anti-obesity drugs to market to fill this gaping therapeutic gap, is that they do not expect to make money with anti-obesity drugs.

This is largely because, as we have seen with past introductions of anti-obesity drugs, medications for obesity are seldom covered by pharma benefit plans or public formularies, making access to these drugs for a relevant number of patients difficult.

This lack of coverage of obesity drugs has little to do with the actual cost of new medications. In fact, even the currently most expensive anti-obesity drug in Canada works out to only around $5,000 a year – a sum that drug benefit plans routinely spend on managing patients with diabetes year after year after year.

So if it is not the cost of treating obesity that is prohibitive, why do most people who would stand to benefit from obesity treatments (and remember, we are only talking about half as many people who are currently being treated for diabetes) not have access to obesity treatments?

My guess is that this has a lot to do with the fact that obesity (in contrast to hypertension or diabetes), is still not widely seen as a chronic disease requiring treatment in its own right.

For one, most doctors have never prescribed a medication for obesity – they were simply never trained to do so.

In addition, employers (who generally pay for their employee benefit plans) are offered the option of opting out of covering obesity treatments (drugs or otherwise) – unfortunately, most employers do.

Of course, I understand that prescriptions medications (even after their regulatory approval and meeting the relevant efficacy and safety standards) should only be covered if they promise real health benefits, which of course have to be demonstrated in clinical trials.

But we will never have those new medications or the trials that prove their efficacy, if companies believe that despite all efforts, their medications will not recoup the investments or make profits for their shareholders.

This is where policy makers need to step in.

For one, governments could consider providing significant incentives (e.g. tax breaks?) to Big Pharma to devote resources specifically towards developing new medications for obesity.

Secondly, governments must streamline the approval process for new obesity medications in a way that will ensure that these treatments become available to those who stand to benefit (and I don’t mean anyone who is hoping to lose a couple of pounds to fit into their wedding dress – I mean people with at least Edmonton Stage 2 obesity, especially those with poorly controlled obesity related health problems).

Thirdly, employers and benefit plans should no longer have the option of opting out of paying for obesity treatments (in the same manner that they cannot chose to simply not cover diabetes or hypertension or any other chronic disease).

I believe that if these measures were implemented, at least some of the big pharmaceutical companies will reassess their position on developing safe and effective anti-obesity medications.

With more pharmacological options (and more competition in the market place), I see no reason why the standard for obesity care cannot be on par with what is currently routinely offered for patients with diabetes, hypertension or most other chronic diseases.

Without these policy changes, I fear that we will never have obesity treatments that are scalable to address the size of the problem.

The time for policy makers to act is now!

@DrSharma
Edmonton, AB

Post script: I harbour no illusion that any change in policy in Canada alone will make any difference to Big Pharma – after all, the Canadian pharma sales are only about 2% of the global market. Rather, it would take a consortium of countries, including the biggest markets, to make a joint decision regarding any such policies. Sadly, I believe that the  chances for this in the current political climate are rather remote – but, then again, we can always hope…

 

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Scalability of Obesity Treatments: Need To Target

bariatric patient in bedYesterday, I discussed the desperate need for scalable obesity treatments.

I pointed out that neither behavioural nor surgical interventions are readily scalable to provide long-term obesity treatments to the over 7,000,000 Canadians currently considered to have obesity.

I also noted that, like for other chronic diseases, only medical treatments with anti-obesity medications have the potential for scalability in the millions – we do this regularly for the millions of people living with diabetes, hypertension, heart disease, or any of the other common chronic diseases affecting Canadians.

Nevertheless, before we discuss what it would take to scale up medical treatments, let us take a look at whether all 7,000,000 affected Canadians really need obesity treatment.

Let us first note that the number 7,000,000 refers to Canadians with a BMI over 30. This may well overestimate the problem – as not everyone will actually need or likely benefit from anti-obesity treatments (BMI measures size – not health!).

In fact, if we apply the actual WHO definition of obesity, namely the presence of abnormal or excess body fat that impairs health, we can perhaps readily reduce this number by about 5-10% (anyone with Edmonton Obesity Stage 0) obesity, as these individuals are pretty healthy despite their excess weight. As there is no evidence that these rather healthy individuals would experience any long-term benefits from anti-obesity treatments, it would be entirely reasonable to take a “watch and wait” approach.

The 7,000,000 also includes an additional 15-20% of people, who would have rather mild impairments in health (Edmonton Obesity Stage 1), associated with a very low long-term risk – for these there is also no proven long-term benefit of obesity treatment.

Thus, we can readily exclude about 20 to 30% of individuals for whom the risk-benefit ratio (and thus, the cost-benefit relationship) would hardly justify the use of prescription medications.

This would reduce the number needed to treat by as many as 2 million – leaving us with about 5,000,000 left to treat.

Of these (by definition), all would have Edmonton Obesity Stage 2 or higher, meaning that they will all have some obesity related health impairments.

However, many of these individuals will have obesity related health risks (e.g. hypertension, diabetes, sleep apnea) that are currently well managed with other available treatments (e.g. anti-hypertensive or anti-diabetic medications, CPAP, etc.). For these well-managed patients, it is not clear what additional value anti-obesity medications would offer.

Let us assume that this number of well managed patients is about 50% of the remaining 5,000,000 – this leaves us with only 2,500,000 individuals with obesity related health problems that are not well managed with the available treatments for their comorbidities. It is probably only in these individuals that medical obesity treatment would make sense – both in terms of cost and benefit.

Let us further assume that for another 50% of the remaining for various reasons (e.g. too sick, too old, no ready access to medically supervised care, not interested in obesity treatment, etc.) medical treatment for obesity is not feasible.

This would leave us with only about 1,250,000 patients where medical treatment with prescription drugs would be both practical and likely cost-effective.

This is now a much more manageable problem. In fact, this is only about half the number of Canadians currently living with diabetes, a problem that is routinely managed with medical treatments.

So where are the anti-obesity treatments for these patients?

That will be the topic of tomorrow’s post.

@DrSharma
Edmonton, AB

 

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We Desperately Need Scalable Treatments For Obesity

NN Benefits White Paper CoverObesity, defined as the presence of abnormal or excess body fat that impairs health, currently affects 100s of millions of people worldwide.

Although “weight-loss” is a booming global multi-billion dollar business, we desperately lack effective long-term treatments for this chronic disease – the vast majority of people who fall prey to the natural supplement, diet, and fitness industry will on occasion manage to lose weight – but few will keep it off.

Thus, there is little evidence that the majority (or even just a significant proportion) of people trying to lose weight with help of the “commercial weight loss industry” will experience long-term health benefits.

When it comes to evidence-based treatments, there is ample evidence that behavioural interventions can help patients achieve and sustain important health benefits, but the magnitude of sustainable weight loss is modest (3-5% of initial weight at best).

Furthermore, although one may think that “behavioural” or “lifestyle” interventions are cost-effective, this is by no means the case. Successful behaviour change requires significant intervention by trained health professionals, a limited and expensive resource to which most patients will never have access. Moreover, there is ample evidence showing maintenance of long-term behaviour change requires significant on-going resources in terms of follow-up visits – thus adding to the cost.

This severely limits the scalability of behavioural treatments for obesity.

If for example, every Canadian with obesity (around 7,000,000) met with a registered dietitian just twice a year on an ongoing basis (which is probably far less than required to sustain ongoing behaviour change), the Canadian Health Care system would need to provide 14,000,000 dietitian consultations for obesity alone.

Given that there are currently fewer than 10,000 registered dietitians in Canada, each dietitian would need to do 14,000 consultations for obesity annually (~ 70 consultations per day) or look after approximately 7,000 clients living with obesity each year. Even if some of these consultations were not done by dietitians but by less-qualified health professionals, it is easy to see how this approach is simply not scalable to the size of the problem.

A similar calculation can be easily made for clinical psychologists or exercise physiologists.

Thus, behavioural interventions for obesity, delivered by trained and licensed  healthcare professionals are simply not a scalable (or cost-effective) option.

At the other extreme, we now have considerable long-term data supporting the morbidity, mortality, and quality of life benefits of bariatric surgery. However, bariatric surgery is also not scalable to the magnitude of the problem

There are currently well over 1,500,000 Canadians living with obesity that is severe enough to warrant the costs and risks of surgery. However, at the current pace of 10,000 surgeries a year (a number that is unlikely to dramatically increase in the near future), it would take over 150 years to operate every Canadian with severe obesity alive today.

This is where we have to look at how Canada has made significant strides in managing the millions of Canadians living with other chronic diseases?

How are we managing the over 5,000,000 Canadians living with hypertension?

How are we managing the over 2.5 million Canadians living with diabetes?

How are we managing the over 1.5 million Canadians living with heart disease?

The answer to all is – with the help of prescription medications.

There are now millions of Canadians who benefit from their daily dose of blood pressure-, glucose-, and cholesterol-lowering medications. The lives saved by the use of these medications in Canada alone is in the 10s of thousands each year.

So, if millions of Canadians take medications for other chronic diseases (clearly a scalable approach), where are the medications for obesity?

Sadly, there are currently only two prescription medications available to Canadians (neither scalable, one due to cost the other due to unacceptable side effects).

So what would it take to find treatments for obesity that are scalable to the magnitude of the problem?

More on that in tomorrow’s post.

@DrSharma
Edmonton, Ab

 

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Does Gastric Bypass Surgery Change Body Weight Set Point?

sharma-obesity-surgery3The Holy Grail of obesity treatment is to find a way to revere the resetting of the body weight set point from the highest achieved body weight to something that is lower.

Unfortunately, all current treatments fail to “cure” obesity, as they fail to reset the set point to what would be considered “normal weight”. This makes ongoing treatment (be it behavioural, medical, or surgical) inevitable.

For all we know, any attempt at creating and sustaining weight loss regularly activates complex neurohormonal responses that serve to promote weight regain.

The only treatment, which may prove to be an exception is bariatric surgery (although this also only works as long as the surgery is in place – reverse the surgery, and the weight comes back).

Now, a paper by Hans Rudi Berthoud and colleagues, published in the International Journal of Obesity takes an in depth look at if and how gastric bypass surgery changes the body weight set point.

The paper reviews the data in support of the notion that surgery physiologically reprograms the body weight defense mechanism.

Thus, behavioural studies in animal models have shown that the defended body weight is indeed lowered after RYGB and sleeve gastrectomy.

For example, after surgeries, rodents return to their preferred lower body weight if over- or underfed for a period of time, and the ability to drastically increase food intake during the anabolic phase strongly argues against the physical restriction hypothesis.

Furthermore, these authors have also demonstrated that the defense of fat mass is less efficient (whereas defense of lean mass remains intact) after surgery.

However, as they point out,

“…the underlying mechanisms remain obscure. Although the mechanism involves central leptin and melanocortin signaling pathways, other peripheral signals such as gut hormones and their neural effector pathways likely contribute.”

Trying to elucidate the exact underlying mechanisms will hopefully not just improve our understanding of how bariatric surgery works, but also hopefully ultimately lead to the development of novel medical treatments that specifically target the body weight set point and its defence.

@DrSharma
Monterrey, Mexico

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