Follow me on

How Far Are We From Once-Weekly Medications For Obesity?

Anyone who follows these pages is aware of the fact that we desperately lack better medical treatments for obesity.

Last year, Health Canada approved the glucagon-like peptide 1 (GLP-1) analogue liraglutide (Saxenda(R)) for obesity treatment, which although effective and generally well-tolerated, has to be administered by daily injections.

Now, the results of the SUSTAIN-6 trial, published in the New England Journal of Medicine, show that the once weekly injection of the GLP-1 analogue semaglutide, not only decreases cardiovascular events, but also significantly lowers body weight, a promising finding for future obesity treatment with this drug.

The SUSTAIN 6 trial randomised 3297 patients with type 2 diabetes to once-weekly semaglutide (0.5 mg or 1.0 mg) or placebo for 104 weeks.

At baseline, 2735 of the patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both.

The primary outcome (MACE) occurred in 108 of 1648 patients (6.6%) in the semaglutide group and in 146 of 1649 patients (8.9%) in the placebo group (hazard ratio, 0.74).

Nonfatal myocardial infarction occurred in 2.9% of the patients receiving semaglutide and in 3.9% of those receiving placebo (hazard ratio, 0.74); nonfatal stroke occurred in 1.6% and 2.7%, (hazard ratio, 0.61).

While average body weight at week 104 remained stable in the placebo group, it decreased by 3.6 kg in the semaglutide 0.5 mg group and and 4.9 kg in the semaglutide 1.0 mg group.

While this may not seem spectacular, it is important to remember that weight loss is notoriously difficult in patients with type 2 diabetes and that this was a diabetes and not an obesity trial, in which case participants would have also been counselled to change their diet and activity levels to achieve weight loss.

Thus, one can only speculate on what the differences in body weight would have been had the participants been actually trying to lose weight.

That said, it was perhaps surprising to note that fewer serious adverse events occurred in the semaglutide group, although more patients discontinued treatment because of adverse events, mainly gastrointestinal.

It will be interesting to see how well semaglutide fares in studies in which this treatment is assessed for the obesity indication, which will hopefully bring us closer to a once-weekly medication for obesity.

In the meantime, once-daily liraglutide 3.0 mg is certainly a welcome addition to medical management of obesity, but clearly there is more to come in terms of harnessing GLP-1 for obesity management.

@DrSharma
Edmonton, AB

Disclaimer: I have received consulting and speaking honoraria from Novo Nordisk, the makers of liraglutide and semaglutide

Comments

5th Canadian Obesity Summit – Call For Abstracts And Workshops Now Open

banff-springs-hotelEvery two years the Canadian Obesity Network holds its National Obesity Summit – the only national obesity meeting in Canada covering all aspects of obesity – from basic and population science to prevention and health promotion to clinical management and health policy.

Anyone who has been to one of the past four Summits has experienced the cross-disciplinary networking and breaking down of silos (the Network takes networking very seriously).

Of all the scientific meetings I go to around the world, none has quite the informal and personal feel of the Canadian Obesity Summit – despite all differences in interests and backgrounds, everyone who attends is part of the same community – working on different pieces of the puzzle that only makes sense when it all fits together in the end.

The 5th Canadian Obesity Summit will be held at the Banff Springs Hotel in Banff National Park, a UNESCO World Heritage Site, located in the heart of the Canadian Rockies (which in itself should make it worth attending the summit), April 25-29, 2017.

Yesterday, the call went out for abstracts and workshops – the latter an opportunity for a wide range of special interest groups to meet and discuss their findings (the last Summit featured over 20 separate workshops – perhaps a tad too many, which is why the program committee will be far more selective this time around).

So here is what the program committee is looking for:

  • Basic science – cellular, molecular, physiological or neuronal related aspects of obesity
  • Epidemiology – epidemiological techniques/methods to address obesity related questions in populations studies
  • Prevention of obesity and health promotion interventions – research targeting different populations, settings, and intervention levels (e.g. community-based, school, workplace, health systems, and policy)
  • Weight bias and weight-based discrimination – including prevalence studies as well as interventions to reduce weight bias and weight-based discrimination; both qualitative and quantitative studies
  • Pregnancy and maternal health – studies across clinical, health services and population health themes
  • Childhood and adolescent obesity – research conducted with children and or adolescents and reports on the correlates, causes and consequences of pediatric obesity as well as interventions for treatment and prevention.
  • Obesity in adults and older adults – prevalence studies and interventions to address obesity in these populations
  • Health services and policy research – reaserch addressing issues related to obesity management services which idenitfy the most effective ways to organize, manage, finance, and deliver high quality are, reduce medical errors or improve patient safety
  • Bariatric surgery – issues that are relevant to metabolic or weight loss surgery
  • Clinical management – clinical management of overweight and obesity across the life span (infants through to older adults) including interventions for prevention and treatment of obesity and weight-related comorbidities
  • Rehabilitation –  investigations that explore opportunities for engagement in meaningful and health-building occupations for people with obesity
  • Diversity – studies that are relevant to diverse or underrepresented populations
  • eHealth/mHealth – research that incorporates social media, internet and/or mobile devices in prevention and treatment
  • Cancer – research relevant to obesity and cancer

…..and of course anything else related to obesity.

Deadline for submission is October 24, 2016

To submit an abstract or workshop – click here

For more information on the 5th Canadian Obesity Summit – click here

For sponsorship opportunities – click here

Looking forward to seeing you in Banff next year!

@DrSharma
Edmonton, AB

Comments

Arguments For Calling Obesity A Disease #3: Once Established It Becomes A Lifelong Problem

Screen Shot 2016-05-22 at 8.54.34 PMContinuing in my miniseries on arguments that support calling obesity a disease, is the simple fact that, once established, it behaves like a chronic disease.

Thus, once people have accumulated excess or abnormal adipose tissue that affects their health, there is no known way of reversing the process to the point that this condition would be considered “cured”.

By “cured”, I mean that there is a treatment for obesity, which can be stopped without the problem reappearing. For e.g. we can cure an ear infection – a short course of antibiotics and the infection will resolve to perhaps never reappear. We can also cure many forms of cancer, where surgery or a bout of chemotherapy removes the tumour forever. Those conditions we can “cure” – obesity we cannot!

For all practical purposes, obesity behaves exactly like every other chronic disease – yes, we can modify the course or even ameliorate the condition with the help of behavioural, medical or surgical treatments to the point that it may no longer pose a health threat, but it is at best in “remission” – when the treatment stops, the weight comes back – sometimes with a vengeance.

And yes, behavioural treatments are treatments, because the behaviours we are talking about that lead to ‘remission’ are far more intense than the behaviours that non-obese people have to adopt to not gain weight in the first place.

This is how I explained this to someone, who recently told me that about five years ago he had lost a substantial amount of weight (over 50 pounds) simply by watching what he eats and maintaining a regular exercise program. He argued that he had “conquered” his obesity and would now consider himself “cured”.

I explained to him, that I would at best consider him in “remission”, because his biology is still that of someone living with obesity.

And this is how I would prove my point.

Imagine he and I tried to put on 50 pounds in the next 6 weeks – I would face a real upward battle and may not be able to put on that weight at all – he, in contrast, would have absolutely no problem putting the weight back on.

In fact, if he were to simply live the way I do, eating the amount of food I do, those 50 lbs would be back before he knows it.

His body is just waiting to put the weight back on whereas my biology will actually make it difficult for me simply put that weight on.

This is because his “set-point”, even 5 years after losing the weight, is still 50 lbs higher than my “set-point”, which is around my current weight (the heaviest I have ever been).

Whereas, he is currently working hard against his set-point, by doing what he is doing (watching what he eats, following a strict exercise routine), I would be working against my set-point by having to force myself to eat substantially more than my body needs or wants.

That is the difference! By virtue of having had 50 lb heavier, his biology has been permanently altered in that it now defends a weight that is substantially higher than mine.

His post-weight loss biology is very different from mine, although we are currently at about the same weight.

This is what I mean by saying he is in “remission”, thanks to his ongoing behavioural therapy.

Today, we understand much of this biology. We understand what happens when people try to lose weight and how hard the body fights to resist weight loss and to put the weight back on.

This is why, for all practical purposes, obesity behaves just like every other chronic disease and requires ongoing treatment to control – no one is ever “cured” of their obesity.

Not even people who have bariatric surgery – reverse the surgery and before you know it, the weight is back.

So, if for all practical purposes, obesity behaves like a chronic disease, why not just call a spade a spade?

@DrSharma
Edmonton, AB

For an illustration on why obesity acts like a chronic disease watch this short TEDx talk

Comments

Arguments Against Obesity As A Disease #9: Its Just A Risk Factor

sharma-obesity-blood-pressure4Next, in my miniseries on arguments I commonly hear against the notion of calling obesity a disease, is that it is “just a risk factor” for other diseases.

This may be true, if you just (wrongly) considered elevated BMI as your definition of obesity, because no doubt, people with higher BMI levels carry a higher risk for obesity related complications including type 2 diabetes, sleep apnea, fatty liver disease, hypertension – just to name a few. (Note that increased risk is not the same as actually having the condition!).

However, when you use the actual WHO definition of obesity, namely, “accumulation of excess or abnormal fat that impairs health”, obesity is no longer just a risk factor – it is now (by definition) impairing your health, which makes it far more than just a risk factor.

So while someone with a BMI of 35 may be at risk of developing obesity (not the same as having it), when their excess fat actually starts impairing their health, it de facto becomes a disease in its own right.

Even then, one might argue that obesity itself is not the disease, rather the complications of obesity are the real disease.

This notion is both right and wrong.

There are many conditions that are both diseases in their own right as well as risk factors for other diseases or complications.

Take type 2 diabetes for instance – it is both a disease in itself but also a risk factor for coronary heart disease or end-stage kidney disease.

Take hypertension – a disease in its own right but also a risk factor for strokes and heart attacks.

Take gastro-oesophageal reflux disease, which is also a risk factor for Barrett’s disease and oesophageal cancer.

Take fatty liver disease, which is also a risk factor for cirrhosis.

Gall bladder stones, which is also a risk factor for pancreatitis.

Multiple sclerosis, which is also a risk factor for neurogenic bladder and pyelonephritis.

The list goes on and on.

So just because obesity is also a risk factor for a wide range of other medical problems, it does not make obesity any less of a disease in its own right.

When excess or abnormal body fat affects health – it’s a disease. When it doesn’t, it’s at best a risk factor.

That, is perhaps a subtle but important distinction.

@DrSharma
Toronto, ON

Comments

Arguments Against Obesity As A Disease #5: Reduces Personal Responsibility

diet journalIn my miniseries on arguments that I often hear against calling obesity a chronic disease, I now turn to the objection that declaring obesity a disease would reduce or even abolish personal responsibility.

The argument being, that the term “disease” carries the connotation of being inevitable and will thus reduce motivation in patients to do anything about it.

This is complete nonsense!

When has calling something a disease ever taken away an individuals “responsibility” to do what they can to avoid or ameliorate it?

Take for example type 2 diabetes – a very avoidable and modifiable condition. Calling diabetes a disease does not mean that the individual can do nothing to prevent it or that, once it occurs, the patient can do nothing to change the course of the disease – of course they can and should and often do!

Or take people with a high risk of heart disease or lung disease or bone and joint disease or even cancer – in no instance do we expect less of patients to do their part in helping manage these conditions just because we call them “diseases”.

There is even a term for this – it is called “self-management” – a key principle of chronic disease management.

The course of almost every chronic disease can be changed by whether or not patients change their diet, follow their exercise program, monitor their symptoms, take their medications, come in for their visits – all a matter of “responsibility” if you so wish.

So just how exactly would calling obesity a disease take away from any of this?

Frankly, I cannot help but sense that people who use this argument most often, are erring on the side of “shame and blame” and probably still see obesity largely as a matter of personal “choice” rather than the complex multifactorial problem that it actually is.

Indeed, the opponents often appear “morally” opposed to the very notion of accepting obesity as a disease, as it now gives people the “excuse” to not do anything about it. Sorry, but this whole line of arguing reeks of nothing less than weight bias and discrimination.

As far as I can tell, calling something a disease often leads to exactly the opposite response – when obesity happens (and it can happen to anyone), it places a tremendous mental, physical and social burden on the people who get it – no matter what you call it.

People living with obesity have no greater or lesser “responsibility” of contributing to the self-management of their disease, than people living with hypertension, diabetes, depression, heart disease, or cancer – people living with any disease should be doing what they can – why would obesity be any different?

@DrSharma
New Orleans, LA

Comments