Readers will recall, that once-weekly injections of the novel long-acting GLP-1 analogue semaglutide was recently shown (in patients with type 2 diabetes) to result in a rather impressive weight loss.
Now, a phase II dose-finding study comparing various oral doses of semaglutide to subcutaneous injections in patients with type 2 diabetes was just published in JAMA.
The 26-week trial with 5-week follow-up included around 600 patients with type 2 diabetes and insufficient glycemic control using diet and exercise alone or a stable dose of metformin were randomized to once-daily oral semaglutide of 2.5 mg (n = 70), 5 mg (n = 70), 10 mg (n = 70), 20 mg (n = 70), 40-mg 4-week dose escalation (standard escalation; n = 71), 40-mg 8-week dose escalation (slow escalation; n = 70), 40-mg 2-week dose escalation (fast escalation, n = 70), oral placebo (n = 71; double-blind) or once-weekly subcutaneous semaglutide of 1.0 mg (n = 70) for 26 weeks.
Mean change in HbA1c level from baseline to week 26 decreased with oral semaglutide (dosage-dependent range, −0.7% to −1.9%) and subcutaneous semaglutide (−1.9%) and placebo (−0.3%);
Significant reductions were also seen in body weight with both oral (dosage-dependent range, −2.1 kg to −6.9 kg) and subcutaneous semaglutide (−6.4 kg) vs placebo (−1.2 kg)>
Adverse events (largely consisting of mild to moderate gastrointestinal events) were as expected and relatively comparable between the treatment arms.
Although this was a diabetes study, these findings clearly hold promise for the further development of an oral formulation of semaglutide for the obesity indication.
Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide.
This week, I am in Tønsberg, Norway, speaking at the annual meeting of the European Association for the Study of Obesity (EASO) Collaborating Centres on Obesity Management (COMs).
This is a pan-Euoropean network of over 75, that includes academic, public and private clinics where children and adults with obesity are managed by holistic teams of specialists delivering comprehensive state-of- the-art clinical care.
The EASO-COMs also work closely to ensure quality control, data collection, and analysis as well as for education and research for the advancement of obesity care and obesity science.
Current plans foresee establishing 100 new COMs by 2020. There are also plans to develop an international exchange and mentoring program to increase competencies and treatment knowledge across Europe.
Other important EASO initiatives in this regard include a knowledge transfer series involving e-Learning modules for obesity management based on the Canadian Obesity Network’s initiative with mdBriefCase.
I certainly look forward to networking with and learning from my European colleagues over the next couple of days.
Further details on the criteria for becoming a EASO COM are available here.
The following is a guest post from my Australian colleague Dr. Georgia Rigas, who reports on the recent recognition of obesity as a disease by the Royal Australian College of General Practice (RACGP).
Last week, the Royal Australian College of General Practice (RACGP) President, Dr Seidel recognised obesity as a disease. The RACGP is the first medical college in Australia to do so.
This was exciting news given that we have just observed World Obesity Day a few days ago.
According to the Australian Bureau of Statistics1, over 60% of Australian adults are classified as having overweight or obesity, and more than 25% of these have obesity [defined as a Body Mass Index (BMI) ≥30] (ABS2012). Similarly in 2007, around 25% of children aged 2–16 were identified as having overweight or obesity, with 6% classified as having obesity (DoHA 2008). These are alarming statistics.
The recent published BEACH data for 2015-162, showed that the proportion of Australian adults aged 45-64yo presenting to GPs has almost doubled in the last 15+ years. Worryingly the numbers are predicted to continue rising, with 70% of Australians predicted to have overweight or obesity by 2025. Embarrassingly, the BEACH data also indicated that <1% of GP consultations centred around obesity management.
So obviously what we, as GPs have been doing..,or rather not doing…isn’t working!
The RACGP’s General Practice: Health of the Nation 2017 3report found Australian GPs identified obesity and complications from obesity as one of the most significant health problems Australia faces today and will continue to face in coming years as the incidence of obesity continues to rise.
But what are we doing about it?…. I think the answer is evident… clearly not enough!
Thus, we can only hope that this announcement by the RACGP will have a ripple effect, with other medical colleges in Australia and then the Australian Medical Association following suit.
So what does this mean in practical terms?
For those individuals with obesity (BMI ≥30) with no “apparent” comorbidities or complications from their excess weight…[though you could argue they will develop (if not already) premature osteoarthritis of the weight bearing joints…..] would be eligible for a chronic care plan [government subsidized access to a limited number of consultations with allied health services] given the chronic and progressive nature of the disease.
It also highlights the need for GPs to start screening ALL patients in their practice-young and old;
- for children their parameters need to be plotted on a BMI-for-age chart;
- for adults BMI & waist circumference, taking into account their ethnicity (as different cut- offs for different ethnic groups) and physical activity levels (if they are muscular or not) are important
This powerful statement should help clear any ambivalence.
Why is there a therapeutic inertia when it comes to treating people with obesity?
People with obesity suffer significant degrees of stigma, discrimination and weight bias and as a result may be reluctant to access healthcare. Today, we are giving these patients a voice.
As health care professionals, let’s not forget that the health message needs to change from “lose weight” to “gain health” in recognition that obesity is about more than body weight.
In closing, to effectively and equitably work towards reducing obesity in our communities, we need a balanced combination of both individual and public health measures. This media release by the RACGP shows their commitment to both the primary prevention and the treatment of this life- threatening disease, to ensure better health outcomes and quality of life for all Australians.
Dr Georgia Rigas, MBBS FRACGP
SCOPE certified obesity doctor
Bariatric Medical Practitioner
Yesterday (World Obesity Day), the European Regional Office of the World Health Organisation released a brief on the importance of weight bias and obesity stigma on the health of individuals living with this condition.
The brief particularly emphasises the detrimental effects of obesity stigma on children:
“Research shows that 47% of girls and 34% of boys with overweight report being victimized by family members. When children and young people are bullied or victimized because of their weight by peers, family and friends, it can trigger feelings of shame and lead to depression, low self-esteem, poor body image and even suicide. Shame and depression can lead children to avoid exercising or eatng in public for fear of public humiliation. Children and young people with obesity can experience teasing, verbal threats and physical assaults (for instance, being spat on, having property stolen or damaged, or being humiliated in public). They can also experience social isolation by being excluded from school and social activities or being ignored by classmates.
Weight-biased attitudes on the part of teachers can lead them to form lower expectations of students, which can lead to lower educa onal outcomes for children and young people with obesity. This, in turn, can affect children’s life chances and opportunities, and ultimately lead to social and health inequities. It is important to be aware of our own weight-biased attitudes and cautious when talking to children and young people about their weight. Parents can also advocate for their children with teachers and principals by expressing concerns and promo ng awareness of weight bias in schools. Policies are needed to prevent weight-victimization in schools.”
The WHO Brief has important messages for anyone working in public health promotion and policy:
Take a life-course approach and empower people:
Monitor and respond to the impact of weight-based bullying among children and young people (e.g. through an -bullying programmes and training for educa on professionals).
• Assess some of the unintended consequences of current health-promo on strategies on the lives and experiences of people with obesity. For example:
- Do programmes and services simplify obesity?
- Do programmes and services use stigmatizing language?
- Is there an opportunity to promote body positivity/confidence in children and young people in health promotion while also promoting healthier diets and physical activity?• Give a voice to children and young people with obesity and work with families to create family-centred school health approaches that strengthen children’s resilience and consider positive outcomes including but not limited to weight.• Create new standards for the portrayal of individuals with obesity in the media and shift from use of imagery and language that depict people living with obesity in a negative light. Consider the following:
- avoiding photographs that place unnecessary emphasis on excess weight or that isolate an individual’s body parts (e.g. images that dispropor onately show abdomen or lower body; images that show bare midri to emphasize excess weight);
- avoiding pictures that show individuals from the neck down (or with face blocked) for anonymity (e.g. images that show individuals with their head cut out of the image);
- avoiding photographs that perpetuate a stereotype (e.g. ea ng junk food, engaging in sedentary behaviour) and do not share context with the accompanying wri en content.
Strengthen people-centred health systems and public health:
• Adopt people-first language in health systems and public health care services, such as a “patient or person with obesity” rather than “obese patient”.
• Engage people with obesity in the development of public health and primary health care programmes and services.
• Address weight bias in primary health care services and develop health care models that support the needs of people with obesity.
• Apply integrated chronic care frameworks to improve pa ent experience and outcomes in preventing and managing obesity. In addition:
- recognize that many patients with obesity have tried to lose weight repeatedly;
- consider that patients may have had negative experiences with health professionals, and approach patients with sensitivity and empathy;
- emphasize the importance of realistic and sustainable behaviour change – focus on meaningful health gains and
- explore all possible causes of a presenting problem, and avoid assuming it is a result of an individual’s weight status.
- Acknowledge the dificulty of achieving sustainable and significant weight loss.
Create supportive communities and healthy environments:
- Consider the unintended consequences of simplistic obesity narratives and address all the factors (social, environmental) that drive obesity.
- Promote mental health resilience and body positivity among children, young people and adults with obesity.
- sensitize health professionals, educators and policy makers to the impact of weight bias and obesity stigma on health and well-being.
Hopefully, these recommendations will find their way into the work of everyone working in health promotion and clinical practice.
The whole brief is available here.
A recent CMAJ article, by Ian Mosby and Tracey Galloway from the University of Toronto argues that one of the key reasons why we see obesity and diabetes so rampant in Canada’s indigenous populations, is the fact that widespread and persistent exposure to hunger during the notorious residential school system may have metabolically “programmed” who generations toward a greater propensity for obesity and type 2 diabetes.
There is indeed a very plausible biological hypothesis for this,
“Hunger itself has profound consequences for childhood development. Children experiencing hunger have an activated hypothalamic–pituitary–adrenal stress response. This causes increased cortisol secretion which, over the long term, blunts insulin response, inhibits the function of insulin-like growth factor and produces long-term changes in lipid metabolism. Through this process, the child’s physiology is essentially “programmed” by hunger to continue the cycle of worsening effects, with their bodies displaying a rapid tendency for fat-mass accumulation when nutritional resources become available.”
While the impact of hunger may well have been one of the key drivers or metabolic changes, the authors failed to acknowledge another (even more?) important consequence of residential schools – the impact on mental health.
Oddly enough, in a blog post I wrote back in 2008, I discussed the notion that the significant (and widespread) physical, emotional, and sexual abuse experienced by the generations of indigenous kids exposed to the residential school system would readily explain much of the rampant psychological problems (addictions, depression, PTSD, etc.) present in the indigenous populations across Canada today.
The following is an excerpt from this previous post:
This disastrous and cruel [residential school] policy resulted in much pain and despair in the First Nations’, Inuit and Metis people that lasts to this day (known as the “generational effect”). Sexual, physical and mental abuse was widespread; students were broken in heart and spirit; culture and identities were destroyed.
Much (if not all) of what ails the Aboriginal peoples of Canada can be traced back to this policy – including possibly issues that affect Aboriginal health to this day.
It is no secret that obesity and its consequences (e.g. diabetes) are rampant amongst the Aboriginal peoples of Canada. While poverty, breakdown of traditional lifestyle and culture and even genetic factors (thrifty genotype) have all been implicated in this, I wonder how much the misery caused by the residential school program had to contribute.
Early traumatic life experiences including sexual, mental and physical abuse as well as neglect and grief have all been implicated in binge eating disorder (BED) – in its purest form – the uncontrollable urge to devour large quantities of highly palatable high-caloric foods in response to emotional hunger. This behaviour has been interpreted as an emotional coping strategy, “filling the inner void”, building a physical protective barrier, etc., the ultimate result being excessive weight gain with all its consequences (the typical binger does not compensate by purging or excessive exercise).
In “treatment-seeking” patients with obesity, the prevalence of BED is estimated at 20-40%. Although I was unable to find a study that has applied the DSM-IV criteria for BED to an Aboriginal population – my guess is: the rates are probably high!
Given its distinct psychopathology, BED is highly responsive to psychotherapeutic approaches. In contrast, educational initiatives based on simply providing information on healthy lifestyles are useless.
Obesity is never an issue of “choice”. I have yet to meet anyone who “chooses” to be obese. This is most certainly also true for Canada’s Aboriginal population.”
“Adult Obesity in Brazil” is a free, online continuing professional development (CPD) program that provides 1 hour of accredited learning on the following topics:
- The importance of managing obesity
- How to manage obesity to reduce disease burden
- Behaviourial and pharmaceutical management
The program was developed in collaboration my Brazilian colleagues Cintia Cercato, Bruno Halpern, and Nelson Nardo Jr.
You can access the “Adult Obesity in Brazil” program online at no charge to receive one hour of accredited learning.
Registration is free.
For more information click here
Readers may have already heard about a recent study by Tim Althoff and colleagues from Stanford University, published in Nature, that analyses physical activity data collected from smart phones consisting of 68 million days of physical activity for 717,527 people, in 111 countries (only 46 of which were included in the study).
As one may expect, not only do activity levels vary widely across countries but also substantially within countries (which in general terms, the authors refer to as “activity inequality”).
It turns out that activity inequality and not actual levels of activity predict obesity rates (based on BMI).
“By quantifying the relationship between activity and obesity at the individual level, we were able to determine why a country’s activity inequality is a better predictor of obesity than average activity level. We find that the prevalence of obesity increases more rapidly for females than males as activity decreases. And while lower activity is associated with a substantial increase in obesity prevalence for low-activity individuals, there is little change in obesity prevalence among high-activity individuals. So given two countries with identical average activity levels, the country with higher activity inequality will have a greater fraction of low-activity individuals, many of them female, leading to higher obesity than predicted from average activity levels alone. These findings are analogous to the phenomenon revealed in past studies of the effects of income inequality on health, whereby a relatively small change in income (in our case, activity) for an individual at the bottom of the distribution can lead to substantial improvements in health. On the basis of our model relating activity inequality to obesity prevalence, we also performed a simulation experiment which, assuming perfect information (Methods), suggests that interventions focused on reducing activity inequality could result in a reduction in obesity prevalence up to four times greater than in population-wide approaches.”
The authors go on to discuss various limitation of their study but fail to mention the biggest limitation of all, the simple fact that correlations, no matter how strong or how large the data set, simply cannot prove causality.
Thus, while the data does prove the point that you can do all sorts of interesting analyses when you have large data sets, it simply does not not prove that activity levels (or activity inequality for that matter) actually has much to do with obesity at all.
Indeed, one could think of a number of confounders that would otherwise differentiate countries with high activity inequality that happen to have high obesity rates from countries that have low activity inequality and low obesity rates (let’s not even mention reverse causality).
Thus, as nice as the figures presented in the paper may be, it is really hard to follow the author’s conclusion that,
“Our findings can help us to understand the prevalence, spread, and effects of inactivity and obesity within and across countries and subpopulations and to design communities, policies, and interventions that promote greater physical activity.”
This is not to say that designing communities, policies, and interventions would not be of substantial health benefits – given all of the known benefits of physical activity.
Unfortunately, whether or not, these policies would do anything to prevent or reverse obesity is another matter altogether and remains as unclear after this study as before.
Why do doctors weigh people? Because, very early in medical school, we are taught that body weight is an important indicator of health.
While one may certainly argue about the value of a single weight measurement at any point in time (especially in adults), there is simply no denying that weight trajectories (changes in body weight – up or down) can provide important (often vital) clinical information.
Let’s begin with the easiest (and least arguable) situations of all – unintentional weight loss.
Among all clinical parameters one could possibly measure, perhaps non should be as alarming as someone losing weight without actively trying. In almost every single instance of “unintentional” weight loss, the underlying problem needs to be found, and more often than not, the diagnosis is probably serious (cancer is just one possibility).
As with any serious condition, the earlier you detect it, the sooner you can do something about it, therefore, the more often you weight someone, the more likely you will detect early “non-intentional” weight loss.
The contrary situation (un-intentional weight gain) is as important. When someone is gaining weight for no good reason, one needs to look for the underlying cause, which can include everything from an endocrine problem to heart failure.
On the other hand, weight stability, is generally a sign that things are probably “under control”, as they should be when energy homeostasis works fine and people are in energy balance.
Perhaps my own obsession with weighing people comes from my work in nephrology, where we obsess about people’s “dry weight” and use weight as a general means to monitor fluid status. The same is true for working with patients who have heart failure.
Note for all of the above, that while a single (random) weight measurement tells you very little (almost nothing) about anybody’s health status, unexplained changes in body weight are one of the most useful and important clinical signs in all of medicine. Obviously, to plot a trajectory, one has to start somewhere, which means that every patient needs to have a “baseline” body weight recorded somewhere in their chart. While this value may not provide any valuable information, the next one may.
This is why every single patient needs to be weighed at least once in a clinical setting.
As you will imagine, both the context and interpretation of serial weight measurements becomes most challenging in the setting of obesity management.
For one, there is no greater challenge than to suspect underlying “un-intentional” weight loss in someone who is actively trying to lose weight. When “suddenly” a weight loss strategy that was providing modest results “starts working” – all alarm bells should go off. Also, if weight loss is much better than “predicted” it is time to take a serious second look at what’s happening. Furthermore, you need to watch out for patients who are doing far better than expected (even after bariatric surgery) – it takes a keen clinical mind to watch out for weight loss that appears “too good to be true” (even if the patient is delighted to see the pounds drop off).
Also, in the obesity management setting, weight stability is an important clinical indicator. In someone at their maximum weight, it tells me that the patient is not actively gaining weight, which by definition means that the patient is in caloric balance – remember, the first sign of “success” in obesity management is when the patient stops gaining weight.
In someone, who has already lost weight (in the context of obesity management), weight stability means that the patient’s efforts are continuing (here weight stability is a means to monitor “control”) – weight regain means that the patient may have to re-engage in weight control efforts or (more often) that something has come up in that person’s life that is “sabotaging” their efforts and may need to be identified and addressed (e.g. lost a job, change in medication, depression, etc.). Again, the earlier you identify a “relapse”, the earlier you can intervene.
Finally, in someone attending an obesity clinic, who continues gaining weight, you can be sure that the underlying cause of weight gain has not yet been fully identified or addressed. In other words, the disease is not “controlled” and continues to “progress”.
Thus, patients must be aware, that asking not to be weighed (usually out of shame or embarrassment) derives their clinician of important and possibly “vital” information about their health status.
Again, while a single weight (or BMI) says very little about a patient’s health, changes in body weight (up or down) is a vital sign that should prompt further clinical investigation and possibly intervention.
None of this has anything to do with the fact that people can very well be healthy over a wide range of body shapes and sizes.
It also does not mean that we should take a “weight-centric” approach to obesity management – all of the usual HAES arguments remain valid, even when you regularly ask your patient to step on the scale.
Recording a weight trajectory should be no more “judgemental” than recording a fever chart in a patient with an infection – everything lies in the context and interpretation of the data.