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Oral Semaglutide Is As Effective For Weight Loss As Injections

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. @DrSharma Tønsberg, Noway Disclaimer: I have served as a consultant for Novo Nordisk, the maker of semaglutide. 

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European Collaborating Centres for Obesity Management (EASO-COMs)

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. @DrSharma Tønsberg, Norway

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Residential Schools And Indigenous Obesity – More Than Just Hunger?

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… Read More »

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New Course: Adult Obesity Management in Brazil

For my many colleagues in Brazil, there is now a free accredited online continuing professional development (CPD) program developed in a collaboration between ABESO and the Canadian Obesity Network. “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 @DrSharma Edmonton, AB

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Weight Change (Not Weight!) Is A Vital Sign

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… Read More »

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