In the meantime, Novo Nordisk, the maker of liraglutide, is continuing its development of a new GLP-1 analogue semaglutide as a once-weekly injection for the treatment of diabetes and obesity.
Last week the company released topline data from its SUSTAIN 3 study, a phase 3a trial in around 800 patients with type 2 diabetes randomized (open-label) to once-weekly semaglutide 1.0 mg vs. exenatide 2.0 mg (another once weekly GLP-1 analogue) over 56 weeks.
Participants on semaglutide achieved a greater reduction in A1c (1.5% vs. 0.9%; baseline = 8.4%) and weight loss (5.6 kg vs. 1.8 kg; baseline = 96 kg) compared to exenatide.
In general, adverse events (mainly GI-symptoms) were as expected for GLP-1 analogues with a rate of nausea twice as high with semaglutide compared to eventide (22% vs. 11%).
The overall discontinuation rate due to adverse events was slightly higher with semaglutide than eventide but fairly low overall (9.4% vs. 7.2%).
It should be noted that this was a diabetes and not an obesity study – so the almost 6% weight loss is indeed quite impressive (weight loss in studies designed to test drugs for obesity tends to be higher as patients are also advises to change their diet and physical activity).
According to Novo Nordisk, phase 2 dose-ranging trials of semaglutide in obesity could begin as early as next year – certainly an interesting development to watch.
Disclaimer: I have received honoraria as a consultant and speaker from Novo Nordisk
Yesterday, I attended the inaugural networking event of the Canadian Obesity Network’s Toronto Chapter. Judging by the enthusiasm of the almost 100 folks who came out to this event, this chapter appears off to a great start.
As expected for any CON event, the participants came from virtually every walk of interest in obesity – from professional to personal – research, prevention, clinic, policy, industry, NGOs.
Hopefully, we will see similar activities and chapters starting across Canada in the coming months – the success off this event shows that there is a dire need for local networking to address local issues related to obesity prevention and management.
For more information on the Toronto Chapter (CON-YYZ) click here.
For more information on how to start a CON chapter in your city click here.
Anyone who has closely followed my writings on this topic will know by now that health for a given individual cannot be measured by simply stepping on a scale (or for that matter using a measuring tape).
There are indeed individuals who appear rather healthy even at BMI levels considered to be well into the obesity range (just how many depends on your definition of “healthy”).
In an article and commentary that appears in the American Journal of Epidemiology, Juan Pablo Rey-López and colleagues from the School for Policy Studies, University of Bristol,UK, argue that the notion of “metabolically healthy obesity” (MHO), if anything is distracting and even counterproductive to public health efforts to prevent obesity.
They argue that,
“the MHO phenotype is not benign and as such has very limited relevance as a public health target.”
Throughout the article, the authors indeed make the oft-heard arguments for a population wide approach based on the notion that even a small left-shift in the weight distribution curve (as popularized by Geoffrey Rose) can have a potentially large influence on the population burden of excess weight.
This is not something anyone would argue with – at least at a population level and when the issue is prevention.
Unfortunately, Rey-López and colleagues then fall into the trap of pooh-poohing the research efforts around better trying to understand exactly why there is such a variation in how excess weight may (or may not) affect an individual’s health.
“More efforts must be allocated to reducing the distal and actual causal agents that lead to weight gain, instead of the current disproportionate scientific interest in the biological processes that explain the heterogeneity of obesity.”
Furthermore, they argue against further investments into obesity treatments:
“Nevertheless, it should be openly recognized that further investments in this predominantly individual approach will not reverse the obesity epidemic, because 1) medical therapies or dramatic lifestyle changes do not modify the distal causes of obesity (i.e., modern processed food and the built environment) and 2) individualized lifestyle modifications are commonly unsuccessful and inaccessible.“
The two facts that are largely ignored in this discussion are 1) that efforts at prevention (no matter how effective) are not helping the millions of people already living with this problem and 2) trying to find better treatments by learning more about the biology of this condition is exactly how we have found treatments for a host of other conditions ranging from diabetes to hypercholesterolemia and that these treatments have indeed allowed millions of people with these conditions to live productive and meaningful lives.
Personally, I find that the line of argument presented by the authors reeks of discrimination against people living with this problem. Thus, I cannot help but think that the authors consider people with obesity a “lost cause” not worthy of the investment into finding or providing better treatments.
Whether or not the discussions about MHO will help advance the field or not is certainly debatable.
Wether pitching prevention against treatment has the potential to actually harm people living with this problem is not.
Thus, a study by Asheley Skinner and colleagues, published in the New England Journal of Medicine, shows that increased cardiometabolic risk is tightly linked with severe obesity both in children and young adults.
The study looks at cross-sectional data from overweight or obese children and young adults (3-19 yrs) who were included in the US National Health and Nutrition Examination Survey (NHANES) from 1999 through 2012.
Among 8579 children and young adults with a body-mass index at the 85th percentile or higher (according to the Centers for Disease Control and Prevention growth charts), 46.9% were overweight, 36.4% had class I obesity, 11.9% had class II obesity, and 4.8% had class III obesity.
Overall, for a given weight, males tended to have higher cardiometabolic risk than females.
Even after controlling for age, race or ethnic group, more severe obesity maps more likely to be associated with low HDL cholesterol level, high systolic and diastolic blood pressures, and high triglyceride and glycated hemoglobin levels.
Importantly, while this relationship was constantly present in males, the there were fewer significant differences in these variables according to weight category among female participants, suggesting that for a given body weight, girls were less likely to be at cardiometabolic risk compared to boys.
Thus, while body weight (or body fat) may not be a precise measure of individual health, the risk for having one or more cardiometabolic risk factor increases substantially with increasing severity of obesity.
However, it is also important to note that even in kids and youth with class III obesity, 70% of participants had normal lipids and about 90% of participants did not have elevated blood pressure or glycated hemoglobin.
This points to the fact that for a given body weight there is indeed wide variability in whether or not someone actually has cardiometabolic risk factors.
Thus, whether or not it makes sense to target every kid that presents with an elevated BMI for intervention, remains to be shown – most likely such an approach would probably not be cost-effective.
As in adults, it seems that interventions in kids are probably best targeted by global risk rather than simply by numbers on a scale.
Next week, the newly formed Toronto Chapter of the Canadian Obesity Network (CON-YYZ) will be hosting its inaugural networking event at the MaRS Discovery District in Toronto.
The event titled Roadblocks & Detours will explore the barriers and challenges to improving obesity prevention and management in Toronto and beyond.
The panel and speakers will include Dr. Sean Wharton (Internist and Chapter President), Sandra Elia (Life Coach and host of Your Daily Diet – A Spiritual Guide to Healthy Body Size), Dr. Cynthia Maxwell (Associate Professor, Maternal-Fetal Medicine, Mount Sinai Hospital) and yours truly as the key-note speaker.
The event will be moderated by Deborah Schwartz (Senior Analyst on the Health System Research team at the Canadian Institute for Health Information and PhD candidate in psychology at the University of Toronto).
I look forward to a most interesting discussion and the opportunity to meet and network with all of CON’s members in Toronto.
The event takes place
Tuesday October 6, 2015 from 6:00pm – 9:00pm
MaRS Discovery District
101 College Street, Room CR-2
Toronto, ON M5G 1L7 Canada
To learn more about the CON Chapter in Toronto, click here
To register for CON-YYZ’s inaugural event, click here.