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Diabetes Medication Canagliflozin Reduces Cardiovascular Events

>> Tuesday, June 13, 2017

The eagerly awaited results of the CANVAS trial were just released yesterday at the American Diabetes Association Meeting, and published simultaneously in the New England Journal of Medicine.

The CANVAS program was a cardiovascular outcome trial of the SGLT2 inhibitor, canagliflozin (Invokana).  This program enrolled 10,142 people with type 2 diabetes and high cardiovascular risk, and randomized them to receive either canagliflozin 100mg, canagliflozin 300mg, or placebo, in addition to their usual care.

After a mean of 3.6 years, they found that canagliflozin reduced the risk of a combination of cardiovascular death, non fatal heart attack and non fatal stroke by 14%, with the benefit being particular to those with established cardiovascular disease at baseline.  The individual outcomes above were not significantly reduced when considered separately, but were significant when considered together.   Canagliflozin also reduced the risk of hospitalization for congestive heart failure by 33%, reduced the risk of poor kidney outcomes by 40% (a composite of a sustained 40% reduction in GFR, need for renal replacement therapy, or death from renal causes), and reduced progression of albumin in the urine by 27%.

In terms of risks of canagliflozin, unexpectedly, there was an increase in the risk of amputation, with 3.3% of people on canagliflozin requiring an amputation (most commonly a toe or forefoot) during the course of the trial, vs 1.5% in the placebo group.    There was also an increase in the risk of fracture, with 15.4 fractures per 1000 patient years on canagliflozin, vs 11.9 per 1000 patient years in the placebo group.  There was an increased risk of genital yeast infection, as expected for this class of medications, but no increased risk of urinary tract infection.

The CANVAS program adds to our understanding of the SGLT2 class of medications.   As the EMPA REG trial showed us that the SGLT2 inhibitor empagliflozin (Jardiance) also reduces CV events in people with type 2 diabetes and cardiovascular disease, this is looking more likely to be a 'class effect' of the SGLT2 inhibitors (we still await the DECLARE study of the SGLT2 inhibitor dapagliflozin (Forxiga) to be completed).

In terms of the risks seen in the CANVAS trial, much discussion is underway in the medical and scientific community, and more studies will need to be done to better understand these findings.  As always, the benefit vs risk of any medication must be carefully considered in finding the best medications for each individual patient.

Disclaimer: I receive honoraria as as continuing medical education speaker and consultant from the makers of canagliflozin (Janssen), empagliflozin (Boehringer-Ingelheim and Lilly), and dapagliflozin (Astra Zeneca).  I am involved in research of SGLT2 inhibitors as a treatment of diabetes. 

Follow me on twitter! @drsuepedersen © 2017


New Class of Cholesterol Medication Prevents Heart Attacks

>> Saturday, February 4, 2017

Statin medications have long been the main class of medications that have been recommended to lower cholesterol, as they have been shown to be very powerful to reduce the risk of cardiovascular events.  Now, a new class of medications joins the ranks of statins: the PCSK9 inhibitor evolocumab (Repatha) has been shown to reduce cardiovascular events.

The top-line results of the study, called the FOURIER study, have now been released.  This was a study of 27,500 patients with cardiovascular disease who were already on optimized statin therapy, randomized to receive either evolocumab or placebo.  They found that evolocumab reduced the risk of their primary endpoint, which was the sum of cardiovascular death, non fatal heart attack, non fatal stroke, hospitalization for unstable angina, or coronary revascularization (angioplasty).

I am looking forward to learning more about the results of this trial and the amount by which risk was reduced - these data will be released in March at the American College of Cardiology meeting in Washington DC.  It will be interesting to compare these results to the results of the IMPROVE-IT trial, which showed that the combination of statin therapy with the cholesterol lowering medication ezetimibe lowered the risk of cardiovascular death, major coronary events, or non fatal stroke by 2.0 percentage points compared to statin therapy alone.

It is encouraging to see a new class of cholesterol medications being developed that reduce cardiovascular events.  There are many patients who do not tolerate statin therapy; perhaps the PCSK9 inhibitors may also reduce cardiovascular risk for them (studies on this are currently underway).  PCSK9 inhibitors are extremely expensive, which limits their use in clinical practice.  Perhaps with these data, guidelines will be revised and we may hopefully see more coverage options so that the benefits of PCSK9 inhibitors to reduce cardiovascular events can be more widely enjoyed.

Disclaimer: I have been involved in a clinical trial of PCSK9 inhibition. I have received honoraria as a medical education speaker and consultant from the makers of ezetimibe (Merck).

Follow me on twitter! @drsuepedersen © 2017


An 86 Year Old Ironman Inspiration!

>> Thursday, August 25, 2016

In line with last week's post about the amazing Olympic athletes, here's a woman who inspires me to the ends of the earth - meet Madonna Buder, who holds the world record for the oldest person to ever complete an Iron Man triathlon, at the age of... 82!

Buder caught the triathlon bug a little later in life, completing her first triathlon at age 52 and her first Ironman at age 56.  She has completed over 325 triathlons, including 45 Ironman distances (an Ironman is a 3860m swim, 180km bike, followed up by a 42km marathon run).

Now 86 years old, Buder is an inspiration to athletes everywhere, and was even featured in a Nike ad that was aired during the Olympics.

Way to go!!  Thanks so much to my friend Chantelle for telling me about this amazing woman.

Follow me on twitter! @drsuepedersen © 2016


Olympic Games - Best Weight At All Sizes

>> Wednesday, August 17, 2016

It has been a real inspiration and thrill to watch the elite athletes of the world compete at the Rio 2016 Summer Olympic Games.  Over the last couple of weeks, we have enjoyed watching a wide range of sports, from swimming, to basketball, to gymnastics, to track & field, and so much more.

Take a moment and consider the variation in body shapes and sizes amongst this year's incredible athletes:

Each of these sports have a fierce demand for the highest level of physical ability, the nature of which is unique to each individual sport.  Some require intense upper body strength, while others are more lower body oriented; some high anaerobic capacity; others are all about endurance.

I see a similar diversity in body shape and size in the athletes in my clinical practice as an endocrinologist: marathoners, crossfitters, cyclists, swimmers, football players, and so many others.  The sad reality is that those who are of larger body size will often tell me that they feel judged and assumed to be inactive or 'lazy' based on their shape and size by people who have absolutely no idea what that person is all about.

There is no more poignant reminder than watching these incredible Olympic athletes to never judge a book by its cover.

Follow me on twitter! @drsuepedersen © 2016


Gender Wars In Obesity

>> Thursday, May 19, 2016

Obesity is a medical condition that now affects about 25% of the Canadian adult population, with the prevalence being slightly higher amongst men than women.  Interestingly, it is most often women that seek help to treat their obesity.  In fact, in clinical research trials of obesity, enrolment is usually constituted by about 80% women and 20% men - we would much prefer a 50/50 split so that we could study both genders equally well, but the reality is that women are more interested to participate in programs or studies that may help them to lose weight.   Why is this?

Though the reasons are likely multiple and complex, and also different from person to person, it seems that at least some of this difference may be thanks to societal views on obesity in women vs men.   I heard a poignant commentary from a colleague at a meeting recently.  He said:

Next time you are in the grocery store or gas station, have a look at the magazine rack.  When you go to the section that is most often read by women - fashion magazines, women's fitness, social news etc - what do you see?  Thin women, often models that are underweight, in skin tight clothing, strutting their stuff and painting the image of what a woman 'should' look like.  

Now, head to the outdoor and sporting section, which is the section that men most often enjoy.  These men are often larger, dressed in bulky clothing, looking large and strong... while many of these photos are very muscular, many are often carrying excess fat tissue as well. 

This societal dichotomy is doubly unfortunate, because it leaves women with an inappropriate impression of what they 'should' look like, while it could leave men thinking that it may be desirable to carry excess body weight.

I would love to hear from my readers if this resonates with you - feel free to post a message at the end of this blog post.

Follow me on twitter! @drsuepedersen © 2016


JDRF Reaches Out To Fort McMurray Evacuees with Type 1 Diabetes

>> Friday, May 13, 2016

In the wake of the wildfires that have ravaged Fort McMurray, there have been many heartwarming stories of outreach and support to victims of this monumental natural disaster.

The JDRF (formerly known as the Juvenile Diabetes Research Foundation) is reaching out to Fort Mac victims living with type 1 diabetes to help ensure they have ongoing access to insulin, test strips and supplies.  Here is the media release directly from the JDRF:

Media Advisory
JDRF Canada Assisting Fort McMurray Individuals Living with Type 1 Diabetes

The North Central Alberta & Northwest Territories Chapter of JDRF Canada is coordinating with local type 1 diabetes (T1D) support groups to provide assistance for T1D families evacuated from Fort McMurray with their insulin related needs.

Families who were forced to evacuate may have limited access to insulin, test strips and other related supplies. Local social media groups for people living with T1D have been very active with families offering to share their supplies with families in need. “Many people are now in the Edmonton Area while others are in camps around Fort McMurray”, said Dorothy Ross, Regional Director for JDRF in Western Canada “We are compiling the lists of people that are in need with people who can share some of their supply, both in the Fort McMurray area and in other communities in the region.”

People who are either in need of or able to offer supplies can contact JDRF at1-855-428-0343 or local at 780-428-0343. For after hours support, please e-mail JDRF staff will coordinate resources with those in need.

About JDRF
JDRF is the leading global organization funding type 1 diabetes (T1D) research. JDRF’s goal is to progressively remove the impact of T1D from people’s lives until we achieve a world without T1D. JDRF collaborates with a wide spectrum of partners and is the only organization with the scientific resources, regulatory influence, and a working plan to better treat, prevent, and eventually cure T1D. As the largest charitable supporter of T1D research, JDRF is currently sponsoring $530 million in scientific research in 17 countries. For more information, please visit

Follow me on twitter! @drsuepedersen © 2016


What The Biggest Loser Teaches Us About Metabolism After Weight Loss

>> Sunday, May 8, 2016

Well, I never thought I would say this, but the show The Biggest Loser has been useful for something: it has taught us some important scientific lessons about just how much, and for how long, metabolism drops after weight loss.

(I say that the show is useless otherwise for a host of reasons: It portrays unsafe, dramatic means of weight loss that are not sustainable and gives many incorrect and inappropriate messages about obesity.  I could go on...)

Fourteen participants of The Biggest Loser agreed to have their metabolism measured before the weight loss program, at the end of the 30 week competition, and again 6 years later.

The study (which has been big in the news media in the last several days) was conducted at the National Institute of Health and published in the medical journal Obesity.  The baseline weight amongst these six men and eight women was 148.9kg, and they lost an average of 58kg at the end of the 30 week competition.   After 6 years, most participants regained a significant proportion of the weight lost during the show, with only one person not regaining any weight, and five people having returned to their baseline weight or above.

When they measured metabolism in these people before the competition and compared it to their metabolism 6 years later, they found that on average, their metabolism burned 499 fewer calories per day, compared to what would be expected for a person of that gender, age and body composition who had not previously lost weight.

Similar to an older study I previously blogged about, this teaches us that metabolism decreases markedly after weight loss, not only due to carrying around less weight, but also due to an additional, evolutionarily designed adaptation to defend our body weight. For The Biggest Loser contestants, this means that on average, they have to eat 500 calories less, every day, than they would if they weighed the same but had not come down from a higher weight in the past.  This metabolic adaptation goes on for at least six years after weight loss (based on this study) - and of course may well go on much longer, possibly indefinitely.

So how does a person handle this new lower metabolism after weight loss, to keep the weight off?  We can look to the American National Weight Control Registry to learn about habits that are associated with keeping weight off - the themes are lots of activity (at least an hour a day) and lots of self monitoring - read more on this here.

If you'd like to read more about The Biggest Loser study and the individual participants, the New York Times wrote an excellent article about it, including interviews with several participants - check it out here.

Follow me on twitter! @drsuepedersen © 2016


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