Type 2 Diabetes Medication Semaglutide Reduces Cardiac Risk

Great news from the diabetes world: semaglutide, a medication in development for the treatment of type 2 diabetes and obesity, has been shown to reduce the risk of cardiovascular events.

The SUSTAIN-6 study (a study in which I was an investigator) was a global study of about 3,300 people with type 2 diabetes, who were randomized to receive semaglutide subcutaneously (injected under the skin) once weekly vs placebo for treatment of their diabetes. They found that after 2 years of treatment, semaglutide reduced cardiovascular events (defined as a sum of non fatal heart attack, non fatal stroke, and cardiovascular death).  Exactly how much the risk is reduced is not yet public knowledge - the information is currently available in a press release only, with the exact data to be released at a later date.

Semaglutide is a GLP-1 receptor agonist, which helps the pancreas control the release of hormones involved in blood sugar control (insulin and glucagon), and also stimulates the fullness centre in the brain to tell a person that they feel full.  Thus, not only does it help with blood sugar control, it is also effective for weight loss.  Semaglutide is currently in development as both a type 2 diabetes treatment and as a treatment for obesity in people with or without diabetes (it is not yet available as a prescription).   Interestingly, while all GLP-1 receptor agonists currently available are administered by injection under the skin (similar to how insulin is administered), semaglutide is also currently under development as an oral medication. (ie as a pill)

This marks the third time in the last eight months that we have been so thrilled to hear that a medication designed for the treat type 2 diabetes decreases the risk of cardiovascular events: empagliflozin (trade name Jardiance) (read here) and liraglutide (trade name Victoza) (read here) reduce cardiovascular events as well.  These are landmark times for the world of type 2 diabetes, as prior to these studies, we had not definitively proven that a medication for treatment of type 2 diabetes could decrease the risk of cardiovascular events.  In fact, we have had great difficulty proving that improving blood sugar control by any means reduces cardiovascular events (though it is clear that improving blood sugar control reduces the eye and kidney complications of diabetes).

Amongst the class of GLP-1 receptor agonists, both liraglutide and semaglutide have shown that they reduce cardiovascular events (though the numbers on this are not yet available on either one), whereas lixisenatide (not available in Canada) did not decrease cardiovascular events.  It remains to be seen what effect the other GLP-1 receptor agonists available in Canada have on cardiovascular events (exenatide (trade names Bydureon and Byetta) and dulaglutide (trade name Trulicity)) - these studies are still underway.


Disclaimer: I am involved in research trials of semaglutide for type 2 diabetes and obesity.  I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk). 

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www.drsue.ca © 2016

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Bariatric Surgery For Type 1 Diabetes?

In parallel with the obesity epidemic in our general society, so too do many type 1 diabetics struggle with excess weight.  I am often asked whether patients with type 1 diabetes could benefit from bariatric surgery.

First, a review on the difference between Type 1 vs Type 2 diabetes:

• Type 1 diabetes is an autoimmune condition, where the immune system mounts a response against the pancreas, causing the pancreas to stop producing insulin.  Type 1 diabetics require insulin as treatment.
• Type 2 diabetes is a condition where the body is resistant to the effects of insulin.  This means that the pancreas has to work harder to make enough insulin to put sugar into cells for use as energy.  Over time, the overworked pancreas gets tired, its ability to produce enough insulin to control blood sugars declines, and diabetes develops. Some Type 2 diabetics are treated with lifestyle modification alone, some with pills or injectable medication, and some require insulin because their pancreas is too tired to make the insulin they need.

About 10% of diabetics have type 1 diabetes, and 90% have type 2 diabetes.  Traditionally, we used to think of type 1 diabetes being the kind of diabetes that has onset in thin kids or young adults, and type 2 diabetes as having onset in people with obesity later in life.  It turns out that type 2 diabetes can come on in childhood (the youngest type 2 diabetic recorded in Canada was 5 years old at diagnosis), and type 1 diabetes can sometimes have onset later in life.  Some people with type 2 diabetes have an ideal body weight, and some people with type 1 diabetes struggle with obesity.

There is lots of evidence to support the efficacy of bariatric surgery (especially gastric bypass surgery and sleeve gastrectomy) to improve control of type 2 diabetes, or even send it into remission (meaning the type 2 diabetes goes away - though it may reoccur later).

For type 1 diabetes, there is very little data.  However, a recent review summarizes the literature available for us, and what it found is that while bariatric surgery can be of benefit to help people with type 1 diabetes lose weight and reduce risk factors for heart disease, diabetes control does not seem to improve overall.

So, while bariatric surgery can be an appropriate treatment strategy for type 2 diabetes in people who struggle with obesity, the evidence does not support it for the improvement of diabetes control in type 1 diabetes.

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www.drsue.ca © 2016

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World Health Day - Eyes On Diabetes

Today is the World Health Organization's World Health Day, and for the first time, the focus is on Diabetes and its global impact.

In Canada, it is estimated that 11 million Canadians are living with diabetes or prediabetes, with 20 Canadians being diagnosed with diabetes every hour.

As per the press release from the Canadian Diabetes Association:

Diabetes increases a person’s risk for many serious complications such as heart attack, stroke, kidney failure leading to dialysis, and blindness. Nevertheless, for many people it is possible to live a healthy, full life with diabetes.

“People with diabetes play a critical role in ensuring the best health outcomes with the disease. Working closely with their health-care team, they manage blood sugar levels, foot care, eye care, physical activity and healthy eating,” says Dr. Jan Hux, chief science officer at the Canadian Diabetes Association (CDA). “Self-management is the cornerstone of diabetes care and people affected by it need the knowledge and skills to properly manage diabetes.”

According to the CDA’s Report on Diabetes: Driving Change, access to diabetes education is vital for learning more about nutrition, physical activity, blood sugar monitoring, medication and ways to make even little changes that can lead to success.

Some tips to keep on top of your diabetes include: taking action to learn as much as possible and using diabetes programs and services when needed; setting your targets and goals to maintain optimal average (A1C) and daily blood sugar levels; performing self-checks for foot problems; and scheduling regular eye exams. For more information, visit diabetes.ca/takecharge. 

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www.drsue.ca © 2016

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Liraglutide Reduces Heart Disease In People with Type 2 Diabetes

BIG news in the diabetes world was released on Friday - for the first time, a medication in the class called GLP-1 receptor agonists, called liraglutide (trade name Victoza), has been shown to reduce cardiovascular events in people with type 2 diabetes.

The LEADER trial enrolled over 9000 people with type 2 diabetes, who were at high risk of cardiovascular disease, and randomized them to receive either Victoza vs placebo with usual standard of care.

They found that Victoza was better than placebo to reduce the combination of death from cardiovascular disease, non-fatal heart attack and non-fatal stroke. A reduction in all three of these components contributed to the benefit that was seen.   The numbers and details are not yet available - we'll have to wait until the American Diabetes Association meeting in June to find out more.

Here's why this is ground-breaking news: 

We have long been uncertain whether we are actually preventing cardiovascular disease by treating diabetes - we know that the higher sugars are, the higher the risk of heart disease, but it has been evasive to actually prove that lowering blood sugars prevents heart disease. The next question is whether some medications to treat type 2 diabetes could be better (or worse) than others to protect from heart disease.  LEADER has now shown us that treating type 2 diabetes with liraglutide does indeed protect patients from cardiovascular events.

Within the GLP1 receptor agonist group of medications, a study of lixisenatide (called the ELIXA study) showed that it did not increase the risk of cardiovascular events, but it didn't prevent them either.  Studies of the other GLP1 receptor agonists available are currently underway.

As far as other type 2 diabetes medications go, the only other medication that has clearly been shown to reduce cardiovascular disease is empagliflozin, which you can read more about here and here.  Metformin, which is the #1 treatment advised for type 2 diabetes worldwide, has some weak evidence that it prevents cardiovascular events as well.

We will be waiting in anticipation for more details from the LEADER trial in June!


Disclaimer: I have been involved in research trials of liraglutide.  I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk). I am involved in research of medications similar to liraglutide for the treatment of type 2 diabetes.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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The Legacy Effect 30 Years Later - Good Control of Diabetes Prevents Heart Disease

A lot of people with diabetes wonder why their doctors and diabetes educators are seemingly obsessed with keeping blood sugars as close to normal as we can.  After all, blood sugars that are only mildly elevated usually don't come with much in the way of symptoms.

The point to keeping sugars as well controlled as possible is to prevent complications of diabetes developing over time - this includes damage to the eyes, heart, kidneys, and nerves in the feet and elsewhere in the body.

And - a new paper published has now shown us that the benefit of good control of diabetes to prevent cardiovascular disease persists for at least thirty years!

The study, which was recently published in the journal Diabetes Care, evaluated patients 30 years after their initial participation in the famed (well, famous in the diabetes world anyway) DCCT trial.  This was a clinical trial that enrolled 1,441 patients with type 1 diabetes, and assigned them to receive either more intense, or less intense, control of their blood sugars for a mean of 6.5 years.

During the 30 years of follow up, they found that the people who were in the tightly controlled group 30 years previously had a 30% reduction in the risk of developing cardiovascular disease, and a 32% reduction in the likelihood of having a heart attack, stroke, or dying from a cardiovascular cause, compared to those who were in the less tightly controlled group.  The tighter blood sugar control during the time of the original 6.5 year study was statistically responsible for all of the difference in cardiovascular disease between the two groups.

This data really impresses upon us the power of what we call the 'legacy effect' - good control of diabetes early on prevents complications later in life.  (Note: there is a similar trial in type 2 diabetics called the UKPDS study, which also showed that the legacy effect exists 10 years later.)

I think it is challenging for anyone to look forward 30 years into the future, and think about the importance of what we are doing now to our future self.  If you think about it, we actually spend a lot of our lives planning for our 30+ year future self.  Take financial planning, for example - most of us structure our home purchases, savings structures, and investments with the goal of planning for the distant future.  As I see it, planning for our health in the future is no different - and for people with type 1 diabetes, we now have very long term data to back this up.

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www.drsue.ca © 2016

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Natural Remedy Star Fruit Causes Kidney Damage

It is often in my day that people tell me that they are taking natural remedies for any number of medical conditions - for aches and pains, diabetes, obesity, cancer prevention... the list goes on.  The thinking that often underlies the decision to take these remedies is that they are natural, so how could they possibly be harmful?

I worry about my patients taking natural or naturopathic products, because rigorous clinical trials are not done to show benefit, nor (most concerning) to understand potential harms.  So, when I came across two very serious case reports of kidney damage from the seemingly innocent star fruit, I wanted to share it to illustrate the potential dangers of natural remedies.

Star fruit comes from a tree native to India and southeast Asia.  In addition to eating them as a fruit (I've enjoyed them myself on occasion while traveling to these areas), they are also touted as a herbal remedy for various ailments (including diabetes) in these countries.

Recently, two cases of star fruit toxicity were published.  One case was that of a woman with type 2 diabetes who consumed 200 mL of star fruit juice (less than a cup) from six star fruits, which resulted in kidney failure due to an inflammatory reaction in the kidneys (acute interstitial nephritis) caused by the high oxalate content of star fruit.  Thankfully, with medical treatment, her kidneys recovered.

The second case was that of a man with a history of moderate kidney dysfunction, who developed kidney failure after eating four star fruits over four days.  Thankfully, he also recovered after about 2 weeks.

In addition, like the grapefruit, star fruit also inhibits a group of liver enzymes (cytochrome P450 isoforms) which are important for metabolism of medications such as statins (cholesterol medications).  This is why it is advised for patients on statins not to eat grapefruit - star fruit should be included in this counselling as well.

So, take these cases into consideration the next time you think about reaching for a herbal remedy - remember that we simply do not know enough about these remedies to know if they are safe.

As a patient, be sure to tell your doctor about any natural remedies you are taking.

As a health care professional - remember to ask.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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PREdiabetes May Cause Kidney Damage

In our quest to control blood sugars of people who have diabetes, one of the 'small blood vessel' complications of diabetes that we are trying to prevent is damage to the kidneys.  For people who have prediabetes, it has generally been thought that they do not have an increased risk of small vessel disease.  However, there is mounting evidence that prediabetes may in fact cause small vessel damage; a new study suggests that prediabetes may in fact cause kidney damage.

First, let's talk about what we mean when we say 'prediabetes'.  Diabetes and prediabetes are defined on the basis of how high blood sugars are.   Quite simply, prediabetic blood sugars are lower than diabetic range blood sugars, but higher than normal blood sugars.  For the exact blood sugar definitions in Canada, please see Table 2 (diabetes) and Table 4 (prediabetes) here.

A study suggesting that prediabetes causes kidney damage was published in the American Journal of Kidney Diseases.  The study was a prospective cohort study that followed 1,261 people without diabetes between the ages of 50-62 for a median time of 5.6 years.  Participants who had prediabetes at the start of the study were at nearly 2 times higher risk of having hyperfiltration (an early manifestation of diabetic kidney disease), and at 1.8 times higher risk of having higher-normal albumin levels in their urine, compared to those with normal blood sugars (albumin in the urine is also a diabetes-related kidney complication). These changes were seen independently of other risk factors such as blood pressure at baseline, and independent of changes in blood pressure medications.

That prediabetes can cause complications before diabetes develops has a profound impact, in that 1 in 4 Canadian adults has diabetes or prediabetes, with most of those being prediabetic.  (In USA, 44% of American adults have diabetes or prediabetes).  Most people with prediabetes do not know that they have this condition, as there are usually no symptoms of this condition.

While the notion that prediabetes can cause small blood vessel complications is relatively new, it is known that prediabetes (especially impaired glucose tolerance) are at a substantially higher risk of developing BIG vessel complications (eg heart disease).

Knowing that prediabetes can cause organ damage makes two things very clear:

1.  We need to be checking for prediabetes in people who are at risk; and

2.   We need to aggressively prevent and treat prediabetes.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2016

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