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Semaglutide - New Diabetes Medication With Superior Diabetes Control And Weight Loss - Now Approved In Canada

>> Saturday, January 13, 2018





In the current era of type 2 diabetes, we are fortunate to have many different medications to choose from to help people control their blood sugars, choosing the medication(s) that fit each individual's unique health situation best.   In the last decade or so, we have developed diabetes medications that can avoid two unwanted side effects of some of the older diabetes medications: weight gain (with some causing weight loss), and low blood sugars.

Health Canada has just approved a new medication, called semaglutide, which is not only superior to any other medication it has been tested against for blood sugar control, but also causes more weight loss than any other medication on the market.

Semaglutide (trade name Ozempic) is a GLP1 receptor agonist, which works by stimulating the pancreas to increase insulin release and suppress the production of a hormone called glucagon, and also acts as an appetite suppressant in the hunger/fullness centre of the brain.  It is a once weekly treatment given by injection under the skin.  It reduces hemoglobin A1C (the diabetes report card) by up to 1.8%, and reduces weight in people with diabetes by up to 6.4 kg (14 lb) in the clinical trials that have been conducted.

In terms of side effects, like other GLP1 receptor agonists that are already available (including liraglutide (Victoza), dulaglutide (Trulicity) and exenatide (Bydureon or Byetta), it temporarily slows down stomach emptying, so can cause nausea, constipation, or diarrhea, which usually goes away after a few weeks, if it occurs.  Also similar to other GLP1s, there is a low risk of pancreatitis.

Unique to semaglutide, there was an increase in diabetic eye complications seen in the largest clinical trial (in which I was an investigator) , which is thought to be due to the power of semaglutide to greatly improve diabetes control (we have seen occasional temporary worsening of diabetic eye disease in studies of other medications, including insulin, when there is a big and rapid drop in blood sugars).  This risk is higher in people with existing diabetes eye complications.  However, long term improvement in diabetes control decrease the risk of diabetes eye complications overall.

Semaglutide has also been shown to reduce the risk of cardiovascular events in people with type 2 diabetes and cardiovascular disease - now the fourth diabetes medication available in Canada to show this benefit.  The full product monograph, with a full description of clinical trials and potential side effects, is available here.

Semaglutide is currently being studied as an obesity treatment as well, in people without diabetes, but is not yet approved for this indication.


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 semaglutide (Novo Nordisk). 

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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Does Earlier Menopause Mean A Higher Risk Of Diabetes?

>> Sunday, November 19, 2017



Menopause is a major life transition for women, both psychologically and physiologically.  A number of changes occur in a woman's body that alters metabolism, unfortunately tipping the scales towards an increase in cardiovascular risk.  We know that an earlier age of menopause increases the risk of cardiovascular disease, and that a later age of menopause onset seems to be protective.

Whether earlier age of menopause increases the risk of developing type 2 diabetes has been somewhat controversial; a new study sheds additional light on this question.

The study, published in the journal Diabetologia, evaluated 3639 postmenopausal women from the population based Rotterdam study.  They followed these women for a median of 9.2 years, with the goal of assessing how the risk of developing type 2 diabetes may vary depending on the age of menopause.

They found that the risk for developing type 2 diabetes, compared to women with late menopause (at more than 55 years old), is:

  • 3.7 times higher for women with premature menopause (at less than 40 years old)
  • 2.4 times higher for women with early menopause (at 40-44 years old)
  • 1.6 times higher for women with normal age of menopause (at 45-55 years old)
They found that for every year later that menopause occurred, the risk of developing diabetes decreased by 4%.

So why would the risk of diabetes go up with earlier menopause? With menopause comes a natural decrease in our reproductive hormones (estrogen, progesterone, and testosterone).   These changes promote a loss of muscle and an increase in fat, especially the visceral fat that sits around our abdomen and internal organs - this is the fat that has negative effects on our metabolism.  A loss of progesterone, and hot flashes from having lower estrogen levels, can impair sleep, which is a known risk factor for obesity and metabolic syndrome.  The emotional challenges of menopause may bring out an increase in emotional eating for some women, which can promote weight gain and increase diabetes risk as well.

Interestingly, this study looked at several reproductive hormone levels at the start of the study, and showed that earlier menopause was associated with an increase risk of diabetes, independent of these hormone levels, and also independent of body mass index at baseline or shared genetic factors.

The authors hypothesize that earlier menopause and type 2 diabetes may be a consequence of epigenetic changes, which are changes that alter the physical structure of our DNA.  Epigenetic changes can be caused by a number of factors, including poor diet, smoking, and many other environmental factors. 

Further studies need to be done looking at epigentic changes to determine if these may be responsible for the association between earlier menopause and diabetes risk. If epigentic changes are at play here, living well and healthily throughout life is more important than ever!

After menopause, we can combat cardiovascular and diabetes risk by:
  • Keeping active - engage those muscles! This helps to combat the decrease in muscle mass. 
  • Making healthy permanent lifestyle changes 
  • Having good sleep hygiene
  • Getting help from your doctor if you are struggling with menopausal symptoms.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2017

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Dexcom G5 Continuous Glucose Monitor - New Glucose Monitoring Technologies Part 2

>> Saturday, November 4, 2017

The traditional way of monitoring blood sugars is with finger pokes, but there are other newer technologies out there that make it not only easier to check, but provide more data as well.

Two new technologies have recently arrived in Canada: the Freestyle Libre (see last week's post on this), which is a poke free glucose monitor, and the Dexcom G5 continuous glucose monitor, which allows you to broadcast sugars wirelessly to family or caregivers.   This week, we’ll review the Dexcom G5.  

The Dexcom G5 is a continuous glucose monitor (CGM). This consists of a sensor that you apply to your abdomen (lasts 7 days) which measures glucose in the interstitial fluid that surrounds your cells under your skin, as an estimate of blood glucose levels.  There is a transmitter that fits onto the sensor (lasts 3 months), which transmits continuous sugar readings to the reader that comes with it.  It has alarms for low or high sugars.  It needs to be calibrated against finger poke readings every 12 hours, so while the CGM can decrease the number of finger pokes, it doesn’t eliminate them entirely.  

While CGMs are not new to Canada, the exciting new feature of this model is that it transmits glucose values not only to the reader, but also to smartphones, iPads, and some smart watches.  Also, the Dexcom5 has been approved in Canada and the USA for making treatment decisions (the previous model, the Dexcom G4, is not).  Though there have been reports of inaccuracies, the FDA concluded that 'the benefits of additional information gained from this device outweigh the inaccurate results, rates of change, and false negative and positive alarms and alerts'.  As far as the clinical trials go, the accuracy is reported to be within about 9% of actual blood sugar.  The cost is about $3100 per year (ouch!).

This can be a useful tool for parents (it’s approved down to age 2) or caregivers who want to keep an eye on their loved one’s sugars.  Also, CGMs with alarms have helped to keep many a patient of mine who have lost their ability to feel low blood sugars safer, waking them up at night when sugars are going low.   As for all of the interstitial glucose monitoring technologies - if in doubt about the glucose reading - check with a finger poke.


Follow me on twitter! @drsuepedersen



www.drsue.ca © 2017

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Poke Free Glucose Monitor Has Arrived In Canada! New Glucose Monitoring Technologies Part 1

>> Tuesday, October 31, 2017




The traditional way of monitoring blood sugars is with finger pokes, but there are other newer technologies out there that make it not only easier to check, but provide more data as well.

Two new technologies have recently arrived in Canada: the Freestyle Libre, which is a poke free glucose monitor, and the Dexcom5 continuous glucose monitor, which allows you to broadcast sugars wirelessly to family or caregivers.   Today, we’ll review the Libre, and I’ll follow up with a separate post on the Dexcom5.

Finger pokes are uncomfortable, and can be a barrier to checking blood sugars.  As blogged previously, the Freestyle Libre system (pictured above) is an entirely new technology, consisting of a tiny monofilament sensor that you apply to your arm every 14 days.  It measures glucose in the interstitial fluid that surrounds the cells under your skin, as an estimate of blood glucose levels. Hold the reader near the sensor and Ding! - it will tell you your current glucose level, which direction your sugar is heading (up, down, or steady), a message on the screen if glucose is going low or high, and – get this – it will show you your last 8 hours of glucose readings in a graph. 

The Libre sensor is calibrated right out of the box, so there is no need for finger poking to calibrate it.  It is approved by Health Canada for making treatment decisions, provided that you take into account all of the info on the screen when you scan the reader.

You DO need to check with a finger poke (built into the reader) if:

  • sugar reads low or going low (very important, as the Libre may inaccurately indicate hypoglycemia)
  • during a time of a rapid blood sugar change (for example during exercise, after eating, or after taking a bolus of insulin; the reason being because interstitial glucose changes lag behind blood glucose changes); or
  • if your symptoms do not agree with the number you see when you scan (remember, though, that some people with diabetes are not able to feel it when their sugars go low - in that case, confirming with a finger poke may be needed more often) 

It’s less accurate on the first day you wear it, so I would suggest more reliance on finger pokes on day 1.  The accuracy improves to within about 9-11% of actual blood sugar after that. (Standard finger poke monitors have varying accuracy, and the analysis method for accuracy is different, but Diabetes Canada accepts within 15% accuracy for those monitors.)   It costs about $50 for the reader (one time cost), and about $90 for each sensor (replaced every 14 days).  There is a built in ketone meter as well, which is handy if there is a need to check ketones (more on this here).

The Libre provides the opportunity to decrease the need for finger pokes, and scanning just 3 times a day (every 8 hours) is enough to give a full 24h glucose profile, which can help you and your diabetes care providers understand your blood sugars in even more detail.

Stay tuned for info on the Dexcom5 continuous glucose monitor!


Disclaimer: I have received honoraria as a continuing medical education speaker and consultant from the makers of the Freestyle Libre (Abbott).

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2017

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Anemia, Mortality, and Type 2 Diabetes

>> Thursday, October 19, 2017





Health care providers out there may have noticed that anemia is a not-infrequent finding amongst patients with type 2 diabetes.

It turns out that there are multiple reasons for anemia in type 2 diabetes - and the health consequences may be severe.

A study was recently published evaluating the prevalence, risk factors, and prognosis of anemia in two groups of Australian patients.  They found that the prevalence of anemia was double to triple in people with type 2 diabetes, compared to people without diabetes.

They found multiple risk factors independently associated with a higher risk of anemia, including:

  • impaired kidney function: related at least in part to reduced erythropoeitin production by the kidneys, which is a hormone that stimulates red blood cell production
  • longer duration of diabetes: 5% increased risk of anemia per year of having diabetes - may be due to decreased red blood cell production and/or increased destruction, as consequences of chronically elevated blood sugar
  • metformin use: likely related to vitamin B12 deficiency, but other mechanisms such as low magnesium are considered
  • thiazolidinedione use [pioglitazone (Actos) or rosiglitazone (Avandia)]: likely related to fluid retention
  • peripheral arterial disease: possibly related to higher oxidative stress, inflammation, atherosclerosis
Other risk factors were identified as well, such as low iron, and low testosterone in men.

After adjustment for other independent predictors of mortality, anemia was associated with a 57% increased risk of mortality over the mean of 4.3 years of study, compared to people with diabetes but without anemia.

The good news is that many of these risk factors for anemia are treatable, and even preventable.  For example: optimizing blood sugar control; checking vitamin B12 in people on metformin; checking iron levels in people who are anemic and investigating for the cause of low iron if so.


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2017

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How Successful is Gastric Bypass Surgery 12 Years Later?

>> Saturday, September 23, 2017



We know that gastric bypass surgery is a powerful tool in the management of obesity and metabolic syndrome.  However, there is not a lot of data available following patients out over the very long term.  A recent study is the first prospective study looking only at Roux-en-Y gastric bypass surgery, to give us data out as far as 12 years.

The study, published by Adams and colleagues in the New England Journal of Medicine, enrolled 418 patients in Utah, USA who underwent gastric bypass surgery, and compared them over the long term to 417 patients who wanted surgery but did not have surgery (primarily because of lack of financial insurance coverage), and a third group of 321 patients with obesity who were not interested in surgery. They had an excellent rate of follow up of over 90% of patients at 12 years.

Here are some of the key findings: (skip to take home messages below for the short version)

1.  Weight loss:
  • Two years after gastric bypass surgery, the mean weight loss was 45 kg. 
  • At 6 years postop, the mean weight loss was 36.3kg (so there was about 20% weight regain, which is very consistent across studies).
  • At 12 years postop, the mean weight loss was 35kg – so weight was overall stable from 6 years to 12 years after surgery.

 [At 12 years, people who wanted surgery but didn’t have it had lost 2.9 kg (probably because they were part of this study), and people with obesity who did not want surgery had lost 0 kg (also notable for no weight gain over the long term).]


2.  Type 2 diabetes:

Among patients in the surgery group who had type 2 diabetes before surgery:
  • At 2 years postop, 75% of diabetes had gone into remission.
  • At 6 years postop, 62% of diabetes cases were in remission
  • At 12 years postop, 51% of diabetes cases were in remission.
  • The likelihood of diabetes being in diabetes remission at 12 years was 8.9 times higher for those who had had surgery compared to those who wanted but did not get surgery, and 14.8 times higher than those who did not want surgery in the first place.
  • At 12 years, the likelihood of being in diabetes remission was highest in people who had diet controlled diabetes before surgery (remission rate 73%), less for people who needed pills to treat their diabetes before surgery (remission rate 56%), and lowest for people who required insulin to treat their diabetes before surgery (remission rate 16%). 
  • At 12 years, there was a 91-92% lower risk of having new type 2 diabetes develop in patients who had had bariatric surgery, compared to the non surgery groups.


3.  Mortality rates:

At 12 years, mortality in people who had gastric bypass surgery was lower than those who wanted surgery but didn’t get it, but there no different between those who had gastric bypass surgery than those who didn’t want surgery in the first place, likely because the group not wanting surgery was healthier at baseline. There were 5 suicides in the group that had bariatric surgery, compared to 2 suicides in the non surgical group.  (see here and here and here for discussion of suicide risk after bariatric surgery ) 


Take home messages from this study:
  • On average, weight loss is stable over the long term after gastric bypass surgery – though the results can be different for different people, and certainly lifelong dedication to permanent lifestyle changes are essential for continued success.

  • Gastric bypass surgery can be a powerful tool to not only put diabetes into remission, but also to decrease the risk of developing diabetes later on.  Earlier intervention is better, because the longer a person has diabetes, the more tired their pancreas gets (ie decreased beta cell function, which are the cells that produce insulin), and a tired pancreas may be too tired to control blood sugars after bariatric surgery without help from medication.  Thus, considering bariatric surgery early in the course of diabetes, or even in the prediabetes phase, may have the most powerful impact.


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www.drsue.ca © 2017

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Could Antacid Medications Affect Blood Sugar Control in Diabetes?

>> Saturday, August 5, 2017






Proton pump inhibitors (PPIs) are medications commonly prescribed to treat heartburn and peptic ulcer disease [eg omeprazole (Losec), pantoprazole (Pantoloc), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Pariet)].    Since PPIs work by blocking acid secretion in the stomach, and since a higher acid content of food lowers its glycemic index, I was asked whether PPIs could increase the effective glycemic index of a meal and thus have a negative impact on diabetes control.

It turns out that PPIs have a very interesting relationship with pancreatic function and blood sugars.

Firstly, as PPIs work by blocking acid secretion in the stomach,  PPIs do increase the pH in the stomach and very high up in the small intestine (proximal duodenum).  However, there is little to no effect on pH in the majority of the small intestine, where carbohydrates are absorbed.

PPIs raise serum levels of a hormone called gastrin, which is responsible for stimulating acid secretion in the stomach.  This is because the gastrin secreting cells in the stomach sense that acid production is low, so more gastrin gets cranked out in an attempt to increase acid secretion.

Interestingly, gastrin stimulates glucose-induced insulin secretion from the beta cells of the pancreas.  There is also some experimental evidence that gastrin may stimulate the production of new beta cells.   Further, PPIs slow emptying of the stomach, because less acid in the stomach means that it takes longer for solid food to be broken down and be ready to pass into the small intestine.

So, based on these mechanisms, it seems that PPIs could possibly have a benefit to blood sugar levels.  While the studies on this are still quite limited, the available evidence suggests that PPIs could lower A1C (a marker of diabetes control) by 0.5% to as much as 1% - possibly as much as a diabetes medication!

PPIs are medications that have benefits but also potential risks, including increased risk of gastrointestinal infections, malabsorption of important micronutrients like calcium, magnesium, vitamin B12, and iron, increased risk of fracture, changes in gut bacteria, and others (note this list is not exhaustive), and they should not be prescribed for the purpose of blood sugar control.

That being said, I will be watching blood sugar control with extra interest the next time one of my patients with diabetes is started on a PPI for their gastrointestinal issues.


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2017

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