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New Obesity Medication Approved In Canada

>> Monday, February 19, 2018





Last week, Health Canada approved a new medication for weight management in Canada. This medication is actually a combination of two medications that have been around for years, called naltrexone and bupropion.

Bupropion is an antidepressant medication (called Wellbutrin), and is also used as a smoking cessation agent (called Zyban). It works by stimulating the fullness center of our brains, thereby suppressing appetite (specifically, it increases POMC activity in the hypothalamus by inhibiting reuptake of dopamine and norepinephrine).

Naltrexone is an opioid antagonist, which has been used for many years in the treatment of alcohol dependence and prevention of relapse to opioid dependence.  Naltrexone works by preventing the fullness center of our brains from shutting itself off, further contributing to appetite suppression (specifically: POMC releases B endorphin that creates a negative feedback loop by binding to the mu opioid receptor on POMC neurons; naltrexone blocks this negative feedback loop). 

Naltrexone and bupropion are also thought to have an effect on the mesolimbic reward center of our brains as well, which may result in decreased motivation for, desire for, and sense of reward/satisfaction from tasty foods. 

The weight loss at 1year with naltrexone/bupropion (trade name is Contrave) is about 4% of body weight compared to placebo, with people continuing to take the medication through a year (i.e. excluding those who dropped out of the study) losing 8.1% body weight in combination with lifestyle modification.  With an intensive weekly behavioural modification program, people who continued the medication and lifestyle program lost 11.5% weight after a year, again about 4% more than the behavioral modification group alone, who lost 7.3% body weight.

In a study of people with type 2 diabetes, overall weight loss was 3.7% body weight (5.9% in those who completed the trial) vs 1.7% in the placebo group (2.2% in trial completers). In addition, diabetes control improved, with a 0.5% greater reduction in hemoglobin A1C (a diabetes report card test) than placebo.

The dose of naltrexone/bupropion for weight management is gradually escalated from the starting dose of one 8mg/90mg tablet once a day, to the full dose of two tablets twice per day, over about 4 weeks.

The most common side effects of naltrexone/bupropion are nausea (in 32% of people vs 7% on placebo), constipation, dizziness, vomiting, and dry mouth.  Gastrointestinal side effects tend to abate after about 4 weeks on treatment.

In terms of rare but serious side effects, there is a slightly increased risk of seizures with bupropion (0.1% of people in the weight loss studies vs 0% on placebo), so this medication should not be used in people at risk of seizures.   It is advised not to take Contrave with a high fat meal, as this increases absorption of the medication to more than what was intended.  Also, if doses are missed, they should not be taken later (just skip it completely).

Though it is an antidepression medication, bupropion can temporarily worsen depression or suicidal thoughts (there were no suicide attempts in any of the naltrexone/bupropion weight loss studies).

Contrave should not be used in people who are on opioid pain medications.  There are also a number of other potential medication interactions that must be assessed before starting the medication.

Heart rate and blood pressure can increase slightly; what is usually seen is actually a very small decrease in blood pressure with the weight loss, but not as much blood pressure decrease as one would usually expect with the amount of weight loss seen.  A cardiovascular safety trial was begun but halted about halfway through because interim data had been released, with the concern being that this data release could impact the integrity of that trial.  Naltrexone/bupropion appeared to have cardiovascular safety at the halfway mark, but this is not sufficient data to answer the question – thus, another cardiovascular safety trial is being planned.

Note that this is not a comprehensive list of all considerations in prescribing naltrexone/bupropion – the full Canadian product monograph is available here

Naltrexone/bupropion was approved in USA in 2014 - interested readers can consult the American product monograph here.  

It is encouraging that we now have three medications in Canada that are approved for weight management.  We know that obesity is very heterogeneous (different in causes, contributors, and health consequences from person to person), and thus, the best approach will be unique to each individual.  We also know that the response to antiobesity medication differs from person to person.  The general principle is that a 5% weight loss after 3 months on treatment is the best predictor of long term success with a particular medication (though in my opinion,  maintaining weight after a significant dietary-induced weight loss with the help of medication is an important success as well).  


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018



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Exactly How Does Diabetes Medication Empagliflozin Save Lives?

>> Monday, February 12, 2018




The diabetes world was stunned and delighted in 2015 when the diabetes medication empagliflozin (Jardiance) was proven to reduce cardiovascular death by a whopping 38%.   This was an unexpected finding, as no diabetes medication had ever before been shown to decrease the risk of cardiovascular events.  The protective ability of empagliflozin starts very early, suggesting that it is not an effect on atherosclerosis (hardening of the arteries) per se, as this process takes a longer time. It has been a puzzle to understand exactly what is behind the protective abilities of empagliflozin.

A recent publication by Inzucchi and colleagues describes an analysis of the EMPA REG data to try to shed some light on this interesting question.  They conducted an exploratory mediation analysis, examining many different variables, to see which ones contributed to the CV event reduction.

They found that changes in hematocrit and hemoglobin mediated about half of the benefit of empagliflozin.  (This may be because a higher hematocrit means that there is less plasma volume, and/or increased oxygen delivery to the heart.)  Smaller mediation effects were seen for uric acid levels, fasting blood sugar, and A1C (a diabetes ‘report card’ blood test).   The combination of hematocrit, fasting blood sugar, uric acid, and protein in the urine (urine albumin:creatinine ratio) mediated most of the beneficial effect of empaglifozin.

So, we learn what we suspected - that there are multiple and complex mechanisms at play by which empagliflozin reduces cardiovascular risk. There may well be additional mechanisms at play that were not measured, or measurable, in the EMPA REG study.

Empagliflozin was the first type 2 diabetes medication that was shown to decrease the risk of cardiovascular events.  Its cousin in this class called SGLT2 inhibitors, canagliflozin (Invokana), has also been shown to protect against cardiovascular events, but canaglifozin was also found to increase the risk of amputations and bone fracture.  Two medications of a different class (GLP1 receptor agonists), called liraglutide (Victoza) and semaglutide (Ozempic) also have a protective benefit.


Disclaimer: I receive honoraria as as continuing medical education speaker and consultant from the makers of empagliflozin (Boehringer-Ingelheim and Eli Lilly), canagliflozin (Janssen), liraglutide and semaglutide (Novo Nordisk).  I am involved in research of SGLT2 inhibitors and GLP1 receptor agonists as treatments for diabetes. 


Follow me on twitter! @drsuepedersen


www.drsue.ca © 2018


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Ketogenic Diet - Controversies

>> Monday, February 5, 2018






Last week, the Journal of the American Medical Association (JAMA) was rather aggressively promoting an opinion article about the ketogenic diet.  I know I'm getting into some rather controversial waters here, but I feel it is important to point out some concerns that I have about this article.

A ketogenic diet is an eating plan that restricts carbohydrates to a maximum of 20-50g per day (which is very low), which causes the body to burn fat as fuel instead.  The liver converts fatty acids to ketone bodies, which serve as an energy source.  There is often a reduction in hunger on this diet, and perhaps less reduction in energy burn with weight loss.

In support of the ketogenic diet, the first piece of science that the JAMA article discusses is a meta analysis of 13 randomized controlled trials that suggested that more people lose weight and keep it off on a ketogenic diet than people on low fat diets.

A reality check on this analysis: The difference in weight between these two groups was only 0.9kg (2 lb) at one year, and when they analyzed the four studies that continued out to 2 years, there was no difference in weight between the groups at all.

The JAMA article also comments on improvements in several metabolic parameters - but in the meta analysis, the only thing that was significantly different at 2 years was a small improvement in good cholesterol (HDL).

The article goes on to discuss the potential benefits of the ketogenic diet to people with type 2 diabetes.  I am very glad to see that they point out that medications like insulin and some oral medications for diabetes can cause low blood sugars, and have to be adjusted to avoid low blood sugars.

However, nowhere do I see mention of safety issues for people on SGLT2 inhibitors [canagliflozin (Invokana), dapagliflozin (Forxiga), empagliflozin (Jardiance)] - as blogged previously, there is a low risk of diabetic ketoacidosis (DKA) with these medications, and that risk could be increased on the ketogenic diet.   Some people with type 2 diabetes who require multiple doses of insulin per day may also have quite low to absent insulin production of their own, which could be a recipe to increase the risk of DKA on the ketogenic diet.

My third concern about this article is that it suggests that the lifestyle change to a ketogenic diet may not need to be permanent, and that some people may be able to add back a limited amount of carbs.  To me, this encouragement goes against the foundation of long term successful weight management - that lifestyle changes made to manage weight should be permanent changes that can be sustained lifelong. I'm concerned that this opens the door to the yo-yo weight pattern that is consequent to trying a diet plan that is not permanent nor sustainable for many.   

Finally, they include an image of coconut oil in their article. Seriously?  As blogged previously, coconut oil is actually one of the least healthy oils you can eat.

I do appreciate that the ketogenic diet can work for some people. Avoiding carbs helps to avoid a lot of the unhealthy and quick-grab food that permeates our society, from muffins to burgers to snacks at the grocery store checkout. 

We also know that what will work for one person is very different from the next.  So while the meta analysis shows no difference in weight on the ketogenic vs low fat diet at 2 years, there will be people within each of these groups who had success, and others who did not.

I also appreciate that the authors of the JAMA article note that "this is not a do-it-yourself-diet" for both safety and efficacy reasons. 

But I do feel that their review of the ketogenic diet is overly optimistic, misses some important safety concerns in people with type 2 diabetes, and gives inappropriate hope that this diet can be a non-permanent approach, when no lifestyle change that is not permanent is unlikely to result in sustained success over the long term.

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018




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Could Your Cholesterol Medication Cause Diabetes?

>> Monday, January 29, 2018




With any medication, there are benefits and risks that need to be considered.  Medications are generally recommended to a patient when the potential benefit of the medication is felt to be greater than the potential risks.

While it is extremely important for both doctors and patients to be well informed of potential side effects of medications, the media unfortunately loves to hype up side effects, often making it seem like the risks of taking a medication must outweigh any potential benefits.

Statins, a group of cholesterol medications, have taken a particular beating in the media over the years.   A colleague of mine approached me not too long ago saying that he was worried about his patients being afraid of taking their statin cholesterol medications because of fear of developing diabetes as a side effect, and asked me if I would publish a post on this topic.

An excellent review was published in The Lancet, which does a great job of addressing the question of benefit vs risk of statin therapy.

If 10,000 people are treated with statin therapy for 5 years: (with the example given of 40mg of atorvastatin (Lipitor) daily)

Benefits:
  • if these 10,000 people had a past history of 'blocked arteries' (occlusive vascular disease) - eg prior heart attack or stroke: 1,000 would be saved from another heart attack or stroke
  • if these 10,000 people had no history of vascular disease: 500 would be saved from a heart attack or stroke

Risks: 
  • 50-100 will develop diabetes because of their statin
  • 5-10 will have a bleeding type (hemorrhagic) stroke
  • 5 will develop serious muscle complications


The risk of developing diabetes due to statin medications is higher with the more powerful statins (atorvastatin (Lipitor) and rosuvastatin (Crestor)), and with higher doses.  However, it is precisely these particular statins at the higher doses that have the biggest benefit to prevent heart attacks and strokes in people who have a past history of vascular disease.

People with risk factors for developing diabetes (eg, prediabetes, obesity) are at higher risk of statins tipping them up into diabetes range blood sugars. However, even if a person develops diabetes due to their statin, the health benefit in preventing heart attacks and strokes is much greater than the adverse effect of diabetes on their health, provided the diabetes is well managed.

For people who already have diabetes, statins also have a powerful benefit in preventing heart attacks and strokes, which is felt to far outweigh any small increase in blood sugars that may occur (and can be managed with adjustment to diabetes medication).

As to how statins increase the risk of developing diabetes, another study in The Lancet suggests that it may be related to the mechanism of statins to inhibit an enzyme called HMG CoA reductase, and may be genetically mediated.


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018



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Is Your Doctor NOT Talking Nutrition?

>> Monday, January 22, 2018




Everyone out there: I would like you to raise your hand if your doctor has NOT recently talked to you about good nutrition.  If you have your hand up, you are not alone - only about 12% of office visits include counselling about diet, despite there almost always being a good reason to talk about nutrition (eg diabetes, obesity, high blood pressure, and so forth).

Doctors out there - do you feel like you don't do a great job in counselling your patients on good nutrition?   If so, you are definitely not alone.

A recent Viewpoint paper published in the Journal of the American Medical Association uncovers some important issues that limit good nutritional counselling in the doctor's office.

Issues cited that limit doctors in providing nutritional counselling:
  • Doctors receive very little nutritional training in medical school. 
  • Limitations of time in an appointment. 
  • Limitations in reimbursement (pay) for doctors to provide nutrition counselling.
  • Frustration in trying to counsel on healthy food choices when our environment is so full of unhealthy choices.
Here are some easy steps that clinicians can take to improve nutritional counselling: 

1. Start the conversation - check out this easy to use tool, which contains eight quick and easy questions you can ask, with suggestions for reasonable changes that you could recommend. 

2.  Use the 5As of Obesity to help start a conversation when you note that your patient carries excess weight. 

3.  Focus on small steps - use the tool for suggestions. 

4.  Don't do it alone (if possible) - nutrition counselling and weight management require multidisciplinary support!  Engage any support you have to help provide your patient the help they need from various avenues: dietitian, nutritionist, psychologist, health/weight management classes - anything you can find to provide your patient with lots of health care provider time to guide them through their journey. 


Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018













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A HEARTFELT WELCOME!

I am excited that you have arrived at my site, and I hope you are too - consider this the first step towards a Healthier New You!! As a medical doctor, Endocrinologist, and obesity specialist, I am absolutely passionate about helping people with weight management. Though there is certainly no magic cure for obesity, there IS a successful treatment plan out there for you - it is all about understanding the elements that contribute to your personal weight struggle, and then finding the treatment plan that suits your needs and your lifestyle. The way to finding your personal solution is to learn as much as you can about obesity: how our toxic environment has shaped us into an overweight society; the diversity of contributors to obesity; and what the treatment options out there are really all about. Knowledge Is Power!!


Are you ready to change your life? Let's begin our journey together, towards a healthier, happier you!!




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