Obesity Medication Lorcaserin Neutral For Cardiovascular Events

Lorcaserin (trade name Belviq) is an obesity medication that is not available in Canada, but is used in USA and other countries as a treatment of obesity.  A recent study evaluated the cardiovascular safety of lorcaserin in people with obesity or overweight, with either established cardiovascular (CV) disease, or multiple cardiovascular risk factors but without established CV disease. (skip to BOTTOM LINE below as to why this study is important)

In the study, published in the New England Journal of Medicine, 12,000 people were randomized to receive either lorcaserin or placebo for a median of 3.3 years.  Seventy-five percent of participants had established cardiovascular disease. At one year, people on lorcaserin lost -4.2kg, compared to -1.4kg in the placebo group.   At 3.3 years, there was no difference in the rate of cardiovascular events (a composite of cardiovascular death + nonfatal heart attack + nonfatal stroke) between groups, at 2.0% per year on lorcaserin vs 2.1% per year on placebo.

In people who had diabetes at the start of the study (57% of the total population), diabetes control was improved slightly at 1 year (-0.3% greater reduction in A1C than placebo).  Amongst those with prediabetes at the start, the proportion of people on lorcaserin who went on to develop type 2 diabetes was slightly lower (3.1% per year) than those on placebo (3.8% per year).

The rate of discontinuation of study medication was similar between the two groups, at 12.0% per year in the lorcaserin group vs 12.7% in the placebo group.  In the lorcaserin group, the most common side effects leading to stopping treatment were known potential side effects of dizziness, fatigue, headache, diarrhea, and nausea.

Echocardiogram (heart ultrasound) was performed in a subset of 3270 study participants, because an related obesity medication previously available (fentermine-phenfluramine or Fen-Phen) was found to have an adverse effect on heart valves.  After a year of treatment, they found no statistically significant difference in heart valve problems between the two groups, with 23 cases of new onset, mild aortic valve insufficiency on lorcaserin vs 15 on placebo, and 13 cases of pulmonary hypertension on lorcaserin vs 8 on placebo.

So what's the BOTTOM LINE?    This is the first time that the cardiovascular safety of an obesity medication has been rigorously tested and proven to be safe. Some previously available obesity medications have been pulled from most markets due to safety concerns (eg sibutramine due to increased cardiovascular events in people with CV disease, rimonabant due to psychiatric side effects).

Regarding the three currently available obesity medications in Canada:

• Orlistat (Xenical) has not been tested in this fashion 
• Liraglutide as a diabetes treatment (Victoza 1.8mg) has been shown to reduce cardiovascular events and death in people with type 2 diabetes.  Though liraglutide as an obesity treatment (Saxenda 3.0mg) has not been specifically studied for CV safety, these data are accepted by regulatory agencies as reassurance for CV safety in the lower risk population of people with obesity without diabetes
• Naltrexone/bupropion (Contrave) had a study started but stopped part way through because of a release of interim results that was felt to compromise the integrity of the study. A new trial is now in the planning stages. 

Looking very forward to more safety outcome data in this area.


Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of liraglutide (Novo Nordisk) and naltrexone/bupropion (Valeant).

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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2018 Diabetes Canada Guidelines Are Out!

The Diabetes Canada (formerly Canadian Diabetes Association) Guidelines are issued in full every 5 years.   As a coauthor of the Weight Management Chapter, I can tell you that these Guidelines have truly been a labor of love for all of us - more than two years with several rounds of evidence review, drafting, re-drafting as new data comes out.... and this is what makes our guidelines one of the most respected diabetes documents in the world!

The 2018 Guidelines are exciting, with a number of substantial changes from the 2013 edition in terms of approach, rigour of methodology, and recommendations.

Each chapter in the Guidelines is structured with a framework including:

Key Messages

Key Messages For People With Diabetes (this is new and awesome, and reflects that the Guidelines are intended not only for the use of health care providers, but also for people with diabetes)

Recommendations


Over the next weeks, I will be posting blogs highlighting some of the key points and changes to the guidelines, and I'll always include a link to the chapter itself if you'd like to read it in full.

Enjoy!

Follow me on twitter! @drsuepedersen

www.drsue.ca © 2018

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Ketogenic Diet Controversies

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?

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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