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Does Liraglutide Mimic The Vascular Benefits Of Gastric Bypass Surgery?

sharma-obesity-glp-1On the last day of the 8th Annual Obesity Symposium here in Norderstedt, Germany, Marco Bueter from the University of Zurich presented a fascinating series of studies (just published in Circulation), demonstrating the “weight-independent” benefits of gastric bypass surgery on endothelial function (using an animal model).

Besides showing that 8 days after bypass surgery rats with diet-induced obesity had higher plasma levels of bile acids and GLP-1, that were associated with improved endothelium-dependent relaxation, not seen in sham-operated weight matched controls, but also that these effects could be prevented by blocking GLP-1 receptors with exendin 9-39.

In contrast, similar effects to those seen on vascular function in bypass rats were seen in sham-operated rats treated for 8 days with the GLP-1 analogue, liraglutide, or as the authors describe it,

“liraglutide restored NO bioavailability and improved endothelium-dependent relaxations and HDL endothelium-protective properties, mimicking the effects of RYGB”

Together these studies suggest that GLP-1 may well play an important causal role in the improved vascular function seen in patients undergoing gastric bypass surgery.

These findings are all the more interesting as liraglutide has now been approved for obesity treatment in the USA, Canada and Europe.

While these data are certainly not enough to describe liraglutide as “surgery in a pen”, they are indeed promising in terms of potential benefits of this treatment that may well be weight independent.

All the more reason to anticipate the outcome of the ongoing LEADER trial, which is currently evaluating the effect of liraglutide treatment on cardiovascular outcomes in patients with type 2 diabetes.

@DrSharma
Norderstedt, Germany

Disclaimer: I have served as a paid consultant and speaker for Novo Nordisk, the maker of liraglutide.

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Re-Do Bariatric Surgery

sharma-obesity-laparoscopic-surgery5This week I am Co-Chairing and speaking at the 8. Annual Obesity Symposium hosted by the European Surgical Institute in Norderstedt, just outside of Hamburg, Germany.

As was pointed out, even in the best hands, 10 to 20% of patients undergoing bariatric surgery will “fail”, often prompting surgeons to reoperate.

As I write this post, I am watching live “re-do” surgery on a patient who had an open Mason vertical-banded gastroplasty in 1987 (remining us that bariatric surgery has been around far longer than many people think).

Listening to the surgeon (Dr. Bruno Dillemans, Bruges, Belgium) commenting on the operation, it is apparent (even to a non-surgeon like myself), that this kind of surgery can be most challenging.

With the vast increase in the number of patients undergoing bariatric surgery worldwide, it is easy to see that bariatric “re-do” surgery will pose a significant challenge down the road.

@DrSharma
Norderstedt, Germany

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Free Online Courses For Obesity Management

sharma-obesity-5as-booklet-coverOver the past few months, I have been working with mdBriefCase, a major provider of free online accredited continuing medical education, to produce interactive modules for obesity management.

The modules are aimed at practitioners working in primary care and pharmacists and align closely with the Canadian Obesity Network’s 5As of Obesity Management framework.

The accredited course (Mainpro M1 and MOC Section 1 or 3 credits) is available free of charge to all Canadian Health Professionals.

To access the course for physicians and allied health practitioners on mdBriefCase – click here

To access the course for pharmacists on rxBriefCase – click here

@DrSharma
Hamburg, Germany

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MetAP2 Inhibitor Beloranib Produces Weight Loss in “Simple” Obesity

sharma-obesity-insulin-injectionReaders may recall a previous post on the remarkable efficacy of beloranib, a methionine aminopeptidase 2 (MetAP2 ) inhibitor, in patients with hypothalamic obesity.

Now, a paper by Dennis Kim and colleagues present the results of a phase II study in individuals with “simple” obesity, published in Diabetes, Obesity and Metabolism.

The study included 147 participants with moderate obesity, who were randomised to 0.6, 1.2, and 2.4 mg beloranib or placebo for 12 weeks, with no specific diet or exercise recommendations.

At 12 weeks, participants had on average lost between 5.5 and 10.9 Kg in a dose-dependent fashion.

This reduction in body weight was associated with relevant improvements in waist circumference, lipids and blood pressure.

Adverse effects included dose-dependent increase in sleep latency and mild to moderate gastrointestinal symptoms.

Beloranib is an investigational weight loss therapy with a novel mechanism of action. This study assessed the efficacy, safety, and tolerability of beloranib treatment for obesity.

This is certainly a most remarkable degree of weight loss seen at 12 weeks and it will be interesting to see the results of the longer-term studies that are currently underway.

@DrSharma
Edmonton, AB

Disclaimer: I have received consulting honararia from Zafgen, the maker of belanorib.

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Accuracy of Forearm Blood Pressure Measurements in Severe Obesity

forearm bp measurementGetting reliable blood pressure readings in patients with obesity can pose a problem, even when extra-large cuffs are available. An often discussed alternative is the use of forearm readings using a regular cuff, but the reliability of these readings remains unknown.

Now a study by Marie-Eve Leblanc and colleagues from the University of Laval, Quebec, Canada, published in Blood Pressure Monitoring, shows that forearm measurements with an oscillometric device can be reliably measured and are highly predictive of intra-arterial blood pressure measurements in patients with sever obesity.

The study involved 25 participants with an average BMI of 50.9kg/m2. Overall, sensitivity (0.98) and predictive values (0.93) for the presence of systemic hypertension were excellent, indicating that the forearm approach is a promising alternative to systemic hypertension diagnosis in severe obesity.

This may well simplify blood pressure measurements in patients presenting with severe obesity, where upper arm measurements may be difficult.

@DrSharma
Calgary, AB

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