Liraglutide, a GLP-1 analogue now available for the treatment of obesity (as Saxenda) in North America, works by reducing appetite and increasing satiety, thus making it easier to lose weight and keep it off (with continuing treatment).
Now, a study by Olivia Farr and colleagues, in a paper published in Diabetologia not only present data showing the presence of GLP-1 receptors in human cortex, hypothalamus and medulla, but also provide functional evidence for altered brain response to food cues.
After documenting the presence of GLP-1 receptor in human brains using immunohistochemistry, the researchers conducted a randomised controlled placebo-controlled, double-blind, crossover trial in 18 individuals with type 2 diabetes who were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days, and 1.8 mg for 3 days).
Using functional MRI neuroimaging studies, the researchers found that liraglutide remarkably decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images.
They also observed decreased activation in the insula and putamen, areas involved in the reward system.
Furthermore, using neurocognitive testing, the researchers showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide.
In contrast, ratings of nausea (a well-known side effect of liraglutide) correlated with decreased brain activation.
As the authors note,
“Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss.”
These findings no doubt match the reports from my own patients of experiencing less interest in highly palatable foods and finding it much easier to pass up on foods that they would have otherwise found hard to resist.
Clearly, as we learn more about brain function in eating behaviour, we are thankfully moving towards treatments that are clearly proving to be far more effective than just telling patients to “simply eat less” (which I have often likened to telling people with depression to “simply cheer up”).
Disclaimer: I have received honoraria for speaking and consulting from Novo Nordisk, the maker of liraglutide
While the often impressive benefits of bariatric surgery on health and quality of life in younger patients with severe obesity are well documented, the safety and benefits of bariatric surgery in older patients remains largely unclear.
Now, a systematic review by my colleague Alexandra Chow from the University of Alberta, Edmonton, Canada, published in Obesity Surgery looks at outcomes in patients older than 65 years of age.
The review includes data from 8 studies (1835 patients) of roux-en-Y gastric bypass surgery, all of which were case series.
Overall mean excess weight loss was about 70%, which is only marginally less than generally seen in younger patients with this procedure.
Mean 30-day mortality was 0.14 % with a post-operative complication rate of around 20%, with wound infections being the most common (8 %) followed by cardiorespiratory complications (3 %).
Thus, it appears that bariatric surgery is reasonably safe and produces meaningful clinical outcomes in patients beyond 65 years of age.
Obviously, I would assume that these numbers are better than expected as centres (including ours) are rather selective about patients as they get older. Thus, these outcomes may not be applicable to every patient above the age of 65.
Nevertheless, it appears that for selected elderly patients, bariatric surgery may well be considered an effective treatment for severe obesity despite a reasonable measure of risk.
The GLP-1 analogue liraglutide (Saxenda), recently launched in North America for the treatment of obesity, has now also been shown to improve symptoms (apnea-hypopnea index – AHI) of obstructive sleep apnea (OSA).
This, according to a paper by Blackman and colleagues published in the International Journal of Obesity.
This 32-week randomized, double-blind trial was conducted in about 360 non-diabetic participants with obesity who had moderate (AHI 15-29.9 events/h) or severe (AHI ⩾30 events/h) OSA and were unwilling/unable to use continuous positive airway pressure therapy (CPAP).
After 32 weeks, the mean reduction in AHI was greater with liraglutide (3.0 mg) than with placebo (-12.2 vs -6.1 events/h).
This improvement in sleep apnea was largely explained by the greater mean percentage weight loss compared with placebo (-5.7 vs -1.6%).
Additional findings included a greater reductions in HbA1c and systolic blood pressure in the participants treated with liraglutide versus placebo.
Liraglutide was generally well tolerated with no unexpected adverse effects.
Thus, it appears that in addition to weight loss, treatment with liraglutide 3.0 mg results in clinically meaningful improvements in the severity of obstructive sleep apnea, an important issue that affects both the cardiometabolic risk and quality of life of so many individuals living with obesity.
Disclaimer: I have received honoraria as a consultant and speaker for Novo Nordisk, the maker of liraglutide
When adjustable gastric banding was first introduced as a treatment for severe obesity, it was touted not only as a surgically simple procedure (which it is) but also as having the advantage of being “reversible”.
Unfortunately, as many patients who have had bands implanted only to discover that they either did not work or created all kinds of other problems, “simply” removing the band was often anything but “simple”.
Moreover, as with any obesity treatment, removing the band (or in other words, stopping the treatment) virtually guarantees weight regain, leaving the patients often back to where they were (if not worse off) than before the operation.
In reality this means that when bands need to be removed, they often have to be followed by a more definitive procedure like a sleeve gastrectomy (SG) or a Roux-en-Y gastric bypass (RYGB) (the operations that should probably have been done in the first place).
The debate that continues to rage between surgeons, is whether or not it is safer to remove the band and do the more definitive operation within a single procedure or in two separate operations.
Now my colleague Jerry Dang from the University of Alberta, Edmonton, Canada, has published a systematic review and meta-analysis of the two approaches in Obesity Surgery.
According to their analysis of 11 studies that included 1370 patients, there was no difference in the rates of complications, morbidity, or mortality between one-step and two-step revisions for both RYGB and SG groups.
Thus, the authors conclude that both immediate or delayed revisional bariatric surgeries are reasonable and comparable options for band revisions.
Overall however, this should not distract from the fact that a band removal in itself can be a difficult operation with its own set of complications and given the number of bands that have to be removed, it may be best be recommended that preference be given to doing an SG or RYGB as the primary procedure.
Fortunately, this is indeed proving to be the practice at an increasing number of surgical centres.
Although metabolic benefits are often presented as one of the key benefits of bariatric surgery, in my experience, the benefits to patients in terms of less pain and mobility have always been far more impressive.
Now, a study by Wendy King and colleagues, published in JAMA, confirms these clinical observations in a large cohort of patients undergoing bariatric surgery for severe obesity.
The researchers looked at data from the Longitudinal Assessment of Bariatric Surgery, an ongoing observational cohort study at 10 US hospitals.
Based on results of 2221 participants (89% women, median BMI 46, median age 47), bariatric surgery at 1 year post surgery resulted in a clinically meaningful improvement in 60% of participants for pain, 75% for physical function, and 60% for walk time.
These improvements were largely related to significant reduction in disability related to knee and hip pain.
Nevertheless, the researchers also found that between year 1 and year 3, rates of improvement significantly decreased to 50% for pain and to 70% for physical function, although improvement rates for walk time, knee and hip pain, and knee and hip function were largely sustained.
Variables that appeared to increase the chances of post-surgical benefits included younger age, male sex, higher income, lower BMI, and fewer depressive symptoms presurgery; no diabetes and no venous edema with ulcerations postsurgery (either no history or remission); and presurgery-to-postsurgery reductions in weight and depressive symptoms.
Given that (in contrast to metabolic problems) there are few effective medical treatments for pain and mobility, these “benefits” of bariatric surgery certainly warrant greater attention as it is often these (and not the metabolic problems) that determine the often poor quality of life associated with severe obesity.