Obesity is a Chronic Disease
Over the last year I have had the pleasure of working on a number of obesity programs. Obesity is now viewed as a chronic, progressive disease state by most medical groups across the world. Clinicians have to start to treat obesity as a chronic disease versus just a lack of willpower.
There are currently three anti-obesity medications available in Canada and I thought I would do a quick review of the most commonly asked questions on these medications.
Key point: The European Obesity Guidelines recommend that when starting a patient on an anti-obesity medication, clinicians should evaluate the efficacy in 3 months. If the patient has lost 3-5% body weight, continue treatment (can be continued long-term), if not, consider stopping the medication as the patient is unlikely to respond.
Why use medications when the patient can just eat less and exercise more?
There is the widely held belief that people with obesity should just simply have better lifestyle to control their weight. In reality, very few people can achieve long-term weight control through just lifestyle changes alone. The reason is our body has a feedback loop that controls both hunger and satiety (sense of fullness) that makes it difficult for the person with overweight or obesity to obtain long-term weight loss.
When we start to lose weight, these signals will lead the body to increase hunger, decrease energy expenditure and reduce satiety. This is why most people can lose weight short-term with a restrictive diet, but these changes can’t be maintained long-term for continuous weight loss.
Here is a quick review of the three anti-obesity pharmacotherapies. Before prescribing or dispensing these products, it is important to review their product monographs.
Is 5-10% weight loss significant?
Although many people will like to lose large amounts of weight long-term, this is an unrealistic goal for many patients. A 5-10% weight reduction is usually a reasonable goal for patients.
Although it does not seem like a significant amount of weight loss, a review found that this amount of weight loss can lead to:
- A reduction in the risk of developing type 2 diabetes
- An improvement in blood pressure and dyslipidemia
- An improvement in A1C in people with diabetes
- An improvement in non-alcoholic fatty liver disease (NAFLD)
- A reduction in obstructive sleep apnea symptoms
- An improvement in osteoarthritis pain in weight bearing joints
- A reduction of GERD
- An improvement in polycystic ovary syndrome
What do I need to know about orlistat (Xenical)?
Orlistat is a lipase inhibitor in the GI tract. By inhibiting lipase, it prevents triglycerides being broken down to free fatty acids and monoglycerides that can be absorbed by the body. This translates to 30% reduction in the amount of fat being absorbed. With less fat, we have less calories, and thus weight loss.
The Xendos study evaluated the efficacy of orlistat over 4 years. It found that orlistat 120 mg 3/day was associated with a 5.8 kg weight reduction compared to 3.0 kg with placebo. It also reduced the risk of type 2 diabetes development (6.4% orlistat, 9.0% placebo). The biggest issue with this study was a high drop-out rate. Close to half of participants in both the orlistat and placebo groups dropped out.
GI related adverse effects are very common with orlistat. If a person eats too much fat, this will commonly lead to oily stools, diarrhea and abdominal discomfort.
Orlistat can impair the absorption of fat-soluble vitamins (A,D,E,K), so patients should be encouraged to take a multivitamin at bedtime. It is associated with drug interactions with cyclosporine, warfarin and anti-epilepsy medications.
The standard dose is 120 mg 3/day with each of the main meals. This is to prevent the fact absorption with the meal.
Bottom line: For some people orlistat is an option for weight reduction. Frequent dosing, adverse effects and lack of impact on the neurobiology of obesity translates to this option not being used as frequently as the other options.
What do I need to know about liraglutide 3.0 mg (Saxenda)?
The GLP-1 receptor agonist liraglutide has been used for the management of type 2 diabetes for many years. Liraglutide 3.0 mg (Saxenda) has been used for the last several years for the management of obesity. Liraglutide is very similar to endogenous GLP-1, but these small changes make it resistant to breakdown by the enzyme DPP-4.
Liraglutide acts on the hunger center in the hypothalamus of the brain and interacts the underlying neurobiology associated with obesity. GLP-1 has influence over the POMC pathway, which:
- Increases satiety (sense of fullness)
- Decreases appetite
- Decreases hunger
- Decreases energy intake
- Decreases gastric emptying
These changes are associated with weight reduction in people with obesity. The SCALE Obesity and Prediabetes trial assessed the efficacy of liraglutide 3.0 mg. Two-thirds of people on liraglutide 3.0 mg lost at least 5% of body weight (27% with placebo) and one-third lost at least 10% body weight (10.6% with placebo).
The most common adverse effects with liraglutide are GI effects such as nausea and vomiting. These are usually transient and can be mitigated with slowly titrating the dose. Gall bladder disease can occur with liraglutide, but is also common with weight reduction.
The dosing is 0.6 mg daily increasing by 0.6 mg each week until the dose of 3.0 mg daily is reached. The injection is given in the abdomen, thigh or upper arm.
Bottom line: Liraglutide 3.0 mg is an effective treatment for reducing a patient’s weight by 5-10%. This treatment targets the underlying neurobiology of obesity. Most adverse effects are mild and temporary. The subcutaneous injection may be a barrier for some patients.
What do I need to know about naltrexone/bupropion (Contrave)?
The newest anti-obesity agent in the Canadian market is Naltrexone/Bupropion (N/B). Like liraglutide, this medication targets a component of the underlying obesity neurobiology. It is thought that the bupropion has a dual mechanism of action. It increases the level of dopamine in the reward pathway but also stimulates the release of alpha-MSH and B-endorphins in the POMC pathway in the hypothalamus. Alpha-MSH promotes a decrease in food intake. Naltrexone is thought to block the effect of B-endorphin, which stimulates feeding. This combination of N/B is more effective than either agent alone.
The COR-1 trial found that approximately two-thirds of people who completed the trial (56 weeks) lost at least 5% of body weight (versus 23% with placebo) and 34% lost at least 10% body weight (versus 11% with placebo). Unfortunately, almost 40% of participants did not complete the trial.
The most common adverse effects are nausea, constipation, headache, vomiting, dizziness, insomnia and dry mouth. It is contraindicated in people with seizure disorders and chronic opioid users. Bupropion can interact with drugs metabolized by CYP 2D6 (metoprolol, SSRI’s, tricyclic antidepressants, risperidone, tamoxifen).
The dosing is started at 1 tablet daily for 1 week, then 1 tablet 2/day for 1 week, then 2 tablets in the morning and 1 tablet in the evening for a week, then 2 tablets 2/day.
Bottom Line: Naltrexone/bupropion is an effective agent that targets the underlying neurobiology of obesity. It will help some patients achieve the 5-10% weight reduction. The adverse effects and drug interactions can be a concern in some patients.
Image courtesy of the Obesity Canada Image Bank