Medications

Now that we are looking at weight loss with a new understanding of the way our metabolic thermostat regulates our fat stores, it seems entirely possible that medications that work on either your brain or your gut could adjust your body’s set point.  As you learned earlier, there are many medications that adjust your set point upward, so it makes sense to think that there must be some that adjust it downward.  Unfortunately, when we look closely at the weight loss medications that are currently available in the United States, we find that the “miracle drug” simply does not exist.  While it is entirely possible, and even probable, that this medication will be developed within the next 25 years, it has not been developed yet and there are no realistic miracle weight loss drugs in the pipeline at this time.  

Most physicians who prescribe weight loss medications reserve them for use only after nutritional changes and exercise have produced maximum weight loss for the patient.  There is wide variation in the response rate to weight loss medications.  While most (around 80%) do not achieve significant weight loss, there is a small subset (the remaining 20%) that can lose up to an additional 10% of their body weight. However, the effect is only maintained for as long as the patient is taking the medication.  Now that we understand the impact our metabolic thermostat has on hunger, metabolic rate, and the role of medications in lowering our body’s set point, this makes perfect sense.  However, many patients and even prescribing physicians, do not recognize the importance of the lifelong continuance of these drugs if the weight loss is to be maintained.

These limitations make medications a very small part of my therapeutic approach to treating patients for obesity without surgery.  However, I have found these drugs to be very useful if administered between 6 months to 2 years after surgery.  Often, medications can help patients who are struggling to succeed by enhancing the effect of the surgery.  I do not use them on every postoperative patient; only those whose weight loss is less than what we would expect.

The most commonly used weight loss medication is Phentermine, also known as Adipex.  Adipex has been in use since the early 70’s and can trigger significant weight loss in some people.  It is a stimulant drug in the amphetamine class that works both to decrease your appetite and increase your metabolic rate.  In essence, Adipex works to lower your set point.  Weight loss on Adipex is typically easy without requiring a significant change in your diet.  Adipex’s side effect profile prevents it from being taken indefinitely and needs to be cycled on and off.  The very predictable result of this dosing pattern is a cycle of yo-yo weight loss and gain.  Also, the effects of Adipex diminish over time so that patients who were initially successful with the drug, no longer see the same results the next time they start taking the medication.

Another commonly used medication is Topiramate; more commonly referred to as Topamax.  Topamax is primarily used as an anti-seizure drug. It has some mood stabilizing effects, as well, and may be useful in treating BiPolar disorder.  A pleasant side effect of Topamax is weight loss, however it is usually limited to 5-10 pounds.  It usually does not cause as much weight loss as Adipex and often does not induce any weight loss at all. But, it has a very favorable side effect profile and is inexpensive, making it a popular choice.  Often times, Adipex and Topamax are used in combination. In fact, a very smart pharmaceutical executive recognized that he could patent a “new weight loss drug” that consisted of both medications in one pill.  The result is Qsymia, which has been aggressively marketed by its manufacturer, but has not been widely adopted by physicians or patients.

Contrave is another example of the pharmaceutical industry using two older medications in combination as a “new drug.”  Contrave contains both Bupropion(Wellbutrin) and Naltrexone; a drug that works to block some of the pleasure signals in the brain.  These two drugs in combination offer modest weight loss for a subset of patients, but have very few side effects.  It is brilliantly named to indicate that it reduces your cravings for food, but there is no science to support reduced food cravings.  Contrave, like most other weight loss medications, does not work in most patients and must also be paired with good nutrition and exercise.  The average weight loss attributable to Contrave over one year is between 5-10 pounds which is merely the tip of the iceberg for most patients.

Belviq (Lorcaserin) is a new medication that is structurally similar to fenfluramine which was once part of the popular combination drug Fen-Phen (Phentermine and fenfluramine).  Fen-Phen was pulled from the market early this century and has resulted in legal damages to the manufacturer that exceeded $13 billion dollars as a result of the class action lawsuits that followed.  It appears that the manufacturers covered up fatal heart valve abnormalities attributed to the medication in early studies.  Belviq reports a much lower affinity for heart valves than was observed in fenfluramine, so there is reason to be optimistic that it won’t cause the same devastating complications that we saw with fenfluramine.  I have chosen not to prescribe it for a few years until it has been used widely enough to ensure that the risk is minimal.  Again, Belviq shows only modest weight loss in most patients, and in my opinion, does not warrant the very small, but still concerning risk of a heart valve abnormality.

The most recently approved weight loss medication (as of April 2015) is Saxenda (Liraglutide).  Liraglutide is also marketed under the trade name Victoza as an injectable diabetes drug in the GLP-1 analog class.  These medications have been very helpful in the treatment of diabetes and add an extra medication that can be used to help keep patients off insulin which has significant weight gaining effects, as we discussed earlier.  However, clever pharmaceutical executives have recognized that there is money to be made by re-branding these drugs as “new” weight loss medications, even though they have been available for over ten years.  Like all other drugs in the GLP-1 analog class, Saxenda causes slightly more weight loss than Qsymia, Contrave, or Belviq, but can only be given as an injection.  Unfortunately, Saxenda, like other GLP-1 analogs drugs often cause gastrointestinal discomfort; specifically nausea and diarrhea and has been linked to pancreatitis and thyroid cancer.

When we look closely at the weight loss medications currently available , it is easy to explain why less than 1% of the patients who qualify for the medication receive a prescription.  These medications are not new, despite the publicity. They are also expensive, can have significant side effects, and are only modestly effective in a subset of patients.  Somewhat jokingly, I often refer to inhaled tobacco smoke as the most effective weight loss agent currently available.  Many people think that people gain weight after quitting smoking because they change their fixation from smoking to eating.  However, a more likely explanation is that inhaled tobacco smoke is a powerful set point lowering agent.  When you quit smoking, you remove the set point lowering effect of the cigarettes and your metabolic thermostat triggers an increase in your appetite and a slowing of your metabolism which drives your body weight up to your new, higher set point.  This effect is largely unavoidable. Still, the dangers of smoking strongly outweigh the 10-20 extra pounds that usually result when you quit.  Additionally, as I will discuss later, smoking and bariatric surgery make a terrible mix and typically result in a miserable patient.  I believe that smoking cessation should be a critical component of any pre-operative bariatric surgery program.

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