Charles P. Vega, MD: Hello. Welcome to Critical Issues in Obesity. I am Chuck Vega, clinical professor of family medicine at the University of California in Irvine. Today I am delighted to be joined by Dr Caroline Apovian, professor of medicine and pediatrics at Boston University School of Medicine. She is also the director of nutrition and weight management at Boston Medical Center. Caroline, great to have you. Thanks for coming.
Caroline M. Apovian, MD: Nice to be here, Chuck. Thank you.
Dr Vega: I certainly don't need to tell you or any of the clinicians out there about the problem of obesity in the United States. According to data[1] from the Centers for Disease Control and Prevention (CDC), more than one third of US adults continue to be obese. Rates of obesity are particularly high among racial and ethnic minorities. For example, nearly one half of non-Hispanic black adults are obese, as well as 42% of Hispanic adults. Although the prevalence of obesity among adults was fairly steady over a decade, it did increase by 3% between 2011 and 2014.
We also know that for many people, the problem of obesity does not start in adulthood. It begins during childhood and adolescence. Overall, approximately 17% of US children and adolescents are obese, again with a higher rate of obesity among non-Hispanic black and Hispanic children.[1] Here, the prevalence of obesity has remained fairly steady throughout the decade.
My first choice, and what most people recommend to patients when it comes to obesity management, is a lifestyle change focusing on diet and exercise. In clinical trials, the results are usually about 1-10 kg of weight loss.[2] In my clinical practice, I feel like we've had a great success if we can achieve a 5-kg weight loss, depending on the patient.
At the same time, there are some new antiobesity drugs. In fact, four have been introduced during the past several years, yet these drugs are tremendously underutilized. A recent study[3] looked at uptake of the four new antiobesity drugs: phentermine/topiramate, liraglutide, naltrexone/bupropion, and lorcaserin. The investigators examined the rates of prescriptions for these drugs on a monthly basis vs another new class of drugs, the sodium/glucose cotransporter-2 (SGLT2) inhibitors, for diabetes. They found that the rate of SGLT2 inhibitor prescriptions was about five times that of all four drugs for obesity combined. Yet, obesity is a lot more common.
These drugs have a track record now. They have been researched. Yet, they are not being used widely.
Caroline, my first question to you is, what do you think about that situation? What is standing in the way of increased use of these medications in the management of obesity?
Dr Apovian: That is a very good question, Chuck. First of all, the primary issue is that obesity is not considered to be a disease by most people, clinicians included. For the most part, people still think that obesity is a matter of willpower—that it's just a matter of eating less and exercising more. Even though the American Medical Association (AMA) proclaimed obesity to be a disease in 2013,[4] there are still some things that need to be done for us to truly embrace obesity as a disease.
Even though we have these four newer medications, we actually have others. We have a total of six medications, two of which have been previously approved. In general, they are not covered by third-party payers' insurance. The first step in accepting obesity as a disease is to have coverage for the treatment, right?
Dr Vega: Right, of course.
Dr Apovian: Diet and exercise treatment is now covered by the Centers for Medicare & Medicaid Services (CMS). Doctors are reimbursed pretty poorly for treatment of obesity with lifestyle. Most doctors see a patient every 10 minutes. It's more cost-effective for the doctor to treat hypertension and diabetes instead of obesity, because it takes a while to talk about lifestyle change. Quite frankly, we don't look at lifestyle for a patient with elevated lipids. Who does that? Who treats a patient with elevated lipids with lifestyle alone?
Dr Vega: It's very rare.
Dr Apovian: Why do we treat obesity with lifestyle alone if obesity is a disease?
Treating Obesity: Where to Start
Dr Vega: That is a great point. For the clinician who is not as experienced, you mentioned some of the older drugs. Phentermine and orlistat should not be discounted just because they were approved previously.
What is your approach to pharmacotherapy if you have a patient with obesity who is free of comorbidities at this point? The patient is fairly young, 35 years old, but has a body mass index (BMI) of 35 kg/m2 and wants to lose weight. The patient has tried several good diet plans and has tried exercise. Metabolically, there are no red flags. Where do you go?
Dr Apovian: You talk about all the treatment options. In terms of lifestyle, we have treatment options. We have a medical fast called the protein-sparing modified fast. We have liquid diets, high protein diets, the Mediterranean diet, low-fat diets. We teach patients about the macronutrient content of their diet and how to change it to a healthier plan. After talking about those permutations of dietary choices, we also talk about getting extra physical activity on most days of the week.
That approach is different from every other disease process that can be treated by lifestyle as well—such as diabetes, hypertension, and hyperlipidemia. Because for many clinicians, that is all they offer.
However, we can also prescribe some medications that can suppress appetite. With medications, most of them will help a patient lose 5%-10% of their body weight. That is considered successful weight loss, because you see cardiovascular and anatomical benefits at this level of weight loss in most people.
When we get the 5%-10% weight loss, the first question I am asked is, "Should I stop the drug?" Even doctors will say to stop the drug. The only reason this is asked is because these drugs are expensive. And many don't realize that obesity should be treated chronically. It is a chronic disease. No one would ask when a patient should stop their hypertensive agent or insulin for their diabetes. You know the diabetes or hypertension will come back. Patients usually regain the weight when an appetite suppressant drug is stopped.
Dr Vega: I definitely have some patients asking me that on a regular basis.
Dr Apovian: Yes—"When can I stop this drug? It's too expensive, and I think I can keep the weight off now."
Dr Vega: You're absolutely right. I see the difference. I see the distinction.
Dr Apovian: The paradigm has to shift. It has not shifted yet. It would certainly help if we got insurance coverage for the medications that patients need for a 10% weight loss. Then we won't have patients going to the pharmacy and, seeing that the drug is going to cost $200/ per month, decide that they can't afford it because they have other drugs that they need.
Dr Vega: That is very defeating.
Dr Apovian: If you get a 10% weight loss, you can get the patient off other drugs for comorbidities. The number-one treatment you can get rid of immediately after a 10-lb weight loss, not 10%, is antireflux medications. Wipe those out. A 10% weight loss will reduce or eliminate drugs for diabetes, hypertension, lipids, and sleep apnea. With a 20% weight loss, the need for continuous positive airway pressure (CPAP) for sleep apnea may be eliminated because hypopnea episodes will decrease at nighttime. Incremental weight loss will incrementally decrease risk for other comorbidities. That has to be added into the cost/benefit analysis of treating obesity.
Are We Failing Our Patients?
Dr Vega: Let me ask a couple of follow-up questions. First of all, for diet counseling, I agree that a menu of different diet options is great. You have your highly motivated patients and your less motivated patients. There are a lot of cultural issues with food, both personally and within communities. Are you doing all that counseling yourself, or do you have a team around you that assists with that? That is a lot of work.
Dr Apovian: I used to do that all by myself when I was in primary care. Now I direct a subspecialty practice, and we have a team of five doctors, five dietitians, and three nurse practitioners. Just like cardiovascular disease, we need a team approach.
Also on our team are the bariatric surgeons, because bariatric surgery should be the treatment of choice for patients with BMI over 40 kg/m2 or over 35 kg/m2 in patients with a comorbidity that is very serious if they have failed diet, exercise, and a medication.
Having said this, medications for obesity are used less than 2% of the time. In other words, less than 2% of patients in the United States who are eligible for an antiobesity medication get it. Less than 1% of the time, patients who are eligible for bariatric surgery actually get it. If I told you that that was true for heart disease, you would tell me that we are negligent. This is the case in 2016 in the United States. We have to do something about this.
When to Change the Drug
Dr Vega: Let me ask one more clarifying question. You discuss the drugs available and start your patient on the drug. If they get a good result and feel good about taking them without having side effects, will they be continued indefinitely? Do you think about breaking off at 1 year, 2 years, 5 years, or not at all? Does it depend on the patient?
Dr Apovian: You bring up a few good points. The labels on most of the drugs say that if you do not get a response in 12 weeks, change the drug. "Response" means a 5-lb weight loss. You need to see weight loss because these drugs do not work the same way in everybody. That is why we have several drugs. They have different mechanisms. Most of them work in the brain. However, some people don't respond. You don't want to give a drug to a patient if they are not losing weight, because you are going to get the side effects and not the benefits of the drug for weight loss.
Good weight loss is 5 lb in 12 weeks, which translates to a 5%-10% weight loss in 6 months. In order to keep that weight off, the patient has to stay on the drug. That is part of the definition of a disease. It's the same with blood pressure. If somebody's blood pressure is controlled with lisinopril and you stop the drug, their blood pressure is going to go back up.
The same is true with obesity. It's a disease of the energy regulation system in the hypothalamus. There is a problem in the pathways that go from your gut and your adipose tissue to your brain. Most people in this environment are defending a higher body set point. That is the hypothesis that needs to be fully proven. For the most part, research shows that obesity is a disease, and that it is caused by a dysfunction of these pathways. Some of these medications restore the functionality of the appetite/satiety regulation system in the hypothalamus to keep off a 5%-10% weight loss. They restore it for as long as the patient takes the drug.
Safety of Antiobesity Medications
Dr Vega: That makes sense. Let me ask you one more question: Are there any important safety signals that have emerged with the older or newer agents that you are concerned about?
Dr Apovian: There are side effects for most drugs on the market.
Dr Vega: I'm not talking so much about tolerability, but something that would be a specific warning or contraindication. For example, with fen/phen (fenfluramine/phentermine) and the concern for heart pathologies, many clinicians who had been prescribing that drug felt burdened. Therefore, I think there is hypervigilance around the safety of weight-loss therapy in particular. Maybe it's not necessarily warranted. These new drugs have been fairly scrutinized, and they are not that new. They've been out now for several years.
Dr Apovian: I think that we are way beyond our understanding of drug mechanisms of action since fen/phen. Phentermine is still on the market. It has no increased risk for valvulopathy. It was the fenfluramine that was the problem—the excessive release of serotonin into the bloodstream causing valvulopathy.
We are in the infancy stage with obesity treatment. We have many different medications for hypertension on the market. Initially, the first drugs for hypertension had untoward side effects. We are now understanding more and more about obesity. These four new drugs are approved by the US Food and Drug Administration. They have 2-year data behind them, just like the data that are needed for the FDA to approve diabetes drugs and hypertension drugs. We also have 5-year cardiovascular outcomes trials that are currently being done to make sure that these drugs don't increase the signal for cardiovascular incidents—which has been true of some of the diabetes drugs, some of which have been indeed taken off the market.
We have to balance the risks vs benefit of these drugs, just like we balance the risks vs benefit of giving a patient a drug for diabetes. Incidentally, insulin and sulfonylurea can make diabetes worse in the end because they cause weight gain and exacerbate insulin resistance.[5]
The paradigm needs to shift. We need to fully embrace obesity as the disease that it is so we can get treatment to patients. For example, the benefit from lorcaserin is almost a 5% weight loss, with very little risk. It is a serotonin-like agent, but numerous studies have never shown any signal for valvulopathy.[6,7]
Phentermine/topiramate is a combination of two drugs that have been on the market for years: topiramate and phentermine. Topiramate use in pregnant women can cause an increased risk for cleft palate in the fetus,[8] so you have to be careful to counsel young women on this drug about the need for appropriate contraception. Topiramate is an antiseizure agent. It is also a drug used for migraine headaches.
Bupropion/naltrexone should not be used in someone who is on an opiate, obviously. In addition, bupropion can cause an increase in blood pressure and seizures,[9] but we don't think twice when we give bupropion for depression or smoking cessation. Again, obesity is an epidemic in this country. Many Americans have obesity, whereas fewer Americans have seizure disorder, and so the drug is looked at with increased scrutiny when used as an obesity agent. The blood pressure issues have caused the FDA to think about whether or not to approve this combination and on initial submission was not approved It was of course later approved
Liraglutide is a glucagon-like peptide-1 (GLP1) agonist, a naturally occurring hormone. The only common side effect that we worry about is nausea.
Dr Vega: Tolerability is an issue there, but in terms of safety, liraglutide is okay.
Dr Apovian: Four relatively safe drugs.
Dr Vega: Yes, I think so, too, although I understand where the ongoing cardiovascular surveillance and scrutiny comes from. So far, we are clear, and it seems like we should be thinking about obesity in a different way and including these medications as an option for patients, which does not seem to be happening very broadly right now. We will see how that evolves.
Dr Apovian: We need more than 2% of the eligible population being prescribed these drugs. That involves not only coverage—coverage by third-party payers as well as CMS—but also doctors who are educated on how to treat obesity. As far as I'm concerned, physicians are still not educated enough in medical school and during internships and residencies.
We need more obesity medicine fellowships. We have very few in the country. We have an obesity medicine certification program that is now certifying 500 doctors/year. It is only in its infancy—just 3 or 4 years old now. This is starting to happen. We need to educate doctors as well as patients and the population that obesity is a disease.
Dr Vega: Right. The epidemiology, comorbidities, social stigma, and everything else are all on your side. I would love to get more in the weeds with you regarding the mechanisms of these drugs and their efficacy data, but Medscape has another activity that explores those issues.
I hope this discussion gets everybody fired up about the management of obesity. I can tell that you are. I appreciate that passion; it's outstanding. I appreciate your time and your candor. We look forward to seeing you next time on Critical Issues. Thank you again, Caroline.
Dr Apovian: Thank you for having me, Chuck.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Obesity Is a Disease That Needs to Be Taken Seriously - Medscape - Jan 19, 2017.
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