Why Aren't We Prescribing Pills for Obesity?

Obesity is a complex, chronic metabolic disease purported to be caused by a combination of genetic predisposition and the environment. The prevalence of obesity in the United States is high, affecting more than one third of the population, according to national statistics.^[1]

Over the past 20 years, obesity medicine has developed as a subspecialty. Obesity specialists are dedicated to the treatment of obesity and its comorbidities, with a multidisciplinary team of professionals using a variety of tools that include diet, exercise, behavioral counseling, pharmacotherapy, and bariatric surgery.

Fewer than 2% of obese individuals in the United States are offered a prescription for weight-loss medications.

In the future, we may discover that obesity is, in reality, a group of related diseases or obesities, depending on the genetic composition that created the syndrome in a specific environment.

That said, in most cases, weight loss by diet, exercise, and behavioral change causes hormonal changes in the body that create physiologic revisions in energy balance, appetite, and satiety. These changes encourage regaining of weight to the original "body-weight set point." ^[2,3]The body-weight set point in obesity is altered upward because of the disease and a pathophysiology that creates a higher body-weight set point in this environment.

Obesity Drugs, Approved and Available

Medications for chronic obesity management have been approved by the US Food and Drug Administration (FDA) during the past few years and include five on-label single and combination agents: phentermine/topiramate, bupropion/naltrexone, orlistat, lorcaserin, and liraglutide 3.0 mg.

In 1- and 2-year randomized, placebo-controlled trials, use of these agents resulted in weight loss of approximately 5%-10% of original weight.^[3,4] They are approved for individuals with a body mass index (BMI) > 30 kg/m² or > 27 kg/m² with at least one serious comorbidity.^[3,4]

Phentermine alone is also approved for the treatment of obesity; however, it was approved in 1959 for 3 months of use only, although it is frequently used off-label for longer periods of time.^[4]

Why Aren't We Using Them?

Notwithstanding the efficacy of 5%-10% weight loss, fewer than 2% of obese individuals in the United States are offered and fill a prescription for one of these medications.^[5] Several reasons have been cited for this seeming reluctance on the part of physicians to prescribe medications that work and are safe.

One reason is insufficient insurance coverage of these prescriptions. Although coverage is improving, it is not 100% or even close to it at this point. Some of the newer medications are quite costly and, for many patients, financially untenable for chronic use.

If obesity is considered a moral failing, why treat it with a pill or surgery?

Another barrier is the public perception of obesity as a matter of will power rather than a disease. The general knowledge of obesity as a disease has not penetrated, and therefore many still see medications and bariatric surgery as the easy way out or a crutch. If obesity is considered a moral failing, why treat it with a pill or surgery?

Other barriers to the care of patients with obesity are lack of time on the part of the clinician and stigma, which clinicians link to lack of patient motivation.^[6]

Last, physicians are inadequately trained in obesity medicine. Efforts to train physicians have led to the formation of the American Board of Obesity Medicine and the advent of several obesity medicine fellowship programs around the country.

The USPSTF: Behavioral Approaches Only

The 2018 US Preventive Services Task Force (USPSTF) Recommendation Statement^[7] calls for clinicians to offer or refer patients with BMI > 30 kg/m² to intensive, multicomponent behavioral interventions as the safest way to treat obesity.

The statement does mention medications for the treatment of obesity and the trials that have shown their efficacy and safety. However, the conclusion to the section on pharmacotherapy states that the trials were fraught with limitations, including missing data and poor follow-up.

In addition, much is made of "multiple potential harms" of the medications, listing all side effects for each medication—from anxiety and dry mouth, which are more common, to pancreatitis, which is very rare. These are harsher critiques than those given to trials of antihypertensive agents or lipid-lowering agents, or even drugs for diabetes.

Chronic Therapy for a Chronic Condition

The discussion of pharmacotherapy interventions includes the statement that "data were lacking about the maintenance of improvement after discontinuation of pharmacotherapy." But you would not expect maintenance of improvement after discontinuing pharmacotherapy for hypertension or type 2 diabetes, which are considered diseases. Likewise, you should not expect sustained weight loss after discontinuing medication that readjusts the body-weight set point by improving satiety.^[7]

Weight loss can reduce morbidity from other chronic conditions that are exacerbated or caused by obesity.

Individuals with obesity need chronic therapy for this unrelenting disorder.^[8] Medications should be prescribed indefinitely, just as we prescribe antihypertensives indefinitely for hypertension.

These medications should be covered by third-party payers, because as long as they are taken, a significant 5%-10% weight loss will be achieved and maintained. The weight loss, in turn, can reduce morbidity from other chronic conditions that are exacerbated or caused by obesity.

Despite the benefits, only about 1% of eligible patients fill a prescription for a weight loss medication.^[5] Most often, this medication is phentermine, which is generic and inexpensive but FDA-approved for only 3 months of use.

Bariatric Surgery

Bariatric surgery offers a 25%-33% total weight loss with maintenance of most of that weight loss long-term,^[9] but less than 1% of eligible patients in the United States receive bariatric surgery.^[10] Mortality and complication rates are comparable to those of cholecystectomy.^[11]

Surgery is not mentioned at all in the USPSTF recommendations. However, bariatric surgery datasets have demonstrated efficacy and safety, with long-term follow-up with continued behavioral interventions offering the best maintenance of original weight loss over time. In addition, data show that offering pharmacotherapy for weight regain after bariatric surgery can mitigate the weight gain and salvage much of the surgery's initial success.^[12]

Obesity is a chronic relapsing disease that requires behavioral interventions and a multidisciplinary approach with intensification of treatment—including pharmacotherapy and surgery—depending on the BMI and comorbidities.

In the future, a stratified approach and algorithm will perhaps provide a better method to assess risk than the BMI, and combinations of available and newer therapies—including behavioral interventions, exercise therapy, pharmacotherapies, devices, and bariatric surgery—can be offered to achieve sustained and significant weight loss and amelioration of the risks for morbidity and mortality.

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