AACE 27th Annual Scientific & Clinical Congress:

Obesity-Focused Pharmacotherapy: Giving Your Patients What They Need

Borrowing from Lewis B. Carroll’s Alice in Wonderland view of the world for people with obesity, W. Timothy Garvey, MD, director of the Diabetes Research Center at the University of Alabama at Birmingham, confirmed what most clinicians are up against—patients’ desire for a pill that will just make them small.There is some value in this thinking. 

Dr. Garvey offered a clear case for establishing a consistent approach to prescribing pharmacotherapy as a way of facilitating successful weight management in patients with obesity,1 in a presentation at AACE 2018, the 27th Annual Scientific & Clinical Congress in Boston, Massachusetts. Dr. Garvey offered four overarching strategies to guide pharmacotherapy as an important aspect of managing obesity.

There is no one right or better medication for weight loss for everyone, rather this choice is based on specific patient needs.

The four "Ws," or general principles, to consider in initiating obesity pharmacotherapy are:1

  • Why use weight loss medications?
  • When should weight loss medications be prescribed?
  • What are the therapeutic targets of medication-assisted weight loss?
  • Which medications should be used?

However, to put these principles into context, Dr. Garvey argued in favor of changing the nomenclature away from “obesity” to better reflect the clinical nature of this disease, Dr. Garvey made a case for using: Adiposity-based chronic disease (ABCD) that goes beyond body mass index in considering therapeutic management of excessive adiposity.1,2

The purpose of reframing the medical diagnostic terminology has been developed to facilitate active engagement in the clinical management of this chronic disease, and to reflect the abnormalities impacted by mass, distribution, and function of adipose tissue in the pathophysiology of obesity and its comorbid diseases.2

Key points on each of the strategies were summarized by Scott Isaacs, MD, medical director at Atlanta Endocrine Associates in Atlanta, Georgia, who attended the session to report to EndocrineWeb.

Why prescribe weight loss medications?

Obesity is a chronic disease that involves interactions between genetic, environmental, and behavioral factors that result in cardiometabolic and biomechanical complications, which may prove responsive to medications similar to other chronic diseases such as diabetes, hypertension, or hyperlipidemia.1

The regulation of energy intake is mediated by peripheral signals from higher cortical centers, adipose cells, the gastrointestinal tract, and the pancreas that act on hypothalamic pathways and higher cortical centers. Obesity medications act along these pathways to decrease appetite and cravings as well as to increase satiety. The addition of a medication to the medical management of adiposity-based chronic disease has been demonstrated to produce greater weight loss and support better weight loss maintenance in comparison to lifestyle therapy alone.

When should weight loss medications be prescribed?

In accordance with a clinicians judgment and knowledge of the patient, treatment may be informed by the AACE clinical practice guidelines,3  which indicate that the use of pharmacotherapy should only be employed as an adjunct to and initiated concurrently with lifestyle therapy for obesity management in order to promote greater weight loss and improved weight-loss maintenance. Weight loss medications are prescribed for patients with a BMI > 30 kg/m2 or with a BMI > 27 kg/m2 when there is at least one ABCD-related comorbidity.

Patients deemed at elevated risk for obesity-related disease should be evaluated for clinical comorbidities and then assessed for the severity of any complications, including but not limited to hypertension, diabetes, or dyslipidemia (see Table 2).

What are the therapeutic targets of medication-assisted weight loss?

Therapeutic targets for weight loss are best determined by the stage of comorbid involvement with the express goal of reversing clinical complications to improve the patient’s outcomes.3

There are three scenarios to guide initiation of pharmacotherapy after lifestyle therapy has been trialed:

  • In patients who present with progressive weight gain or worsening of comorbid complications in which lifestyle therapy has been deemed insufficient.
  • To lessen or reverse tendency toward weight regain following initial weight loss success.
  • To promote greater weight loss in order to lessen weight-related complications.

Recommendations to guide when to prescribe antiobesity drugs.

 

Improvements in type 2 diabetes, hypertension, and dyslipidemia, for example, may be achieved in some patients with as little as 3 to 5% weight loss whereas other patients may require greater than a 15% loss of initial weight to reach desired therapeutic improvements in comorbid complications, and other conditions such as polycystic ovary syndrome, fatty liver disease, and sleep apnea, may require closer to a minimum of 10-15% weight loss to improve outcome(s).

Which medications should be used?

Currently, there are eight medications approved by the Food and Drug Administration (FDA) for use in supporting weight loss:

  • phentermine (Adipex-P®, Suprenza®)*
  • benzphetamine (Regimex®, Didrex®)*
  • orlistat (Xenical®, alli®)†
  • phentermine-topiramate ER (Qsymia®)†
  • liraglutide injection (Saxenda®)†
  • lorcaserin HCL (BELVIQ®)†
  • naltrexone HCl and bupropion HCl (CONTRAVE®)†
  • phendimetrazine (Bontril®)*
    *Approved for short-term use;  †Approved for long-term (chronic) use

In selecting the optimal weight loss medication for an individual patient, clinicians should consider differences in efficacy, side effects, cautions, warnings, and drug interactions along with the patient’s prior medical and weight loss history.

Location of metabolic action for medications approved to support weight loss and avoid weight regain.

Dr. Garvey indicated that all of these factors should be considered as the basis for formulating an efficacious, individualized approach to weight management as there is no single algorithm for medication selection or preferences.1 ,3

Targeted Weight Loss Rx for Specific Comorbidities1

Prediabetes—The recommended preferences for pharmacotherapy in patients with concurrent obesity and prediabetes is: phentermine/topiramate ER or liraglutide (3 mg) and secondarily: Orlistat or lorcaserin, which have been deemed moderately effective in achieving a reduction in diabetes risk of 36-45% and improvement in the patient’s lipid profile.

Obstructive sleep apnea—recommended first-line therapy is phentermine/topiramate ER, and second-line therapy to consider is liraglutide, which has been moderately effective.

Binge Eating or Nighttime Cravings—the best data point to naltrexone ER/bupropion ER and lorcaserin, however, naltrexone/bupropion are contraindicated in patients with bulimia (purging disorder).

 Concomitant psychiatric disorders—liraglutide or orlistat are the best pharmacotherapy options.

To best determine whether the current pharmacology regime is working for the patient, Dr. Garvey told EndocrineWeb that clinicians "key in on the health benefits that have been achieved as a result of weight loss."

Dr. Garvey’s financial disclosures include consulting fees and/or research support from Merck, Janssen, Novo Nordisk, Alexion, Pfizer, Sanofi, Eisai, Astra Zeneca, Lexicon, Weight Watchers, and Elcelyx. Dr. Isaacs has no conflicts to report.

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