New US Obesity Guidelines: Treat the Weight First

Miriam E Tucker

January 16, 2015

A new Endocrine Society clinical-practice guideline on the pharmacological management of obesity outlines a plan for the use of weight-loss agents as well as for shifting away from drugs to treat other conditions that promote weight gain.

The document represents "a blueprint for how to treat obesity with comorbidities," Dr Caroline M Apovian (Nutrition and Weight Management Center at Boston Medical Center, Massachusetts) said during a telephone press briefing to introduce the guidance.

Use of approved weight-loss medications is endorsed for people with a body mass index (BMI) of 30 kg/m2 and above or at least 27 kg/m2 with one or more comorbidities. The document "shifts the paradigm" by advising physicians to target the obesity itself first and thereby diminish its related complications — such as hyperglycemia, dyslipidemia, and hypertension — rather than aiming first to treat the comorbidities caused by the excess weight, she said.

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline, also endorsed by the Obesity Society (TOS) and the American Society for Metabolic and Bariatric Surgery, was published online January 15 in the Journal of Clinical Endocrinology and Metabolism.

Pharmacologic Focus

By focusing on drugs specifically, the new practice guideline is intended as a companion to the November 2013 Report on the Management of Overweight and Obesity in Adults from the US National Heart, Lung, and Blood Institute (NHLBI)issued via the American College of Cardiology (ACC), the American Heart Association (AHA), and TOS.

Dr Apovian, who also served on that writing panel, pointed out that the 2013 guidelines covered lifestyle, medications, and surgery but didn't go into detail about pharmacotherapy because there were few drugs available in the United States at the time it was written.

But in the past 4 months, the US Food and Drug Administration has approved bupropion/naltrexone (Contrave, Orexigen Therapeutics) and liraglutide (Saxenda, Novo Nordisk) for weight loss.

These agents join controlled-release phentermine and topiramate (Qsymia, Vivus), and lorcaserin (Belviq, Arena Pharmaceuticals), which were approved in the United States in 2012. Prior to that, orlistat was available as an over-the-counter medication (Alli, GlaxoSmithKline); it was initially approved as a prescription medicine (Xenical, Roche) in 1999. And stand-alone phentermine dates back even longer.

However not everyone is convinced of the safety of these new agents. Regulatory authorities in the European Union have been much slower to approve new obesity medications, only recently having given the green light to just one of these novel products, bupropion/naltrexone. The European authorities have previously rejected lorcaserin and phentermine/topiramate due to safety concerns.

A New Paradigm

Dr Apovian explained that a key emphasis of the new US guidance is the recognition that weight-loss drugs do not "work on their own," but rather should be used to amplify the effects of behavioral changes to reduce caloric consumption.

"The addition of these medications to the lifestyle program will result in greater weight loss overall and better maintenance of the weight loss."

And this is the first guidance "that specifically names the medications and the recommended doses and how to use them. There are patient selection criteria that go beyond the [body mass index] and actually talk about other comorbidities and which drugs we might suggest and which drugs to taper the patient off of," she noted.

The guidelines advise treating the weight first with lifestyle modification and medication and then managing the remaining comorbidities that have not responded to any weight loss, including hyperglycemia, hypertension, and dyslipidemia.

Typically, weight loss of just 3% will reduce blood glucose levels, while a 5% to 10% weight loss will begin to lower blood pressure, raise HDL cholesterol, and diminish sleep apnea, Dr Apovian noted.

The recommended approach to overweight/obese patients with type 2 diabetes, for example, is to start with metformin and if necessary to add a glucagonlike-peptide-1 (GLP-1) agonist followed by a sodium glucose transporter-2 (SGLT2) inhibitor rather than sulfonylureas or insulin, which can cause weight gain.

For patients already taking insulin, sulfonylureas, thiazolidinediones, beta-blockers, or certain specific selective serotonin-reuptake inhibitors (SSRIs) like paroxetine — all of which can lead to weight gain — the document provides advice on how to taper patients from those medications and switch them to alternative agents that don't increase weight.

Tailoring Treatment: Not an Easy Task

A table in the document lists the pros and cons of each of the agents, including cost, and some guidance is also provided about tailoring certain drugs to certain patients.

For example, orlistat and lorcaserin are less likely than other agents to raise blood pressure, a consideration for people with cardiovascular disease. And because topiramate is a teratogen, it should be avoided in pregnant women.

But for the most part, there isn't a lot of evidence for tailoring the medications, Dr. Apovian noted.

"In the end, you're going to give the best guess of which drug the patient should go on….If the patient doesn't lose 5% of their weight in 12 weeks, stop the drug and try another.

"Unless you can really get a clear idea of what you think the patient is going to do best on, you're going to be prescribing by trial and error....This is the question I get asked the most often. Unfortunately, the research isn't there to help us beyond that."

Cost Considerations: Weight-Loss Drugs Often Not Covered

The new document also endorses the AHA/ACC/TOS recommendations regarding the clinician role in the patient encounter, including screening for chronic conditions and secondary causes of obesity and formulating a treatment plan that includes at least monthly visits for the first 3 months, then at least every 3 months for the first year.

"Based on our literature review, the best weight-loss outcomes occur with frequent face-to-face visits," Dr. Apovian said, noting that insurers will typically cover them. "[Primary-care physicians] can bill for this."

And many payers now cover bariatric surgery, too, but unfortunately most don't cover the weight-loss drugs. Dr Apovian said she has recently heard from payers who say that even when they are covered, the drugs aren't used often enough.

"Certainly, insurance coverage will help tremendously, but if we don't have doctors out there who are trained to deliver the treatment in the manner we indicate in [both the 2013 and the current guidelines], we are not going to be able to utilize them even if they are covered by insurance….We're trying to get a cadre out there of doctors who can use these medications. Once that happens, insurers will start covering them. The disadvantage now is the price."

Dr Apovian serves on advisory boards for Amylin, Merck, Johnson & Johnson, Arena, Nutrisystem, Zafgen, Sanofi, Orexigen, and Enteromedics. She has received research funding from Lilly, Amylin, Aspire Bariatrics, GI Dynamics, Pfizer, Sanofi, Orexigen, MetaProteomics, and the Dr Robert C and Veronica Atkins Foundation. Disclosures for the coauthors are listed in the article.

J Clin Endocrinol Metab. Published online January 15, 2015.Article


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