Perspective

Societies target pharmacological treatment of obesity in new clinical practice guidelines

The Endocrine Society made recommendations on managing obesity through the use of prescription drugs in a new set of clinical practice guidelines published online in the Journal of Clinical Endocrinology & Metabolism.

“This is the first guideline that specifically names the medications, the recommended doses and how to use them,” Caroline M. Apovian, MD, FACN, FACP, of Boston University School of Medicine and Boston Medical Center, chair of the task force that wrote the guidelines, said in a virtual press conference. “There is patient selection criteria that goes beyond BMI to talk about other comorbidities, which drugs we might suggest and which drugs to taper the patient off.”

Caroline Apovian

Caroline M. Apovian

Slated to appear in the journal’s February 2015 print edition, “Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline” recommends when and how to use the range of weight loss therapies that have recently become available and addresses weight gain from medications for other conditions.

In the past 2 years, the FDA has approved four new therapies: lorcaserin (Belviq, Eisai) phentermine/topiramate (Qsymia, Vivus), naltrexone/bupropion (Contrave, Takeda) and liraglutide recombinant (Saxenda, Novo Nordisk). This adds to the fat-blocker orlistat, available as both prescription and over-the-counter treatments, for a total of six therapies.

“This guideline is targeted, focused and timely,” Donna H. Ryan, MD, of the Pennington Biomedical Research Center, Baton Rouge, Louisiana, a member of the guideline task force, told Endocrine Today. “We now have four brand new medications to use, and doctors need to know how to use them. This gives them some boundaries for use — some recommendations on when and how to prescribe, and the rationale.”

Donna Ryan

Donna H. Ryan

Guidance gap filled, paradigm shifted

The guideline, cosponsored by the European Society of Endocrinology and The Obesity Society (TOS), and also endorsed by the American Society of Bariatric and Metabolic Surgery, is the first of its kind.

“There were guidelines coming from several directions that were broad and general about obesity, but nothing on obesity medications,” Ryan said.

In 2014, the American Association of Clinical Endocrinologists and the American College of Endocrinology published its “Advanced Framework for a New Diagnosis of Obesity as a Chronic Disease” in Endocrine Practice. The “Guideline for the Management of Overweight and Obesity in Adults” backed by TOS, the American Heart Association and the American College of Cardiology, was published in Circulation in 2013.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) in 2006 offered guidance on the prevention of overweight and obesity in adults and children.

“Although anti-obesity drugs were mentioned, those guidelines did not go into detail because at the time, there were very few medications on the market and therefore very few randomized controlled trials with which to make recommendations,” Apovian said.

The guideline represents a profound shift in treatment paradigm — from addressing an array of unique comorbidities through medications, diet changes and bloodwork monitoring before obesity, to dealing with obesity first.

“Obesity causes most of the problems in the first place,” Apovian said. “The new treatment paradigm … is to manage the obesity first with lifestyle change and medications, and then manage the remainder of comorbidities that have not responded.”

PAGE BREAK

Adjunctive, monitored, not covered

The guideline underscores that all medications for chronic weight management should be used in conjunction with combination with diet and exercise for optimal benefit.

“What all the placebo-controlled randomized trials have taught us is that these medications will not work their best on their own,” Apovian said. “The medications amplify the effect of behavioral changes, diet and exercise and lifestyle change.”

Physicians treating patients for weight management should see them frequently, Apovian said. She noted the TOS guidelines call for monthly visits for the first 3 months, then at least every 3 months for the first year.

The new guidelines recommend a medication should be continued if a patient achieves ≥5% weight loss after 3 months, but discontinued and an alternate drug or approach considered if weight loss is not achieved or side effects occur over the same period.

“The best weight loss outcomes, based on our literature review, occur with frequent face-to-face visits — 16 visits per year on average,” Apovian said.

The coverage currently offered by the Centers for Medicare & Medicaid Services aligns with this frequency, and primary care physicians can bill for it, she noted.

Evidence shows that a combination of web-based programs and face-to-face visits can offer patients two-thirds of the total weight loss when face-to-face visits are not possible, Apovian said.

Patients can achieve an average 5 to 10% weight loss over one year and have a “good chance” of keeping the weight off with continued management over a few more, she said.

“Unfortunately, many, many of the insurance companies do not cover obesity treatments; Medicare and Medicaid do not,” Apovian said. But some payers who do cover medications to treat obesity have indicated they are not being used, she said.

Proper training of physicians to deliver the medications are needed, Apovian stressed. TOS, through its Obesity Medicine Certification Program, and efforts by the American Board of Obesity Medicine, are helping.

“We’re trying to get a cadre of doctors out there who can use these medications,” Apovian said. “Once that happens, insurance will start covering.”

Comorbidities, considerations, key recommendations

For patients with other disease states, the guidelines promote new approaches that could mean either a reduction in some medications or an addition of others to promote weight loss.

Managing weight initially will generally resolve the comorbidities that patients experience, Apovian said; this is especially true for triglycerides, HDL, blood pressure and impaired glucose tolerance.

“We found that as little as 3% weight loss can reduce blood sugar, and 5% to 10% can reduce hypertension, dyslipidemias and sleep apnea,” Apovian said.

Patients with diabetes and overweight or obesity should be treated with drugs that promote weight loss or have no effect on weight as first- and second-line treatments, according to the guidelines.

For patients with the trio of obesity, diabetes and high blood pressure, the guidelines recommend angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers — less likely than beta-adrenergic blockers to foster cause gain.

Physicians should not use phentermine or diethylproprion to treat patients with uncontrolled high blood pressure or history of heart disease, according to the guidelines.

With weigh gain a potential side effect of antidepressants, antipsychotic drugs and epilepsy medications, a shared decision-making process between physician and patient is recommended to evaluate all options.

Ryan credited endocrinologists with “stepping up and owning the obesity space” and underscored how recommendations from professional societies are needed to lead the way in advising providers on how to manage the disease.

“Physicians are not taught it in medical school, they are not taught it in their residencies and there is a huge need for authoritative information on what to do with patients,” Ryan said. “This document is aimed at all physicians and provides evidence-based recommendations for what they really need to do to help their patients.”

For more information:

Caroline M. Apovian, MD, FACN, FACP, can be reached at Boston Medical Center's Nutrition and Weight Management Center, Preston Family Building, 2nd Floor, 732 Harrison Ave., Boston, MA 02118; email: caroline.apovian@bmc.org.

Donna H. Ryan, MD, can be reached at Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808; email: Donna.Ryan@pbrc.edu.

Apovian CM. J Clin Endocrinol Metab. 2015;doi: 10.1210/jc.2014-3415

Garvey WT. Endocr Pract. 2014;doi:10.4158/EP14280.PS.

Jensen MD. Circulation. 2013;doi:10.1161/01.cir.0000437739.71477.ee.

Disclosure: Apovian reports significant financial interests or leadership positions with Zafgen Inc, MYOS Corporation, Eisai, Vivus, Orexigen Theraputics and Takeda, and serving as NIH grantee or reviewer. Ryan reports financial or business/organizational interests with TOS and significant financial interests or leadership positions with Vivus, Eisai, Eisai Inc, Jansenn, Novo Nordisk, Takeda and Scientific Intake.

The Endocrine Society made recommendations on managing obesity through the use of prescription drugs in a new set of clinical practice guidelines published online in the Journal of Clinical Endocrinology & Metabolism.

“This is the first guideline that specifically names the medications, the recommended doses and how to use them,” Caroline M. Apovian, MD, FACN, FACP, of Boston University School of Medicine and Boston Medical Center, chair of the task force that wrote the guidelines, said in a virtual press conference. “There is patient selection criteria that goes beyond BMI to talk about other comorbidities, which drugs we might suggest and which drugs to taper the patient off.”

Caroline Apovian

Caroline M. Apovian

Slated to appear in the journal’s February 2015 print edition, “Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline” recommends when and how to use the range of weight loss therapies that have recently become available and addresses weight gain from medications for other conditions.

In the past 2 years, the FDA has approved four new therapies: lorcaserin (Belviq, Eisai) phentermine/topiramate (Qsymia, Vivus), naltrexone/bupropion (Contrave, Takeda) and liraglutide recombinant (Saxenda, Novo Nordisk). This adds to the fat-blocker orlistat, available as both prescription and over-the-counter treatments, for a total of six therapies.

“This guideline is targeted, focused and timely,” Donna H. Ryan, MD, of the Pennington Biomedical Research Center, Baton Rouge, Louisiana, a member of the guideline task force, told Endocrine Today. “We now have four brand new medications to use, and doctors need to know how to use them. This gives them some boundaries for use — some recommendations on when and how to prescribe, and the rationale.”

Donna Ryan

Donna H. Ryan

Guidance gap filled, paradigm shifted

The guideline, cosponsored by the European Society of Endocrinology and The Obesity Society (TOS), and also endorsed by the American Society of Bariatric and Metabolic Surgery, is the first of its kind.

“There were guidelines coming from several directions that were broad and general about obesity, but nothing on obesity medications,” Ryan said.

In 2014, the American Association of Clinical Endocrinologists and the American College of Endocrinology published its “Advanced Framework for a New Diagnosis of Obesity as a Chronic Disease” in Endocrine Practice. The “Guideline for the Management of Overweight and Obesity in Adults” backed by TOS, the American Heart Association and the American College of Cardiology, was published in Circulation in 2013.

In the United Kingdom, the National Institute for Health and Care Excellence (NICE) in 2006 offered guidance on the prevention of overweight and obesity in adults and children.

“Although anti-obesity drugs were mentioned, those guidelines did not go into detail because at the time, there were very few medications on the market and therefore very few randomized controlled trials with which to make recommendations,” Apovian said.

The guideline represents a profound shift in treatment paradigm — from addressing an array of unique comorbidities through medications, diet changes and bloodwork monitoring before obesity, to dealing with obesity first.

“Obesity causes most of the problems in the first place,” Apovian said. “The new treatment paradigm … is to manage the obesity first with lifestyle change and medications, and then manage the remainder of comorbidities that have not responded.”

PAGE BREAK

Adjunctive, monitored, not covered

The guideline underscores that all medications for chronic weight management should be used in conjunction with combination with diet and exercise for optimal benefit.

“What all the placebo-controlled randomized trials have taught us is that these medications will not work their best on their own,” Apovian said. “The medications amplify the effect of behavioral changes, diet and exercise and lifestyle change.”

Physicians treating patients for weight management should see them frequently, Apovian said. She noted the TOS guidelines call for monthly visits for the first 3 months, then at least every 3 months for the first year.

The new guidelines recommend a medication should be continued if a patient achieves ≥5% weight loss after 3 months, but discontinued and an alternate drug or approach considered if weight loss is not achieved or side effects occur over the same period.

“The best weight loss outcomes, based on our literature review, occur with frequent face-to-face visits — 16 visits per year on average,” Apovian said.

The coverage currently offered by the Centers for Medicare & Medicaid Services aligns with this frequency, and primary care physicians can bill for it, she noted.

Evidence shows that a combination of web-based programs and face-to-face visits can offer patients two-thirds of the total weight loss when face-to-face visits are not possible, Apovian said.

Patients can achieve an average 5 to 10% weight loss over one year and have a “good chance” of keeping the weight off with continued management over a few more, she said.

“Unfortunately, many, many of the insurance companies do not cover obesity treatments; Medicare and Medicaid do not,” Apovian said. But some payers who do cover medications to treat obesity have indicated they are not being used, she said.

Proper training of physicians to deliver the medications are needed, Apovian stressed. TOS, through its Obesity Medicine Certification Program, and efforts by the American Board of Obesity Medicine, are helping.

“We’re trying to get a cadre of doctors out there who can use these medications,” Apovian said. “Once that happens, insurance will start covering.”

Comorbidities, considerations, key recommendations

For patients with other disease states, the guidelines promote new approaches that could mean either a reduction in some medications or an addition of others to promote weight loss.

Managing weight initially will generally resolve the comorbidities that patients experience, Apovian said; this is especially true for triglycerides, HDL, blood pressure and impaired glucose tolerance.

“We found that as little as 3% weight loss can reduce blood sugar, and 5% to 10% can reduce hypertension, dyslipidemias and sleep apnea,” Apovian said.

Patients with diabetes and overweight or obesity should be treated with drugs that promote weight loss or have no effect on weight as first- and second-line treatments, according to the guidelines.

For patients with the trio of obesity, diabetes and high blood pressure, the guidelines recommend angiotensin converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers — less likely than beta-adrenergic blockers to foster cause gain.

Physicians should not use phentermine or diethylproprion to treat patients with uncontrolled high blood pressure or history of heart disease, according to the guidelines.

With weigh gain a potential side effect of antidepressants, antipsychotic drugs and epilepsy medications, a shared decision-making process between physician and patient is recommended to evaluate all options.

Ryan credited endocrinologists with “stepping up and owning the obesity space” and underscored how recommendations from professional societies are needed to lead the way in advising providers on how to manage the disease.

“Physicians are not taught it in medical school, they are not taught it in their residencies and there is a huge need for authoritative information on what to do with patients,” Ryan said. “This document is aimed at all physicians and provides evidence-based recommendations for what they really need to do to help their patients.”

For more information:

Caroline M. Apovian, MD, FACN, FACP, can be reached at Boston Medical Center's Nutrition and Weight Management Center, Preston Family Building, 2nd Floor, 732 Harrison Ave., Boston, MA 02118; email: caroline.apovian@bmc.org.

Donna H. Ryan, MD, can be reached at Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808; email: Donna.Ryan@pbrc.edu.

Apovian CM. J Clin Endocrinol Metab. 2015;doi: 10.1210/jc.2014-3415

Garvey WT. Endocr Pract. 2014;doi:10.4158/EP14280.PS.

Jensen MD. Circulation. 2013;doi:10.1161/01.cir.0000437739.71477.ee.

Disclosure: Apovian reports significant financial interests or leadership positions with Zafgen Inc, MYOS Corporation, Eisai, Vivus, Orexigen Theraputics and Takeda, and serving as NIH grantee or reviewer. Ryan reports financial or business/organizational interests with TOS and significant financial interests or leadership positions with Vivus, Eisai, Eisai Inc, Jansenn, Novo Nordisk, Takeda and Scientific Intake.

    Perspective
    W. Timothy Garvey

    W. Timothy Garvey

    The recent Endocrine Society guidelines for the pharmacologic management of obesity will help promote high quality care for the patient with obesity. These authors have reviewed the data pertaining to the pharmacotherapy of obesity, and their evidence-based analyses generally confirm and support FDA prescribing information for the various weight loss medications.

    However, these authors have also provided expert opinion that is also well-supported, and I believe this component of the report is a valuable and welcome addition in the field of obesity medicine.

    First, the authors have clearly delineated relative advantages and disadvantages of the various agents in different clinical scenarios reflecting FDA cautions and warnings as well as published side effect profiles of weight loss medications.

    Second, forthright recommendations are provided against the use of drugs that produce weight gain in favor of that weight-losing or weight-neutral alternatives for various diseases. This aspect of obesity management has been underemphasized, and the authors give this great emphasis for more optimal care of patients.

    Third, there is a clear recommendation against the off-label use of medications for weight loss.

    Finally, the recommendations stress the use of the medications to promote long-term maintenance of weight loss particularly in patients with hypertension, dyslipidemia, type 2 diabetes and obstructive sleep apnea. In this regard, the guidelines are moving closer to the complication-centric guidelines proposed by the American Association of Clinical Endocrinologists (AACE), which target more intensive treatment regimens to those patients with weight-related complications in an effort to optimize outcomes, safety, benefit/risk ratios and cost-effectiveness of obesity care. Along these lines, as also delineated in the AACE algorithm, there is the recommendation that clinicians consider weight loss therapy as a primary approach in type 2 diabetes to achieve improvements in glycemic control and cardiovascular risk factors.

    In summary, the Endocrine Society guidelines will help advance the practice of obesity medicine, and clinicians should become conversant with these recommendations. The guidelines and recommendations will promote rational approaches in obesity patient management and better outcomes in patient care.

    • W. Timothy Garvey, MD
    • Professor and Chair, Department of Nutrition Sciences, University of Alabama at Birmingham Director, UAB Diabetes Research Center Chair, AACE Obesity Scientific Committee

    Disclosures: Garvey reports that he has received advisory board honoraria and research support from various pharmaceutical companies.