New Obesity Guidelines Recommend Nuanced Treatment

More than one third of adults in the United States today are classified as obese. Defined as a body mass index (BMI) of ≥30 kg/m², obesity is associated with extremely high medical costs, including absenteeism. In addition, comorbidities related to obesity are many of the leading causes of preventable death: heart disease, stroke, type 2 diabetes, and certain types of cancer.⁴

Significant and clinically relevant improvements in cardiovascular disease risk factors such as glycemia, blood pressure, triglycerides, and HDL cholesterol can be produced with modest weight loss, 5% to 10% of body weight, with even greater improvements observed with reductions of 10% to 15% of body weight.⁴

As a heterogenous disease, obesity requires an individualized approach to treatment. The new evidence-based American Association of Clinical Endocrinologists/American College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity provides a comprehensive treatment algorithm that includes whether the patient presents with “weight-related disease or complication that could be improved by weight loss therapy.”¹

The guidelines differentiate between an “anthropometric component” of the medical diagnosis of obesity, defined as excess adiposity, and the “clinical component,” defined as weight-related complications. These 16 complications are prediabetes, metabolic syndrome, type 2 diabetes, dyslipidemia, hypertension, cardiovascular disease, nonalcoholic fatty liver disease, polycystic ovary syndrome, female infertility, male hypogonadism, obstructive sleep apnea, asthma/reactive airway disease, osteoarthritis, urinary stress incontinence, gastroesophageal reflux disease, and depression.

Based on clinical judgment, for patients who are obese with at least 1 severe complication, suggested treatment may include lifestyle therapy (meal plan, physical activity, and behavioral intervention), the addition of pharmacotherapy (BMI ≥27 kg/m²), or consideration for bariatric surgery (BMI ≥35 kg/m²).^{1, 3}

The AACE/ACE guidelines recommend that weight loss medications be initiated as an adjunct to lifestyle therapy when a patient has failed or regained weight on lifestyle therapy or in the presence of weight-related complications. The algorithm categorizes the five US Food and Drug Administration-approved weight-loss medications for chronic weight management as “preferred drug,” “use with caution,” or “avoid” to help clinicians individualize treatment based on a patient’s clinical characteristics or coexisting disease. A total of 19 are included, from diabetes prevention to hepatic impairment to opioid use to post-bariatric surgery.¹ 

These five weight-loss medications—orlistat, lorcaserin, phentermine/topiramate ER, naltrexone/bupropion, and liraglutide—and where they rank as “preferred agents” based on comorbidity or patient characteristics are highlighted in the Table. The FDA indication for all medications is BMI ≥30 kg/m² or BMI ≥27 kg/m² with significant comorbidity.¹

The American Heart Association/American College of Cardiology, The Obesity Society and The Endocrine Society guidelines also endorse consideration of antiobesity medications.⁴ However, a recent study found few received this option: of more than 2 million eligible patients, only 1% were written a prescription, and their use of these medications was not continuous.² Cited barriers to successful use of weight-loss medications include lack of physician training, lack of reimbursement for office visits, and poor insurance coverage.⁴

These are all areas that need improvement in order to better treat obesity as a chronic disease.

Anti-obesity agents in the pipeline are the injectable beloranib, which reduces appetite and stimulates use of stored fat; low-dose phentermine; and combination therapies.

Sources

1.       American Association of Clinical Endocrinologists/American College of Endocrinology. AACE/ACE Algorithm for the Medical Care of Patients with Obesity. Available at: https://www.aace.com/files/guidelines/ObesityAlgorithm.pdf

2.   Bessesen DH, McCormick E, Saxon, DR, et al. Patterns of prescribing weight loss medications in a large cohort of adults. Paper Presentation at ENDO 2016, Boston, MA, April 3, 2016. Available at: https://endo.confex.com/endo/2016endo/webprogram/Paper28282.html

3.   Garvey WT, Mechanick JI, Brett EM, et al., and Reviewers of the AACE/ACE Obesity Clinical Practice Guidelines. American Association of Clinical Endocrinologists and American College of Endocrinology. Clinical Practice Guidelines for Comprehensive Medical care of Patients with Obesity – Executive Summary. Endocr Pract. 2016; DOI:10.4158/EP161365.GL. Available at: https://www.aace.com/files/guidelines/ObesityExecutiveSummary.pdf

4.   Saunders KH, Kumar RB, Igel LI, Aronne LJ. Pharmacologic approaches to weight management: recent gains and shortfalls in combating obesity. Curr Atheroscler Rep. 2016;18:36.

U.S. Food and Drug Administration-Approved Agents for Long-term Treatment of Obesity

Agent

Trade Name

FDA Approval

MOA

Preferred Agent for the Following Coexisting Disease/Patient Characteristic

Possible Adverse Events

Orlistat (capsule)

Xenical Alli (OTC)

1999

Lipase inhibitor

Age ≥65 years (limited data) Alcoholism/addiction Anxiety Binge eating disorder Cardiovascular disease (CAD, arrhythmia) Chronic kidney disease (mild or moderate) Depression Diabetes prevention (metabolic syndrome, prediabetes) Glaucoma Hypertension Opioid Use Pancreatitis (monitor for symptoms) Seizure disorder Type 2 diabetes Women of reproductive potential (discontinue with pregnancy)

Oily spotting Flatus with discharge Fecal urgency Fatty/oily stool Oily evacuation Increased defecation Fecal incontinence

Lorcaserin (tablet)

Belviq

2012

Serotonin (5HT2c) receptor antagonist; promotes appetite suppression, increases satiety

Anxiety Cardiovascular disease (CAD, arrhythmia [monitor for bradycardia]) Chronic kidney disease (mild or moderate) Glaucoma Hypertension Nephrolithiasis Opioid Use Pancreatitis Seizure disorder Type 2 diabetes Women of reproductive potential (discontinue with pregnancy)

Non-diabetic patients: Headache Dizziness Fatigue Nausea Dry mouth Constipation Diabetic patients: Hypoglycemia Headache Back pain Cough Fatigue

Phentermine/ topiramate ER (capsule)

Qsymia

2012

Phentermine: NE-releasing agent; promotes weight loss via sympathetic nervous system activation Topiramate: GABA receptor modulation; suppresses appetite, enhances satiety

Age ≥65 years (limited data) Anxiety (avoid maximum dose) Chronic kidney disease (mild or moderate; for moderate, do not exceed recommended dose) Depression (avoid maximum dose) Diabetes prevention (metabolic syndrome, prediabetes) Hypertension (monitor heart rate) Opioid use Pancreatitis Post-bariatric surgery (limited data) Seizure disorder (if discontinued at maximum dose, taper slowly) Type 2 diabetes mellitus Women of reproductive potential (discontinue with pregnancy; check monthly to identify early)

Paresthesia Dizziness Dysgeusia Insomnia Constipation Dry mouth

Naltrexone/bupropion (extended-release tablets)

Contrave

2014

Naltrexone: Opioid antagonist Bupropion: Reuptake inhibitors of DA and NE Synergistic action in the CNS reward pathways reduces food intake

Anxiety Chronic kidney disease (mild or moderate; for moderate, do not exceed Week 2 dose) Nephrolithiasis Pancreatitis Type 2 diabetes mellitus Women of reproductive potential (discontinue with pregnancy)

Nausea Constipation Headache Vomiting Dizziness Insomnia Dry mouth Diarrhea

Liraglutide (SC injection)

Saxenda

2014

Glucagon-like peptide-1 (GLP-1) receptor agonist; improves glycemic control, decreases appetite, enhances satiety

Age ≥65 years (limited data) Alcoholism/addiction Anxiety Chronic kidney disease (mild and moderate) Depression Diabetes prevention (metabolic syndrome, prediabetes) Glaucoma Hypertension (monitor heart rate) Nephrolithiasis Opioid use Pancreatitis (monitor for symptoms; avoid if prior or current disease) Post-bariatric surgery (data available for 1.8–3.0mg/day) Seizure disorder Type 2 diabetes mellitus Women of reproductive potential (discontinue with pregnancy)

Hypoglycemia Nausea Diarrhea Constipation Vomiting Headache Decreased appetite Dyspepsia Fatigue Dizziness Abdominal pain Increased lipase

This article originally appeared on MPR