New Obesity Guidelines Recommend Nuanced Treatment

This article originally appeared here.
The algorithm categorizes weight-loss medications as "preferred drug," "use with caution," or "avoid" to help clinicians individualize treatment based on a patient's clinical characteristics or coexis
The algorithm categorizes weight-loss medications as "preferred drug," "use with caution," or "avoid" to help clinicians individualize treatment based on a patient's clinical characteristics or coexis

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


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