Endocrine

American Gastroenterology Association (AGA) Clinical Practice Obesity Guideline Including Pharmacological Interventions

Summary:

Obesity, defined by the CDC as a weight that is higher than what is considered healthy for a given height, has been increasing in prevalence over several decades. Roughly two thirds of adults are considered obese or overweight, with a recent estimate putting the prevalence of adults with obesity at nearly 42% of the population. It is customary to use BMI calculations as both a screening tool and to further characterize the degree of obesity, but it is important to note that BMI does not diagnose a patient’s health or even degree of body fat. Healthcare providers should combine appropriate clinical assessments, considering body weight, central fat distribution, functional status, and presence of obesity related complications, to create a more accurate picture of a patient’s health. In recent years we have gained a better understanding of what contributes to obesity and what helps a patient maintain a healthy weight. The AGA has accordingly updated their guidelines on pharmacological interventions for adults with obesity to better help clinicians care for their obese patients.

Diagnosis

All adults should be screened for obesity by obtaining a height and weight and calculating BMI during a routine physical exam

Adult BMI Calculator

BMI can be calculated via calculator or by dividing weight (kg) over height (m)²

Underweight: <18.5 kg/m²
Normal weight: ≥18.5 to 24.9 kg/m²
Overweight: ≥25.0 to 29.9 kg/m²
Obesity: ≥30 kg/m²

Obesity can be further characterized by class

Class I: 30.0 to 34.9 kg/m²
Class II: 35.0 to 39.9 kg/m²
Class III: ≥40 kg/m²

A BMI over 25 kg/m² should prompt further evaluation including

Measurement of waist circumference: > 40 inches in men and > 35 inches in women is associated with increased risk for obesity related complications
Screening for obesity related complications (see below)
Consideration of causes of weight gain not related to diet and activity level (e.g., hypothyroidism, drug side effect, depression, Cushing’s syndrome)
Blood pressure measurement
Fasting glucose and lipid levels

Note: A BMI > 23 kg/m² may indicate the need for further evaluation in patients of South Asian, Southeast Asian, and East Asian descent as obesity related complications develop at lower BMIs in these populations

Obesity related complications

Type 2 Diabetes Mellitus (T2DM), Prediabetes
Cardiovascular disease
Hypertension
Hyperlipidemia
Obstructive sleep apnea
Obesity hypoventilation syndrome
Nonalcoholic fatty liver disease
Osteoarthritis
Stroke
Certain malignancies (e.g., colorectal cancer, endometrial cancer)
Depression
PCOS, Infertility
GERD
Urinary incontinence
VTE
Gallstones

Lifestyle Interventions

The cornerstones of weight loss management are individualized dietary changes and increased physical activity. Recent guidelines, including the USPSTF recommendations, recommend the use of behavioral therapy and a multidisciplinary approach involving weight loss counselors, psychologists, physical therapists and dieticians to assist the patient in establishing and reaching their weight loss goals.

Weight loss goals should be modest

A weight reduction of 5% to 10% of initial body weight is sufficient to yield significant health benefits including decreased risk of diabetes and cardiovascular disease
A 5% weight loss within 3 months is used by the US Food and Drug Administration (FDA) to assess the efficacy of medications to treat obesity

Increased calorie expenditure

Adults should perform at least 150 minutes of moderate-intensity or 75 minutes of vigorous-intensity aerobic activity per week (or an equivalent combination of these)

Decreased calorie intake

Reducing daily calorie intake to 1200 to 1500 for women and 1500 to 1800 for men
Estimating an individual’s daily energy requirements and aiming for an energy deficit of 500 kcal/d or 750 kcal/d

Pharmacological Therapies

In adults with obesity or overweight with weight-related complications, who have had an inadequate response to lifestyle interventions, the AGA recommends adding pharmacological agents to lifestyle interventions over continuing lifestyle interventions alone.

Clinical Considerations

Anti-obesity medications (AOMs) are not recommended for:

Pregnant women
Patients with bulimia nervosa

Use caution when starting AOMs for patients with:

Diabetes treated with insulin or insulin secretagogues (e.g., sulfonylureas) as AOMs may decrease blood sugar levels
Hypertension or those on blood pressure lowering agents, as AOMs may lower blood pressure as weight is lost
Binge eating disorder

Cost of AOMs may limit their access and data on cost-effectiveness is limited

Recommended Anti-Obesity Medications

Semaglutide (Wegovy)

Largest magnitude of net benefit, so can be considered first line prior to other drugs
Dosing is started at 0.25 mg/week escalated gradually to goal of 2.4 mg/week
Delays gastric emptying, may cause nausea and emesis which is mitigated by slow taper to goal dose
Can maintain on highest dose tolerated
Contraindications: History of pancreatitis|Hx or FHx of Medullary Thyroid Cancer| Hx of FHx of MEN-2A or MEN-2B
Associated with increased risk of pancreatitis and biliary disease
Used in Diabetes under brand name Ozempic

Liraglutide (Saxenda)

Escalate dose gradually to a target dose of 3mg daily
Can maintain at highest dose tolerated
Associated with nausea, emesis due to delayed gastric emptying
Associated with increased risk of pancreatitis and biliary disease
Contraindications: History of pancreatitis or FHx of Medullary Thyroid Cancer| Hx of FHx of MEN-2A or MEN-2B
Used in DM under brand name Victoza

Tirzepatide (Mounjaro)

Not included in AGA guidelines, but promising results from recent trial published in NEJM (see “Primary Sources – Learn More” below)

Phentermine-Topiramate ER (Qsymia)

Useful in patients who also have migraines given the Topamax component
Avoid in patients with cardiovascular disease and hypertension
Monitor HR and BP regularly while on this medicine
Topamax is teratogenic and women of child-bearing age should be appropriately counseled
Pregnancy test should be obtained prior to initiation
Multiple drug interactions exist

Naltrexone-Bupropion ER (Contrave)

Useful in patients with concomitant depression or desire to quit smoking
Avoid in patients with seizure disorders and those on opiates
Monitor HR and BP regularly while on this medicine

Orlistat (Xenical)

No longer recommended due to minimal effects and significant GI adverse effects

Phentermine (Adipex)

Approved by the FDA for short term use (12 weeks) but used off label for chronic weight loss management
Typically not recommended as first line therapy due to side effects and potential for abuse
Avoid in patients with cardiovascular disease
Avoid in patients with history of drug abuse
Monitor HR and BP regularly while on this medicine

Diethylpropion (Amfepramone)

Approved by the FDA for short term use (12 weeks) but used off label for chronic weight loss management
Typically not recommended as first line therapy due to side effects and potential for abuse
Avoid in patients with cardiovascular disease
Monitor HR and BP regularly while on this medicine

Future therapies

Gelesis100 Oral Superabsorbent hydrogel

Space occupying gel to decrease appetite and PO intake
Delivered in the form of a pill with 3 pills take with water prior to lunch and dinner
For patients with BMI of 25 to 40 kg/m²
Currently in use via clinical trials