Obesity Management

Indications for Medications

GLP-1 receptor agonists are recommended for patients with a BMI ≥ 30 kg/m², regardless of comorbidities, and for patients with a BMI ≥ 27 kg/m² with weight-related comorbidities, as indicated by the American Heart Association, American College of Cardiology, and The Obesity Society 1
The American Gastroenterological Association (AGA) recommends semaglutide 2.4 mg as the first-line medication for weight loss in obese or overweight patients with comorbidities, due to its superior efficacy with mean weight loss of 14.9-17.4% at 68 weeks 2
Phentermine-topiramate ER may be preferentially used in patients with comorbid migraines, with approximately 6.8% weight loss compared to placebo 2
Naltrexone-bupropion ER may be considered for patients attempting smoking cessation or with depression, with approximately 4.0% weight loss compared to placebo 2
Orlistat is the least effective option, with approximately 2.9% weight loss compared to placebo, and is suggested against by the AGA due to limited efficacy and GI side effects 2

The dose titration schedule for semaglutide is as follows:
Week Dose
1-4 0.25 mg weekly
5-8 0.5 mg weekly
9-12 1.0 mg weekly
13-16 1.7 mg weekly
17+ 2.4 mg weekly (maintenance dose) [3]
Semaglutide is administered via subcutaneous injection in the abdomen, thigh, or upper arm, once weekly at any time of day, with or without food, as recommended by the American Gastroenterological Association 2
Liraglutide has a 4-week titration schedule to reach maintenance dose, as suggested by the American Gastroenterological Association 2
Monitor for medication-specific side effects, including GI symptoms, pancreatitis, and gallbladder disease for GLP-1 RAs (semaglutide/liraglutide), blood pressure and heart rate for phentermine/phentermine-topiramate, blood pressure, heart rate, and mood changes for naltrexone-bupropion, and fat-soluble vitamin deficiencies for orlistat 2

GLP-1 receptor agonists are contraindicated in patients with personal/family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, and pregnancy 4, 5
Phentermine and phentermine-topiramate ER should be avoided in patients with cardiovascular disease or uncontrolled hypertension due to cardiovascular safety concerns 2
Women of childbearing potential should use effective contraception when taking phentermine-topiramate ER due to teratogenic effects 2

Regular assessment of efficacy, safety, and lipid profile is necessary for patients on GLP-1 receptor agonist therapy, particularly those with hyperlipidemia 6
The American Diabetes Association recommends evaluating weight loss at 3 months, and considering discontinuing or switching medications if <5% weight loss is achieved, with continued medication use if ≥5% weight loss is achieved 4, 5
Common adverse effects of semaglutide are primarily gastrointestinal, including nausea, vomiting, diarrhea, and constipation, with a 38% higher risk of serious adverse events compared to placebo, according to the Gastroenterology guideline 2

Medications should be used as an adjunct to lifestyle modifications, including diet and exercise, as emphasized by all guidelines 2, 7, 8
The American Diabetes Association recommends considering long-term medication use when weight maintenance is inadequate with lifestyle interventions alone, as weight regain is common after medication discontinuation unless comprehensive lifestyle interventions are maintained 4, 6