| emaglutide (Wegovy, Ozempic/Rybelsus for T2D) | GLP-1 Receptor Agonist. Mimics the effects of Glucagon-Like Peptide-1 (GLP-1), leading to: 1. Delayed gastric emptying (increased satiety). 2. Reduced glucagon secretion. 3. Increased glucose-dependent insulin secretion. 4. Reduced appetite via CNS effects. | BMI $\ge 30\text{ kg/m}^2$ or BMI $\ge 27\text{ kg/m}^2$ with at least one weight-related comorbidity (e.g., hypertension, T2D, dyslipidemia). | Personal or family history of Medullary Thyroid Carcinoma (MTC), Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), history of severe hypersensitivity to Semaglutide. | Nausea, vomiting, diarrhea, constipation, abdominal pain, headache, fatigue. Risk of pancreatitis, gallbladder disease, and acute kidney injury (due to volume depletion from GI side effects). | $\approx 15\%$ of initial body weight (at the approved 2.4 mg dose for obesity). | Very High. Generally the most expensive per month. (Coverage is often restricted). |
| Phentermine/Topiramate ER (Qsymia) | Phentermine: Sympathomimetic amine (stimulant) that increases release of norepinephrine, suppressing appetite (anorectic). Topiramate: Anticonvulsant that enhances satiety and reduces appetite (MOA not fully known; may involve GABA potentiation). | BMI $\ge 30\text{ kg/m}^2$ or BMI $\ge 27\text{ kg/m}^2$ with at least one weight-related comorbidity. | Pregnancy (Risk of birth defects, requires REMS program), Glaucoma, Hyperthyroidism, MAOI use within 14 days. | Paresthesia ("pins and needles"), dry mouth, constipation, dizziness, insomnia, dysgeusia (taste disturbance). Risk of increased heart rate, kidney stones, and mood/cognitive changes. | 10% to 11% of initial body weight (at the highest dose). | Moderate to High. Cost can vary significantly by insurance coverage. |
| Naltrexone/Bupropion ER (Contrave) | Naltrexone: Opioid antagonist, blocks the self-rewarding feedback loop in the hypothalamus/limbic system related to food craving. Bupropion: Dopamine and norepinephrine reuptake inhibitor, which stimulates POMC neurons to reduce appetite and increase energy expenditure. | BMI $\ge 30\text{ kg/m}^2$ or BMI $\ge 27\text{ kg/m}^2$ with at least one weight-related comorbidity. | Uncontrolled hypertension, Seizure disorder, history of anorexia/bulimia, chronic opioid use (risk of precipitated withdrawal), MAOI use within 14 days, sudden discontinuation of alcohol/sedatives/anticonvulsants. | Nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth. Risk of suicidal thoughts/behavior (due to bupropion component) and increased blood pressure/heart rate. | 5% to 9% of initial body weight (Placebo-subtracted mean weight loss is typically $\approx 4\text{ to }5\text{ kg}$). | Moderate to High. Cost can vary significantly by insurance coverage. |