What are the different weight loss medications available?

FDA-Approved Weight Loss Medications

Semaglutide 2.4 mg (Wegovy) is the most effective first-line weight loss medication, achieving up to 21% weight loss at 72 weeks, and should be your preferred initial choice for most patients with obesity. 1

Long-Term FDA-Approved Medications (>12 weeks use)

GLP-1 Receptor Agonists (Most Effective)

• Semaglutide 2.4 mg (Wegovy): Subcutaneous injection once weekly, achieving 11.4% greater weight loss compared to placebo 2
• Tirzepatide: Dual GIP/GLP-1 receptor agonist with ~21% weight loss at 72 weeks, comparable efficacy to semaglutide 1
• Liraglutide 3.0 mg (Saxenda): Daily subcutaneous injection, 5.4% mean weight loss at 56 weeks 3, with 4.7% greater weight loss than placebo 2
  • Common side effects: nausea (28-44%), diarrhea (21-30%), constipation (11-24%) 2
  • Requires dose escalation from 0.6 mg daily, increasing by 0.6 mg weekly up to 3.0 mg 3

Combination Medications

• Phentermine/Topiramate ER (Qsymia): Fixed-dose combination targeting multiple pathways 3

  • 6.6% mean weight loss at 1 year (8.0% greater than placebo) 3, 2
  • Start 3.75/23 mg daily for 14 days, then 7.5/46 mg; can escalate to maximum 15/92 mg 3
  • Contraindicated in cardiovascular disease, pregnancy, glaucoma, hyperthyroidism 3
  • Side effects: paresthesia, dizziness, dysgeusia, insomnia, constipation 3

• Naltrexone SR/Bupropion SR (Contrave): Activates POMC neurons 3

  • 4.8% mean weight loss at 56 weeks (4.1% greater than placebo) 3, 2
  • Dose escalation: start 1 tablet daily, increase by 1 tablet weekly to maximum 2 tablets twice daily (32/360 mg) 3
  • Side effects: nausea, constipation, dizziness, insomnia, dry mouth 3

Lipase Inhibitor

• Orlistat (Xenical 120 mg/Alli 60 mg): Blocks ~30% of dietary fat absorption 3
  • 3.1% mean weight loss at 1 year (most modest efficacy) 3, 2
  • Taken 3 times daily with fat-containing meals 3
  • Side effects: oily spotting, fecal urgency, fatty stools, fecal incontinence (>25% of patients) 3, 2
  • Requires multivitamin supplementation (fat-soluble vitamins A, D, E, K) 3
  • Available over-the-counter as Alli (60 mg), making it budget-friendly 1

Short-Term FDA-Approved Medications (≤12 weeks)

Sympathomimetic Agents

• Phentermine (Adipex): Adrenergic agonist for appetite suppression 3

  • 5.1% weight loss at 28 weeks (6.0 kg) 3
  • Dosing: 15-37.5 mg once daily in morning, or low-dose 8 mg (Lomaira) up to 3 times daily 3
  • Contraindicated in cardiovascular disease, uncontrolled hypertension, hyperthyroidism, anxiety, insomnia 3
  • Side effects: dry mouth, insomnia, dizziness, irritability, mild increases in heart rate and blood pressure 3

• Diethylpropion: 3.0 kg weight loss at 6 months 3

Other Short-Term Options

• Fluoxetine: 3.15 kg weight loss at 12 months 3
• Bupropion (monotherapy): 2.8 kg weight loss at 6-12 months 3

Indications for Pharmacotherapy

Prescribe weight loss medications for patients with BMI ≥30 kg/m² OR BMI ≥27 kg/m² with weight-related comorbidities (type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea) 3, 1

Critical Requirements

• Always combine with intensive lifestyle modifications (reduced-calorie diet, increased physical activity, behavioral counseling) 1
• Never use medications in isolation 3
• All medications are contraindicated in pregnancy 3

Clinical Decision Algorithm

First-Line Choice

1. Semaglutide 2.4 mg weekly OR Tirzepatide for most patients due to superior efficacy and cardiovascular benefits 1

Alternative First-Line Options

1. Phentermine/topiramate OR Naltrexone/bupropion if GLP-1 agonists unavailable or not tolerated 1

Special Populations

• Patients with cardiovascular disease: Use lorcaserin or orlistat; avoid sympathomimetic agents (phentermine, phentermine/topiramate) 3
• Patients with type 2 diabetes: Prefer GLP-1 analogues (semaglutide, liraglutide, tirzepatide) for dual glycemic and weight benefits 3
• Budget-conscious patients: Orlistat (available OTC as Alli) 1
• Patients with constipation: Orlistat may be beneficial despite GI side effects 3

Monitoring and Efficacy Assessment

• Assess monthly for first 3 months, then quarterly 3, 1
• Discontinue or change medication if <5% weight loss after 3 months at therapeutic dose 3, 1
  • For phentermine/topiramate: discontinue if <3% loss at 12 weeks on 7.5/46 mg or <5% loss at 12 weeks on 15/92 mg 3
  • For lorcaserin: discontinue if <5% loss at 12 weeks 3

Long-Term Management

• Continue medication beyond reaching weight loss goals to maintain benefits 1
• Obesity is a chronic disease requiring indefinite treatment 3, 4
• Sudden discontinuation results in weight regain and worsening cardiometabolic risk factors 1

Critical Pitfalls to Avoid

• Review and minimize concomitant medications causing weight gain: antipsychotics (clozapine, olanzapine, risperidone), some antidepressants (TCAs, paroxetine), glucocorticoids, injectable progestins, gabapentin, pregabalin, β-blockers (atenolol, metoprolol) 3
• Do not prescribe sympathomimetics with MAOIs or within 14 days of MAOI use 3
• Ensure contraception counseling for women of reproductive age on teratogenic medications 3
• Monitor for global GLP-1 agonist shortages affecting availability 1
• Understand Medicare excludes coverage of antiobesity medications for obesity alone, creating access barriers 1