What are the first-line FDA-approved medications for weight loss?

First-Line FDA-Approved Medications for Weight Loss

Semaglutide (2.4 mg) is the most effective first-line FDA-approved medication for weight loss, demonstrating superior efficacy with mean weight loss of up to 21% at 72 weeks. 1

FDA-Approved Medications for Weight Loss

Long-Term Use Medications (Primary Options)

• GLP-1 Receptor Agonists

  • Semaglutide (Wegovy) - Most effective with 21% mean weight loss at 72 weeks; also provides cardiovascular benefits in people with obesity 1, 2
  • Tirzepatide - A glucose-dependent insulinotropic polypeptide/GLP-1 agonist with significant weight loss effects 1
  • Liraglutide (Saxenda) - Approved at 3.0 mg daily dose for weight management 1, 3

• Other Long-Term Options

  • Phentermine-topiramate (Qsymia) - Fixed-dose combination targeting multiple signaling pathways 1
  • Naltrexone-bupropion (Contrave) - Combination that activates POMC neurons in the arcuate nucleus 1
  • Orlistat (Xenical/Alli) - Blocks absorption of about 30% of ingested fat 1

Short-Term Use Medications

• Phentermine - FDA-approved for short-term use (≤12 weeks) as an adjunct to lifestyle modifications 4
  • Indicated for patients with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 4
  • Usual adult dose is 15-30 mg daily, taken approximately 2 hours after breakfast 4
  • Contraindicated in patients with cardiovascular disease, hyperthyroidism, glaucoma, and during pregnancy 4

Indications and Patient Selection

• FDA-approved weight loss medications are indicated for individuals with:

  • BMI ≥30 kg/m² or
  • BMI ≥27 kg/m² with one or more obesity-associated comorbid conditions (e.g., type 2 diabetes, hypertension, dyslipidemia) 1

• All medications should be used as adjuncts to:

  • Reduced-calorie eating pattern
  • Increased physical activity
  • Behavioral counseling 1

Efficacy Comparison

• Weight loss effectiveness hierarchy (from most to least effective):
  1. Tirzepatide: ~21% weight loss at 72 weeks 1
  2. Semaglutide 2.4 mg: ~10-15% sustained weight loss for up to 4 years 5
  3. Liraglutide 3.0 mg: ~5-6% weight loss 3
  4. Phentermine-topiramate: Variable weight loss 1
  5. Naltrexone-bupropion: Moderate weight loss 1
  6. Orlistat: Modest weight loss 1

Clinical Decision Algorithm

1. First-line options (for most patients without contraindications):

   • Semaglutide 2.4 mg weekly or Tirzepatide - Preferred due to superior efficacy and cardiovascular benefits 1, 5

2. Alternative first-line options (if GLP-1 RAs contraindicated or unavailable):

   • Phentermine-topiramate or Naltrexone-bupropion 1

3. Short-term option (for quick initiation while arranging long-term therapy):

   • Phentermine (≤12 weeks) 4

4. Budget-conscious option:

   • Orlistat - Available over-the-counter at lower dose (Alli) 1

Monitoring and Continuation

• Assess efficacy and safety at least monthly for the first 3 months and quarterly thereafter 1
• Continue medication beyond reaching weight loss goals to maintain health benefits 1
• Discontinue or change medication if:
  • <5% weight loss after 3 months of treatment
  • Significant safety or tolerability issues arise 1

Important Considerations

• Sudden discontinuation often results in weight regain and worsening of cardiometabolic risk factors 1
• Weight loss of ≥10% provides significant improvements in obesity-related complications including type 2 diabetes, hypertension, and cardiovascular risk factors 6
• Medicare currently excludes coverage of FDA-approved antiobesity medications for obesity alone, creating access barriers 1
• Global shortages of GLP-1 receptor agonists may affect availability 1

Common Pitfalls to Avoid

• Failing to review concomitant medications that may promote weight gain (antipsychotics, some antidepressants, glucocorticoids, β-blockers) 1
• Not continuing medications long-term, leading to weight regain 1
• Inadequate monitoring for side effects, particularly gastrointestinal effects with GLP-1 RAs 3
• Using medications without concurrent lifestyle modifications 1