What are the current medications for weight loss?

Current Weight Loss Medications

The most current FDA-approved weight loss medications include phentermine, orlistat, phentermine/topiramate ER, lorcaserin, naltrexone/bupropion SR, liraglutide 3.0 mg, semaglutide 2.4 mg, and tirzepatide. 1, 2

FDA-Approved Weight Loss Medications

Short-term Use

• Phentermine (Adipex):
  • Adrenergic agonist with average weight loss of 5.1% at 28 weeks
  • Dosage: 15-37.5 mg daily
  • Only approved for short-term use (a few weeks)
  • Contraindicated in patients with cardiovascular disease 3, 1, 4

Long-term Use

• Orlistat (Xenical/Alli):

  • Lipase inhibitor with average weight loss of 2.89 kg at 12 months
  • Dosage: 120 mg three times daily with meals
  • Side effects: Oily spotting, flatus with discharge, fecal urgency 3, 1

• Phentermine/topiramate ER (Qsymia):

  • Combination therapy with average weight loss of 6.6% at 1 year
  • Requires gradual dose escalation
  • Contraindicated in patients with cardiovascular disease 3, 1

• Lorcaserin (Belviq):

  • Serotonin receptor agonist with average weight loss of 3.6% at 1 year
  • Dosage: 10 mg twice daily
  • Safer alternative for patients with cardiovascular disease 3, 1

• Naltrexone/bupropion SR (Contrave):

  • Opioid antagonist/dopamine-norepinephrine reuptake inhibitor
  • Average weight loss of 4.8% at 56 weeks
  • Requires gradual dose escalation 3, 1

• Liraglutide 3.0 mg (Saxenda):

  • GLP-1 analog with average weight loss of 5.4% at 56 weeks
  • Particularly useful in patients with type 2 diabetes
  • Administered via subcutaneous injection 3, 1

• Semaglutide 2.4 mg (Wegovy):

  • GLP-1 receptor analog with superior efficacy
  • Average weight loss of 15% at 1 year
  • Weekly subcutaneous injection 5, 2

• Tirzepatide:

  • Recently approved medication showing promise for even greater weight loss 5, 2

Indications for Pharmacotherapy

Pharmacotherapy should be considered for:

• BMI ≥30 kg/m² without comorbidities
• BMI ≥27 kg/m² with weight-related comorbidities (hypertension, type 2 diabetes, dyslipidemia, sleep apnea) 3, 1

Treatment Algorithm

1. First-line treatment: Intensive lifestyle modifications (diet, exercise, behavioral therapy) for 3 months

2. If inadequate response (weight loss <5% after 3 months):

   • Add pharmacotherapy based on patient profile:
     • For patients with cardiovascular disease: Avoid sympathomimetic agents (phentermine, phentermine/topiramate ER); consider lorcaserin or orlistat 3
     • For patients with type 2 diabetes: Consider GLP-1 analogs (liraglutide, semaglutide) 3

3. Monitoring:

   • Assess efficacy and safety monthly for the first 3 months, then every 3 months
   • Discontinue medication if:
     • Weight loss <5% after 12 weeks at maximum tolerated dose
     • Serious adverse effects occur 1

Important Considerations

• All medications should be used as adjuncts to lifestyle modifications, never alone 1
• Weight loss attributable to medications is modest (3-10% for most medications, up to 15% for semaglutide) 1, 5
• Continued use of medication is required to maintain weight loss 6
• Avoid using non-FDA approved agents or combinations of weight loss medications 4
• Sibutramine and ephedra weight loss preparations should be avoided, particularly in patients with heart failure 3

Real-World Efficacy Comparison

In real-world settings, the percentage of patients achieving ≥5% weight loss within 6 months varies by medication:

• Phentermine: 87.2%
• Phentermine/topiramate: 67.7%
• Liraglutide: 58.1%
• Naltrexone/bupropion: 35.3%
• Lorcaserin: 75%
• Orlistat: 50% 7

The newer GLP-1 receptor analogs (semaglutide 2.4 mg and tirzepatide) represent the most significant advancement in obesity pharmacotherapy, offering substantially greater weight loss than previous medications 5, 2.