What oral medications are available for weight loss?

Oral Medications for Weight Loss

Several FDA-approved oral medications are available for weight loss, including phentermine, orlistat, phentermine/topiramate (Qsymia), lorcaserin (Belviq), naltrexone/bupropion (Contrave), and fluoxetine and bupropion off-label, each with modest efficacy of approximately 3-5 kg weight loss over placebo when combined with lifestyle modifications. 1

Medication Options and Efficacy

Short-term Use (≤12 weeks)

• Phentermine
  • Mechanism: Adrenergic agonist (appetite suppressant)
  • Efficacy: 5.1% weight loss at 28 weeks 1
  • Dosage: 15-37.5 mg daily in the morning 1
  • Best for: Younger patients without cardiovascular disease or uncontrolled hypertension 1

Long-term Use (>12 weeks)

• Orlistat (Xenical/Alli)

  • Mechanism: Lipase inhibitor (blocks fat absorption)
  • Efficacy: 2.89 kg weight loss at 12 months 1
  • Dosage: 120 mg three times daily with meals (prescription) or 60 mg three times daily (over-the-counter) 1
  • Side effects: Oily spotting, flatus with discharge, fecal urgency 1

• Phentermine/Topiramate (Qsymia)

  • Mechanism: Adrenergic agonist/neurostabilizer
  • Efficacy: 6.6% weight loss at 1 year 1
  • Dosage: Starting at 3.75/23 mg daily with gradual dose escalation 1

• Lorcaserin (Belviq)

  • Mechanism: 5-HT2C receptor agonist
  • Efficacy: 3.6% weight loss at 1 year 1
  • Dosage: 10 mg twice daily 1
  • Safer option for patients with cardiovascular disease 1

• Naltrexone/Bupropion (Contrave)

  • Mechanism: Opioid receptor antagonist/dopamine and norepinephrine reuptake inhibitor
  • Efficacy: 4.8% weight loss at 56 weeks 1
  • Dosage: Gradual dose escalation to 16/180 mg twice daily 1

• Off-label options:

  • Fluoxetine: 3.15 kg weight loss at 12 months (60 mg dose) 1
  • Bupropion: 2.77 kg weight loss at 6-12 months 1

Patient Selection Algorithm

1. Determine eligibility:

   • BMI ≥30 kg/m² or
   • BMI ≥27 kg/m² with weight-related comorbidities (hypertension, type 2 diabetes, dyslipidemia, sleep apnea) 1

2. Assess contraindications:

   • For sympathomimetics (phentermine, phentermine/topiramate):
     • Cardiovascular disease
     • Uncontrolled hypertension
     • Hyperthyroidism
     • Glaucoma
     • During or within 14 days of MAOIs 2

3. Match medication to patient profile:

   • Patients with cardiovascular disease: Choose lorcaserin or orlistat 1
   • Patients with type 2 diabetes: Consider GLP-1 agonists 1
   • Patients with anxiety/insomnia: Avoid phentermine 1

Monitoring and Expectations

1. Set realistic expectations:

   • Modest weight loss of 3-5 kg over placebo at 1 year 1
   • Even modest weight loss (5-10%) can significantly improve obesity-related comorbidities 3

2. Monitoring protocol:

   • Assess efficacy and safety monthly for first 3 months, then quarterly 1
   • Continue medication if ≥5% weight loss achieved at 3 months 1
   • Discontinue if <5% weight loss at 3 months or significant side effects 1

Important Considerations

• Adjunctive therapy: All medications should be used as adjuncts to diet, exercise, and behavioral modifications, not as standalone treatments 1, 4

• Duration of therapy: Limited long-term safety data beyond 12 months for most medications (except orlistat) 1

• Weight regain: Weight regain is common after discontinuation, emphasizing the need for sustained lifestyle modifications 1

• Cost-effectiveness: While medications add cost to treatment, they may be cost-effective when considering improvements in obesity-related comorbidities 3

Common Pitfalls to Avoid

1. Unrealistic expectations: Medications typically produce modest weight loss (5-10%), not dramatic results 4

2. Monotherapy: Using medications without concurrent lifestyle modifications significantly reduces effectiveness 5

3. Inappropriate patient selection: Prescribing sympathomimetics to patients with cardiovascular disease increases risk 1

4. Inadequate monitoring: Failure to assess efficacy at 3 months may result in unnecessary continued exposure to side effects 1

5. Ignoring comorbid conditions: Some medications used to treat other conditions (antipsychotics, some antidepressants, glucocorticoids) can cause weight gain and should be minimized when possible 1

By selecting the appropriate medication based on patient characteristics and comorbidities, setting realistic expectations, and using medications as part of a comprehensive approach that includes lifestyle modifications, oral medications can be effective tools in managing obesity and reducing obesity-related health risks.