What medications are used for appetite suppression in weight management?

FDA-Approved Medications for Appetite Suppression in Weight Management

The most effective FDA-approved medications for appetite suppression in weight management include phentermine, phentermine/topiramate ER, liraglutide, naltrexone/bupropion SR, and orlistat, with phentermine/topiramate ER demonstrating the highest efficacy for weight loss at 6.8% greater than placebo. 1, 2

First-Line Appetite Suppressant Medications

Phentermine

• Mechanism: Adrenergic agonist that activates the sympathetic nervous system, increasing norepinephrine release
• Dosage: 15-37.5 mg orally once daily (morning), individualized to lowest effective dose
• Efficacy: Short-term appetite suppression
• Limitations: FDA-approved only for short-term use (≤12 weeks), though often prescribed off-label for longer periods
• Contraindications: Cardiovascular disease, hyperthyroidism, glaucoma, agitated states, history of drug abuse, pregnancy, nursing, MAOIs use 1, 3
• Side effects: Dry mouth, insomnia, irritability, constipation 1

Phentermine/Topiramate ER (Qsymia)

• Mechanism: Combination of adrenergic agonist with neurostabilizer (topiramate)
• Dosage: Gradual titration from 3.75/23 mg to 7.5/46 mg daily, up to 15/92 mg daily
• Efficacy: 6.8% greater weight loss than placebo in clinical trials 2, 4
• Discontinuation criteria: If <3% weight loss after 12 weeks at 7.5/46 mg or <5% after 12 weeks at 15/92 mg
• Side effects: Paresthesia, dizziness, insomnia, constipation, dry mouth 1
• Best for: Younger patients needing appetite suppression 1

Liraglutide (Saxenda)

• Mechanism: GLP-1 receptor agonist that reduces appetite and increases satiety
• Dosage: Titration from 0.6 mg daily to 3.0 mg daily over 5 weeks
• Efficacy: 5.4% greater weight loss than placebo 5, 4
• Side effects: Nausea, vomiting, diarrhea, constipation 1, 2
• Best for: Patients with inadequate meal satiety, prediabetes, or type 2 diabetes 1

Second-Line Appetite Suppressant Medications

Naltrexone/Bupropion SR (Contrave)

• Mechanism: Opioid receptor antagonist combined with dopamine/norepinephrine reuptake inhibitor
• Dosage: Titration from 8/90 mg daily to 16/180 mg twice daily over 4 weeks
• Efficacy: 4.0% greater weight loss than placebo 5, 4
• Discontinuation criteria: If <5% weight loss at 12 weeks
• Side effects: Nausea, constipation, headache, vomiting 1
• Best for: Patients with food cravings or addictive eating behaviors 1

Orlistat (Xenical/Alli)

• Mechanism: Lipase inhibitor that blocks fat absorption (not primarily an appetite suppressant)
• Dosage: 120 mg (Rx) or 60 mg (OTC) three times daily with meals
• Efficacy: 2.9% greater weight loss than placebo 5, 4
• Side effects: Oily spotting, flatus with discharge, fecal urgency 1
• Best for: Patients with hypercholesterolemia or constipation who can limit dietary fat 1

Clinical Decision Algorithm for Medication Selection

1. Assess patient BMI and comorbidities:

   • BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities

2. Screen for contraindications to specific medications:

   • Cardiovascular disease → avoid phentermine and phentermine/topiramate
   • History of pancreatitis → avoid liraglutide
   • Seizure disorder → avoid naltrexone/bupropion
   • Malabsorption syndromes → avoid orlistat

3. Match medication to patient characteristics:

   • Need for rapid appetite suppression → phentermine or phentermine/topiramate
   • Type 2 diabetes or prediabetes → liraglutide
   • Food cravings/addictive eating → naltrexone/bupropion
   • Hypercholesterolemia → orlistat

4. Monitor efficacy and safety:

   • Evaluate weight loss at 12 weeks
   • Discontinue if inadequate response per medication-specific criteria
   • Monitor for side effects and adjust dosing as needed

Important Considerations and Pitfalls

• Combination therapy: Combining multiple weight loss medications is not recommended due to lack of safety and efficacy data 1

• Medication interactions: Screen for potential interactions, particularly with:

  • MAOIs (contraindicated with phentermine)
  • Serotonergic drugs (caution with lorcaserin)
  • Opioids (contraindicated with naltrexone/bupropion)

• Psychiatric medications: Be aware that many psychiatric medications can cause weight gain; bupropion is the only antidepressant consistently associated with weight loss 1

• Discontinued medications: Lorcaserin (Belviq) was withdrawn from the market in 2020 due to increased cancer risk 5, 4

• Long-term use: While most clinical trials show continued efficacy beyond the FDA-approved duration, the long-term safety profile varies by medication 1, 4