What medications can be used to reduce weight?

Medications for Weight Loss

GLP-1 receptor agonists like semaglutide 2.4mg are the most effective medications for weight loss, producing up to 15% weight loss at 1 year while improving cardiovascular risk factors. 1, 2

First-Line Medications

• GLP-1 Receptor Agonists: These medications provide the most robust weight loss and have cardiovascular benefits:

  • Semaglutide 2.4mg weekly (Wegovy): Produces approximately 15% weight loss at 1 year 2
  • Liraglutide 3.0mg daily (Saxenda): Produces approximately 5.4% weight loss at 56 weeks 1
  • Particularly beneficial for patients with metabolic syndrome, type 2 diabetes, or prediabetes 1, 3
  • Side effects are primarily gastrointestinal and typically transient 1

• Phentermine/Topiramate Extended-Release (Qsymia):

  • Produces significant weight loss (6.6% at 1 year compared to placebo) 1
  • Available in multiple doses for titration 1
  • Contraindicated in patients with cardiovascular disease due to sympathomimetic effects 1, 4

Second-Line Medications

• Orlistat (Xenical 120mg prescription, Alli 60mg OTC):

  • Inhibits gastrointestinal lipases, preventing absorption of approximately 30% of dietary fat 5
  • Produces modest weight loss (2.89kg at 12 months) 5
  • Common side effects include gastrointestinal issues related to fat malabsorption 5, 1
  • Available over-the-counter at lower doses 6

• Phentermine (short-term use):

  • FDA-approved for short-term (a few weeks) use for weight management 4
  • Produces modest weight loss (3.6kg at 6 months) 5
  • Dosage: 15-37.5mg once daily in the morning 5
  • Contraindicated in patients with cardiovascular disease, hyperthyroidism, glaucoma 4

• Naltrexone/Bupropion (Contrave):

  • Produces moderate weight loss (4.8% at 56 weeks) 1
  • Side effects include increased gastrointestinal effects, risk of suicidal thoughts and behaviors, and seizures 1

• Other Options:

  • Diethylpropion: Produces modest weight loss (3.0kg at 6 months) 5
  • Fluoxetine: Higher doses (60mg) can produce weight loss (3.15kg at 12 months) 5
  • Bupropion: Produces modest weight loss (2.8kg at 6-12 months) 5

Patient Selection Algorithm

1. For patients with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 5, 1:

   • First try lifestyle modifications (diet and exercise)
   • If unsuccessful after adequate trial, add pharmacotherapy

2. For patients with cardiovascular disease or risk factors:

   • Choose GLP-1 receptor agonists (semaglutide or liraglutide) 1, 2
   • Avoid sympathomimetics (phentermine, phentermine/topiramate) 1, 4

3. For patients with type 2 diabetes:

   • Prioritize GLP-1 receptor agonists for dual benefit of glycemic control and weight loss 1, 3

4. For patients with dyslipidemia:

   • Consider orlistat for additional benefit through improvement in lipid profiles 1

5. For patients with limited insurance coverage:

   • Consider phentermine (most cost-effective) or orlistat (available OTC at lower dose) 6

Monitoring and Expectations

• Assess efficacy and safety monthly for the first 3 months, then every 3 months 1
• Expect 5-10% body weight loss in most successful patients 5
• If less than 5% weight loss after 12 weeks on maximum tolerated dose, consider switching medications 1
• Weight regain is common after medication discontinuation, highlighting the need for sustained lifestyle modifications 5

Important Considerations

• All weight loss medications should be used as adjuncts to lifestyle modifications including diet and exercise 5, 4
• The goal of anti-obesity pharmacotherapy is not only weight reduction but also improvement of obesity-related comorbidities 5, 1
• Long-term safety and efficacy data beyond 1-2 years are limited for most medications 5
• Medication selection should be based on comorbidities, contraindications, side effect profiles, and patient preferences 5, 1
• Pregnancy and nursing are contraindications for weight loss medications 4, 7