What medications are used to aid in weight loss?

FDA-Approved Medications for Weight Loss

For patients seeking weight loss medication, GLP-1 receptor agonists such as semaglutide 2.4mg or liraglutide 3.0mg are the most effective first-line options, providing significant weight reduction and cardiovascular benefits. 1

First-Line Options

• GLP-1 receptor agonists (semaglutide 2.4mg, liraglutide 3.0mg) provide robust weight loss with liraglutide showing 5.4% weight reduction at 56 weeks compared to placebo 1
• Semaglutide demonstrates superior efficacy with cardiovascular benefits in people with obesity, making it particularly valuable for patients with increased cardiovascular risk 1, 2
• These medications are especially beneficial for patients with concomitant type 2 diabetes or prediabetes, as they improve glycemic control while promoting weight loss 1, 3
• Common side effects are primarily gastrointestinal (nausea, vomiting, diarrhea) and typically transient 1

Second-Line Options

• Phentermine/topiramate extended-release produces significant weight loss (6.6% at 1 year compared to placebo) 4, 1

  • Available in multiple doses for titration
  • Contraindicated in patients with cardiovascular disease due to sympathomimetic effects 4
  • Common side effects include paresthesia, dizziness, insomnia, and dry mouth 4

• Orlistat inhibits gastrointestinal lipases, preventing absorption of approximately 30% of dietary fat 4

  • Produces modest weight loss (3.1% at 1 year compared to placebo) 4
  • Common side effects include oily spotting, flatus with discharge, fecal urgency 4
  • Good option for patients with hypercholesterolemia who can limit dietary fat intake 4

• Naltrexone/bupropion produces moderate weight loss (4.8% at 56 weeks) 4, 1

  • Side effects include nausea, constipation, headache, and risk of suicidal thoughts 4
  • Particularly beneficial for patients with food cravings, concomitant depression, or those trying to quit smoking 4

Short-Term Options

• Phentermine (monotherapy)
  • Produces 5.1% weight loss at 28 weeks compared to placebo 4
  • Approved for short-term use only 4
  • Common side effects include dry mouth, difficulty sleeping, dizziness, and irritability 4
  • Best for younger patients without cardiovascular disease who need appetite suppression 4

Selection Algorithm

1. Patient Assessment:

   • BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities 4
   • Evaluate for contraindications to specific medications 4

2. First-line therapy for most patients:

   • GLP-1 receptor agonists (semaglutide 2.4mg or liraglutide 3.0mg) 1, 2
   • Particularly beneficial if patient has prediabetes, diabetes, or cardiovascular risk 1

3. Alternative options based on specific patient factors:

   • For patients with cardiovascular disease: Avoid sympathomimetics (phentermine, phentermine/topiramate); use GLP-1 RAs or orlistat 4, 1
   • For patients with hypercholesterolemia: Consider orlistat 4
   • For patients with depression or food cravings: Consider naltrexone/bupropion 4
   • For younger patients needing appetite suppression without CVD: Consider phentermine (short-term) 4

4. Monitoring and follow-up:

   • Assess efficacy and safety monthly for first 3 months, then quarterly 4
   • If <5% weight loss at 12 weeks on maximum tolerated dose, discontinue and consider alternative medication 4

Important Considerations

• Medications should always be used in conjunction with lifestyle modifications including diet and exercise 4, 1
• Obesity is a chronic disease requiring long-term treatment; patients should understand that medication efficacy is generally 5-10% body weight loss for most options, with newer GLP-1 RAs offering superior results 4, 2
• Semaglutide 2.4mg weekly has emerged as a superior option, producing approximately 15% weight loss at 1 year 2
• The first dedicated cardiovascular outcome trial for an anti-obesity medication (SELECT) is underway with semaglutide 2.4mg, which may further establish weight management as a primary target for cardiometabolic disease control 2

Common Pitfalls

• Failing to recognize obesity as a chronic disease requiring long-term treatment 4
• Using medications alone without comprehensive lifestyle modifications 4
• Not monitoring for medication efficacy (target ≥5% weight loss at 12 weeks) 4
• Prescribing sympathomimetic agents to patients with cardiovascular disease 4
• Inadequate patient education about realistic weight loss expectations and potential side effects 4