What medications are approved for weight loss in patients with obesity or overweight with related conditions?

FDA-Approved Medications for Weight Loss in Obesity or Overweight with Related Conditions

The FDA has approved several medications for weight management in individuals with BMI ≥30 kg/m² or ≥27 kg/m² with obesity-related comorbidities such as type 2 diabetes, hypertension, and dyslipidemia. 1

Classification of Patients Eligible for Weight Loss Medication

Medications for weight loss are indicated for:

• Patients with BMI ≥30 kg/m² (obesity)
• Patients with BMI ≥27 kg/m² with at least one weight-related comorbidity 1

FDA-Approved Medications for Weight Loss

Long-Term Use Medications (>12 weeks)

1. GLP-1 Receptor Agonists

   • Semaglutide (Ozempic, Wegovy): Produces significant weight loss (5.4% at 56 weeks) 2
   • Liraglutide (Saxenda): Produces approximately 5.4% weight loss at 56 weeks 1
   • Tirzepatide (Dual GIP/GLP-1 receptor agonist): Recently approved with superior weight loss efficacy 1

2. Lipase Inhibitor

   • Orlistat (Xenical 120mg, Alli 60mg): Produces approximately 2.89 kg weight loss at 12 months 1, 3

3. Combination Therapies

   • Naltrexone/Bupropion (Contrave): Produces approximately 4.8% weight loss at 56 weeks 1

4. Other

   • Setmelanotide: Approved specifically for rare genetic mutations causing severe obesity 1

Short-Term Use Medications (≤12 weeks)

1. Sympathomimetic/Adrenergic Agents
   • Phentermine: Produces approximately 3.6 kg weight loss at 6 months 1
   • Diethylpropion: Produces approximately 3.0 kg weight loss at 6 months 1
   • Phentermine/Topiramate ER (Qsymia): Produces approximately 6.6% weight loss at 1 year 1

Clinical Considerations for Medication Selection

Prioritization of Medications

For patients with both obesity and type 2 diabetes:

• First-line options: GLP-1 receptor agonists (semaglutide or tirzepatide) due to their superior weight loss efficacy and additional cardiometabolic benefits 1

For patients with obesity and cardiovascular disease:

• Avoid sympathomimetic agents like phentermine and phentermine/topiramate ER
• Safer alternatives: Orlistat or GLP-1 receptor agonists 1

Monitoring and Efficacy Assessment

• Assess efficacy and safety at least monthly for the first 3 months, then quarterly 1
• Consider continuing medication if patient achieves ≥5% weight loss after 3 months 1
• Weight loss medications should always be used in conjunction with lifestyle modifications 1

Important Clinical Caveats

• Contraindications: All approved weight loss medications are contraindicated during pregnancy 1
• Medication interactions: Review current medications as some commonly prescribed drugs (e.g., antidepressants like mirtazapine, antihyperglycemics like insulin) can cause weight gain 1
• Duration of therapy: Most weight loss medications are approved for long-term use, but long-term safety data beyond 1-2 years is limited for many agents 1
• Weight regain: There is limited data about weight regain after medications are withdrawn, highlighting the need for sustained lifestyle modifications 1

Health Benefits of Medication-Induced Weight Loss

Even modest weight loss (5-10%) can provide significant health benefits:

• Improved blood pressure (approximately 3 mmHg reduction in systolic BP)
• Decreased HbA1c (0.6-1% reduction)
• Reduced risk of developing type 2 diabetes
• Improvements in lipid profiles
• Potential benefits for obstructive sleep apnea, MASLD/MASH, and heart failure 1

Common Pitfalls to Avoid

1. Relying solely on medications: Weight loss medications should always be used as an adjunct to lifestyle modifications, not as standalone therapy 1

2. Therapeutic inertia: For patients not reaching goals, reevaluate and intensify treatment approaches 1

3. Inadequate monitoring: Regular follow-up is essential to assess efficacy, side effects, and need for dose adjustments

4. Unrealistic expectations: Communicate that medication-induced weight loss is typically modest (approximately 5% of body weight) but clinically meaningful 1

5. Ignoring sarcopenia risk: With significant weight loss, encourage resistance training and adequate protein intake to prevent muscle loss 1