What are the recommended weight loss medications for obese or overweight patients with comorbidities?

Recommended Weight Loss Medications for Obese or Overweight Patients with Comorbidities

For obese or overweight patients with comorbidities, GLP-1 receptor agonists (semaglutide and liraglutide) are the most effective weight loss medications, with semaglutide demonstrating superior efficacy with mean weight loss of 14.9-17.4% at 68 weeks compared to other available options. 1

Patient Selection Criteria

Weight loss medications should be considered for:

• Patients with BMI ≥30 kg/m² (regardless of comorbidities)
• Patients with BMI ≥27 kg/m² with at least one weight-related comorbidity (e.g., type 2 diabetes, hypertension, dyslipidemia) 2

First-Line Medication Options (In Order of Efficacy)

1. GLP-1 Receptor Agonists

   • Semaglutide 2.4mg weekly (preferred)

     • Most effective with 14.9-17.4% mean weight loss at 68 weeks
     • 64.9% of patients achieve ≥10% weight loss
     • Weekly injection (more convenient than daily)
     • Titration schedule: 0.25mg (weeks 1-4) → 0.5mg (weeks 5-8) → 1.0mg (weeks 9-12) → 1.7mg (weeks 13-16) → 2.4mg (week 17+) 1

   • Liraglutide 3.0mg daily

     • 5-6% mean weight loss
     • Approximately 33% of patients achieve ≥10% weight loss
     • Daily injection
     • 4-week titration schedule 1

2. Phentermine/Topiramate ER

   • 6.8% mean weight loss 3, 4
   • Recommended dose: 7.5mg/46mg daily 2

3. Naltrexone/Bupropion ER

   • 4.0% mean weight loss 3, 4

4. Orlistat

   • 2.9% mean weight loss 3, 4
   • Dose: 120mg three times daily with meals 5
   • Less effective than other options but may be suitable for patients who cannot use injectable medications

Special Considerations for Comorbidities

Type 2 Diabetes

• Preferred: GLP-1 receptor agonists (semaglutide or liraglutide)
  • Provide dual benefits of weight loss and glycemic control
  • Liraglutide shows modest HbA1c reduction (0.5-0.93%) 1
  • Consider in patients with established cardiovascular disease or high cardiovascular risk 1

Cardiovascular Disease

• Preferred: GLP-1 receptor agonists
  • Provide cardiovascular benefits beyond weight loss 1
  • Avoid phentermine in patients with history of cardiovascular disease, uncontrolled hypertension, or arrhythmias 6

Hypertension

• Avoid: Phentermine in patients with uncontrolled hypertension 6
• Consider: GLP-1 receptor agonists or orlistat

Chronic Kidney Disease

• Preferred: GLP-1 receptor agonists 1
• Dose adjustment: Phentermine requires dose adjustment (max 15mg daily) for severe renal impairment (eGFR 15-29 mL/min/1.73m²)
• Avoid phentermine if eGFR <15 mL/min/1.73m² 6

Monitoring and Follow-Up

1. Efficacy Assessment:

   • Evaluate weight loss at 3 months
   • If <5% weight loss is achieved, consider discontinuing or switching medications 2
   • Continue medication if ≥5% weight loss is achieved

2. Safety Monitoring:

   • GLP-1 receptor agonists: Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea), pancreatitis, and gallbladder disease 1
   • Phentermine: Monitor blood pressure and heart rate periodically 6
   • Orlistat: Monitor for fat-soluble vitamin deficiencies; recommend daily multivitamin taken 2 hours apart from orlistat 2

Common Pitfalls and Caveats

1. Medication-induced weight gain:

   • Review and minimize medications that promote weight gain (e.g., certain antidiabetics, antidepressants, antipsychotics, antiepileptics) 2
   • Consider weight-neutral alternatives when possible

2. Short-term vs. long-term use:

   • Phentermine is FDA-approved for short-term use only (a few weeks) 6
   • Other medications (GLP-1 receptor agonists, phentermine/topiramate, naltrexone/bupropion, orlistat) are approved for long-term use 2

3. Contraindications:

   • GLP-1 receptor agonists: Contraindicated in patients with personal/family history of medullary thyroid carcinoma, multiple endocrine neoplasia type 2, and pregnancy 1
   • Phentermine: Contraindicated in cardiovascular disease, hyperthyroidism, glaucoma, agitated states, history of drug abuse, pregnancy, and nursing 6

4. Weight regain:

   • Weight regain is common after medication discontinuation unless comprehensive lifestyle interventions are maintained 2
   • Consider long-term medication use when weight maintenance is inadequate with lifestyle interventions alone 2

5. Compounded GLP-1 receptor agonists:

   • Lack FDA approval, standardized quality control, and evidence for safety and efficacy
   • Should not be used for treatment of obesity 1

Weight loss medications should always be used as adjuncts to comprehensive lifestyle interventions including diet, physical activity, and behavioral strategies for optimal and sustainable results.