What medications should be tried first for weight loss when diet and exercise are not effective?

First-Line Medications for Weight Loss When Diet and Exercise Are Not Effective

For patients who have not achieved weight loss goals with diet and exercise alone, phentermine is recommended as the first-line medication due to its established efficacy, safety profile, and extensive clinical experience. 1

Patient Selection for Pharmacotherapy

Pharmacotherapy should be considered when:

• BMI ≥30 kg/m² or
• BMI ≥27 kg/m² with weight-related comorbidities (hypertension, diabetes, dyslipidemia, sleep apnea)
• Diet and exercise alone have failed to achieve weight loss goals

Medication Options in Order of Recommendation

1. Phentermine

• Mechanism: Adrenergic agonist that suppresses appetite
• Dosage: 15-37.5 mg once daily in the morning (can start at 7.5 mg)
• Expected weight loss: 5-6% of body weight at 28 weeks
• Best candidates: Younger patients needing appetite suppression
• Contraindications: Uncontrolled hypertension, coronary disease, hyperthyroidism, glaucoma, anxiety, insomnia, history of drug abuse, recent MAOI use 1

2. Orlistat

• Mechanism: Lipase inhibitor that blocks fat absorption
• Dosage: 120 mg three times daily with meals
• Expected weight loss: 3-5% of body weight at 12 months
• Best candidates: Patients with hypercholesterolemia and/or constipation who can limit dietary fat
• Contraindications: Malabsorption syndromes, GI conditions predisposing to diarrhea 1, 2
• Key consideration: Take a multivitamin once daily at bedtime 2

3. Phentermine/Topiramate ER (Qsymia)

• Mechanism: Combined adrenergic agonist/neurostabilizer
• Dosage: Start at 3.75/23 mg daily, gradually increase as needed
• Expected weight loss: 7-10% of body weight at 56 weeks
• Contraindications: Similar to phentermine, plus history of nephrolithiasis 1

4. Lorcaserin (Belviq)

• Mechanism: Serotonin 2C receptor agonist
• Dosage: 10 mg twice daily
• Expected weight loss: 4-5% of body weight at 52 weeks
• Best candidates: Patients reporting inadequate meal satiety
• Contraindications: Patients on other serotonin-modulating medications, cardiac valvular disease 1

Monitoring and Follow-up

• Assess efficacy and safety monthly for the first 3 months, then every 3 months
• If weight loss is <5% after 12 weeks, consider discontinuing and trying an alternative medication 1
• Most weight loss occurs in the first 6 months 2

Important Considerations

• Realistic expectations: Pharmacotherapy typically produces 5-10% body weight loss in successful patients 1
• Long-term approach: Obesity is a chronic disease requiring long-term treatment 1
• Combination therapy: There is no evidence for increased weight loss with combination therapy 1
• Medication selection: Consider patient comorbidities and medication side effect profiles:
  • For patients with cardiovascular disease: Avoid sympathomimetics (phentermine); consider lorcaserin or orlistat 1
  • For patients with diabetes: Consider GLP-1 analogs and metformin 1

Common Pitfalls to Avoid

1. Discontinuing lifestyle modifications: Medications should always be used as an adjunct to diet and exercise, not as a replacement 1
2. Unrealistic expectations: Set appropriate weight loss goals (5-10% of body weight)
3. Inadequate monitoring: Regular follow-up is essential to assess efficacy and side effects
4. Inappropriate patient selection: Screen for contraindications before prescribing
5. Prolonged use without benefit: If a medication doesn't produce at least 5% weight loss in 12 weeks, consider an alternative approach

Remember that the goal of anti-obesity pharmacotherapy is not only weight loss but also improvement in obesity-related comorbidities such as diabetes, hypertension, and dyslipidemia 1.