What are the recommended weight loss medications and their dosages?

Weight Loss Medications: Recommended Options and Dosing

For chronic weight management in adults with BMI ≥27 kg/m² with comorbidities or BMI ≥30 kg/m², GLP-1 receptor agonists (semaglutide or liraglutide) are the most effective first-line pharmacotherapy options, achieving 11-12% weight loss compared to 3-7% with older agents. 1, 2

FDA-Approved Medications for Long-Term Use

GLP-1 Receptor Agonists (First-Line)

Liraglutide 3.0 mg (Saxenda)

• Starting dose: 0.6 mg subcutaneous daily for 1 week 3
• Titration: Increase by 0.6 mg weekly until reaching 3.0 mg daily 3
• Expected weight loss: 5.4% placebo-subtracted weight reduction 4
• Discontinuation criteria: Stop if <4% weight loss after 16 weeks 3
• Side effects: Nausea (28-44%), diarrhea (21-30%), constipation (11-24%) 2
• Advantages: Improves hepatic steatosis in NAFLD patients and provides cardiometabolic benefits 1, 2

Semaglutide 2.4 mg

• Expected weight loss: 11.4% placebo-subtracted weight reduction 2
• Most potent currently available medication for weight loss among non-tirzepatide options 2, 5

Combination Medications (Second-Line)

Phentermine/Topiramate ER (Qsymia)

• Starting dose: 3.75/23 mg daily for 14 days 3
• Standard dose: 7.5/46 mg daily after initial 2 weeks 3
• Maximum dose: 15/92 mg daily (can escalate through 11.25/69 mg) 3
• Timing: Take once daily in the morning 3
• Expected weight loss: 6.8% placebo-subtracted weight reduction 4
• Discontinuation criteria: Stop if <3% weight loss after 12 weeks at 7.5/46 mg dose, or <5% weight loss after 12 weeks at maximum dose 3
• Contraindications: Women of reproductive potential must use reliable contraception due to teratogenicity risk 3

Naltrexone SR/Bupropion SR (Contrave)

• Starting dose: 1 tablet (8 mg naltrexone/90 mg bupropion) daily 3
• Titration: Increase by 1 tablet weekly 3
• Maximum dose: 2 tablets twice daily (32/360 mg total daily) 3
• Expected weight loss: 4.0-4.8% placebo-subtracted weight reduction 1, 4
• Discontinuation criteria: Stop if <5% weight loss after 12 weeks 3
• Side effects: Constipation in approximately 20% of patients 2

Lipase Inhibitor (Alternative Option)

Orlistat (Xenical/Alli)

• Prescription dose (Xenical): 120 mg three times daily with each fat-containing meal 3
• OTC dose (Alli): 60 mg three times daily with each fat-containing meal 3, 6
• Expected weight loss: 2.9-3.1% placebo-subtracted weight reduction 6, 4, 2
• Dietary requirement: Follow diet with approximately 30% calories from fat 3
• Required supplementation: Take daily multivitamin due to decreased absorption of fat-soluble vitamins A, D, E, and K 3
• Side effects: Abdominal pain, oily spotting, fecal urgency, flatulence in >25% of patients, especially with high-fat meals 6, 2
• Contraindications: Chronic malabsorption syndrome or cholestasis 6
• Advantages: Only FDA-approved OTC weight loss medication with substantial evidence 6

Short-Term Use Only

Phentermine (monotherapy)

• Dose range: 15-37.5 mg orally once daily 3
• Practical dosing: Start with 9.375 mg (quarter tablet) or 18.75 mg (half tablet); can use split dosing of half tablet twice daily 3
• Duration: FDA-approved for ≤12 weeks only 3
• Mechanism: Adrenergic agonist that increases resting energy expenditure and suppresses appetite 3
• Contraindications: Avoid in patients with cardiovascular disease 1

Clinical Decision Algorithm

Step 1: Assess Patient Eligibility

• BMI ≥27 kg/m² with obesity-related comorbidities (type 2 diabetes, hypertension, dyslipidemia) OR BMI ≥30 kg/m² 3
• Must be combined with lifestyle modifications (diet, physical activity, behavioral counseling) 3, 6

Step 2: Select First-Line Agent

• Prefer GLP-1 agonists (liraglutide or semaglutide) for patients with type 2 diabetes, NAFLD, or requiring maximal weight loss 1, 2
• Consider phentermine/topiramate ER if GLP-1 agonists are cost-prohibitive or not tolerated 3, 4
• Consider orlistat for patients with constipation or those preferring OTC options with lower cost 3, 6

Step 3: Monitor Response

• Assess monthly for first 3 months, then every 3 months 3, 6
• Discontinue if inadequate response: <5% weight loss after 3 months for most agents (except liraglutide: <4% at 16 weeks) 3, 6
• Continue if effective: ≥5% weight loss typically predicts further success with continued use 3

Critical Safety Considerations

Avoid These Combinations:

• Never combine multiple weight-loss medications without specific evidence 3
• Do not use with monoamine oxidase inhibitors 7
• Avoid sympathomimetic agents (phentermine) in cardiovascular disease 1

Pregnancy and Reproductive Health:

• All weight-loss medications are contraindicated in pregnancy 3
• Women of reproductive potential require reliable contraception, especially with phentermine/topiramate 3

Diabetes Management:

• Adjust insulin and oral hypoglycemic doses when initiating weight-loss medications to prevent hypoglycemia 3
• GLP-1 agonists provide dual benefit of weight loss and glycemic control 3, 1

Rapid Weight Loss Warning:

• Avoid weight loss >1 kg/week in patients with NAFLD to prevent worsening portal inflammation and fibrosis 1

Common Pitfalls to Avoid

• Failing to discontinue ineffective therapy: If weight loss goals are not met by 12-16 weeks, switch agents rather than continuing ineffective treatment 3, 6
• Inadequate lifestyle intervention: Medications are adjuncts only; they fail without concurrent dietary changes and physical activity 3, 6
• Ignoring medication effects on comorbidities: Minimize medications for other conditions that promote weight gain (antipsychotics, tricyclic antidepressants, glucocorticoids, gabapentin, pregabalin) 3
• Prescribing without follow-up plan: Close monitoring every 4-6 weeks enables support for lifestyle changes and early detection of adverse effects 6