What are the recommended medications for weight loss?

Recommended Medications for Weight Loss

For patients with BMI ≥30 kg/m² or BMI ≥27 kg/m² with weight-related comorbidities, GLP-1 receptor agonists (semaglutide 2.4 mg or liraglutide 3.0 mg) are the most effective first-line pharmacotherapy options, producing 8-21% weight reduction compared to 3-5% with older agents. 1, 2

Patient Selection Criteria

Pharmacotherapy should be considered for: 3, 4

• BMI ≥30 kg/m² (obesity) regardless of comorbidities
• BMI ≥27 kg/m² with at least one weight-related comorbidity (hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea)
• Patients who have failed adequate diet and exercise programs alone

Critical caveat: Weight loss medications should NOT be prescribed to patients with normal BMI, as the risk-benefit ratio is unfavorable. 4

FDA-Approved Long-Term Medications (Ranked by Efficacy)

First-Line: GLP-1 Receptor Agonists

Semaglutide 2.4 mg (Wegovy) - Most effective option 2, 5

• Mechanism: GLP-1 receptor agonist
• Dosing: Weekly subcutaneous injection, escalated from 0.25 mg to 2.4 mg over 16-20 weeks
• Weight loss: ~15% at 1 year 2
• Additional benefits: Improves hepatic steatosis, metabolic parameters 1
• Side effects: Nausea, diarrhea, constipation, vomiting, abdominal pain 3

Liraglutide 3.0 mg (Saxenda) 3, 1, 5

• Mechanism: GLP-1 receptor agonist
• Dosing: Daily subcutaneous injection, escalated by 0.6 mg weekly to 3.0 mg
• Weight loss: 5.4% at 56 weeks (8-21% range) 3, 1
• Side effects: Nausea, hypoglycemia, diarrhea, constipation, headache 3

Second-Line: Combination Agents

Phentermine/Topiramate ER (Qsymia) 3, 5

• Mechanism: Adrenergic agonist/neurostabilizer
• Dosing: Start 3.75/23 mg daily, escalate to 15/92 mg daily
• Weight loss: 6.6% at 1 year 3
• Contraindications: Cardiovascular disease, pregnancy (teratogenic), glaucoma 3, 6
• Side effects: Paresthesia, dizziness, dysgeusia, insomnia, constipation 3

Naltrexone SR/Bupropion SR (Contrave) 3, 1, 5

• Mechanism: Opioid antagonist/dopamine-norepinephrine reuptake inhibitor
• Dosing: Escalate to 16/180 mg twice daily
• Weight loss: 4.8% at 56 weeks 3, 1
• Side effects: Nausea, constipation, headache, dizziness 3
• Warning: Seizure risk, blood pressure elevation 4

Third-Line: Lipase Inhibitor

Orlistat (Xenical 120 mg, Alli 60 mg OTC) 3

• Mechanism: Inhibits gastrointestinal lipases, reduces fat absorption by 30%
• Dosing: 120 mg three times daily with meals
• Weight loss: 2.9-3.1 kg at 1 year 3, 1
• Side effects: Oily spotting, fecal urgency, flatulence, fat-soluble vitamin deficiencies 3, 4
• Advantage: Safer in cardiovascular disease 3

Short-Term Only: Sympathomimetics

Phentermine (Adipex, Lomaira) 3, 6

• Mechanism: Adrenergic agonist (appetite suppressant)
• Dosing: 15-37.5 mg once daily in morning, or 8 mg three times daily
• Weight loss: 3.6-5.1 kg at 28 weeks 3
• FDA-approved for short-term use only (few weeks) 6
• Contraindications: Cardiovascular disease, uncontrolled hypertension, hyperthyroidism, glaucoma, history of drug abuse 3, 6
• Side effects: Elevated blood pressure/heart rate, insomnia, dry mouth, anxiety 3

Special Population Considerations

Patients with Type 2 Diabetes 3, 1

• Prioritize GLP-1 agonists (semaglutide or liraglutide) for dual glycemic control and weight loss
• Consider metformin as first-line antidiabetic (weight neutral to modest loss)
• Avoid or minimize: insulin, sulfonylureas, thiazolidinediones (all cause weight gain) 3

Patients with Cardiovascular Disease 3, 1

• Avoid sympathomimetics (phentermine, phentermine/topiramate)
• Safer alternatives: Lorcaserin (no longer available in US), orlistat, GLP-1 agonists 3

Patients with Fatty Liver Disease 1

• GLP-1 agonists preferred - reduce hepatic steatosis
• Target 5-7% weight loss to decrease intrahepatic fat; >10% improves fibrosis in 45% 1
• Avoid rapid weight loss (>1 kg/week) - may worsen portal inflammation 1

Patients with Renal Impairment 6

• Phentermine: Maximum 15 mg daily if eGFR 15-29 mL/min/1.73m²
• Avoid if eGFR <15 mL/min or dialysis-dependent 6

Treatment Algorithm

1. Initiate lifestyle modifications (diet, 150-300 min/week moderate exercise) in ALL patients 1

2. Add pharmacotherapy if BMI criteria met and lifestyle changes insufficient 3

3. First choice: GLP-1 agonist (semaglutide or liraglutide) unless contraindicated 1, 2

4. Alternative if GLP-1 not suitable: Phentermine/topiramate (if no CVD/pregnancy risk) or naltrexone/bupropion 3

5. If CVD present: Orlistat or GLP-1 agonist 3

6. Assess response at 3 months: If <5% weight loss, discontinue and try alternative medication 3

7. Continue monitoring: Monthly for first 3 months, then every 3 months 3, 1

Critical Monitoring and Discontinuation Criteria

Discontinue medication if: 3

• <5% weight loss after 3 months of treatment
• Intolerable side effects at any time
• Development of contraindications

Common pitfall: Medications must be combined with intensive lifestyle programs - they are adjuncts, not standalone therapy. 3, 6

Long-term use: All FDA-approved long-term agents (except phentermine) should be prescribed with intention of chronic use, as obesity is a chronic disease and weight regain occurs upon discontinuation. 4, 5

Emerging Therapies

Tirzepatide (dual GLP-1/GIP agonist) shows even greater efficacy than semaglutide in phase 3 trials and is FDA-approved for obesity. 2, 5