What are the available medication options for weight loss?

Weight Loss Medication Options

For patients seeking pharmacologic weight loss therapy, GLP-1 receptor agonists (semaglutide, liraglutide) should be considered first-line due to superior weight reduction (8-21%) and cardiovascular benefits, followed by orlistat as an alternative first-line option for patients without cardiovascular disease. 1

FDA-Approved Medications for Chronic Weight Management

GLP-1 Receptor Agonists (Preferred First-Line)

• Liraglutide (Saxenda) and semaglutide provide the most substantial weight loss (8-21% body weight reduction) and offer additional cardiovascular benefits and improvements in hepatic steatosis 1
• These agents work as gut-derived incretin hormone analogues with 97% homology to human GLP-1 2
• Particularly beneficial for patients with multiple comorbidities including fatty liver disease, hyperlipidemia, and metabolic syndrome 1

Orlistat (Alternative First-Line)

• Orlistat 120 mg three times daily with meals is recommended as first-line therapy when combined with a hypocaloric diet (30% calories from fat) and daily multivitamin 3
• Blocks approximately 30% of ingested fat absorption by inhibiting pancreatic and gastric lipases 2
• Produces 2.59-2.89 kg weight loss at 6-12 months 2
• Available over-the-counter as Alli (60 mg) at half the prescription dose 2
• Key advantage: Particularly useful for patients with obesity and constipation 2
• Critical requirement: Patients must take a multivitamin supplement because orlistat decreases absorption of fat-soluble vitamins (A, D, E, K) 2

Phentermine/Topiramate Extended-Release (Qsymia)

• Provides 7.8-9.8% weight loss at one year through dual mechanism: sympathetic activation (phentermine) plus appetite suppression and increased satiation (topiramate) 2, 3
• Dosing algorithm: Start 3.75/23 mg daily for 14 days, then 7.5/46 mg daily; at 12 weeks escalate to 11.25/69 mg then 15/96 mg if needed 2
• Discontinuation criteria: Stop if <3% weight loss after 12 weeks at 7.5/46 mg dose, or if <5% weight loss after 12 weeks at 15/92 mg dose 2
• Contraindication: Not recommended for patients with cardiovascular disease 3

Bupropion/Naltrexone Sustained-Release (Contrave)

• Achieves approximately 4.8% weight loss at 56 weeks through synergistic activation of POMC neurons 2, 1
• Dosing: Start 1 tablet (8 mg naltrexone/90 mg bupropion) daily, increase by 1 tablet weekly to maximum 2 tablets twice daily (32/360 mg total) 2
• Discontinuation criteria: Stop if <5% weight loss at 12 weeks 2
• Consider as alternative if GLP-1 agonists or other options unsuitable 1

Lorcaserin (Belviq) - Note: Withdrawn from Market

• Previously approved in 2012 as selective 5-HT2C receptor agonist 2
• Dosed at 10 mg twice daily with discontinuation if <5% weight loss after 12 weeks 2

Short-Term Monotherapy Option

Phentermine (Monotherapy)

• FDA-approved only for short-term use (few weeks), though many providers prescribe off-label for longer duration 2, 4
• Produces 6.0 kg weight loss at 28 weeks; 46% achieve ≥5% weight loss, 20.8% achieve ≥10% weight loss 2
• Dosing: 15-37.5 mg orally once daily in morning, or low-dose 8 mg up to three times daily (Lomaira) 2, 4
• Appropriate candidates: Younger patients needing appetite suppression without active/unstable coronary disease or uncontrolled hypertension 2
• Avoid in: Patients with cardiovascular disease, uncontrolled hypertension, anxiety, insomnia, or within 14 days of MAOIs 2, 4
• Common side effects include dry mouth, insomnia, dizziness, and irritability 2

Treatment Algorithm

Step 1: Patient Selection

• Confirm BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities (hypertension, diabetes, hyperlipidemia) 3, 4
• Evaluate cardiovascular risk factors and lipid profile before initiating therapy 3

Step 2: Medication Selection

• First choice: GLP-1 receptor agonists for patients with multiple comorbidities or cardiovascular disease 1
• Alternative first choice: Orlistat 120 mg three times daily for patients preferring non-injectable therapy or with constipation 2, 3
• Second-line: Phentermine/topiramate ER for patients without cardiovascular disease needing more aggressive therapy 3
• Third-line: Bupropion/naltrexone SR if other options unsuitable 1
• Short-term only: Phentermine monotherapy for brief appetite suppression in appropriate candidates 2, 4

Step 3: Monitoring and Continuation Criteria

• Assess weight loss at 12 weeks 2, 3
• Continue therapy only if: ≥5% weight loss achieved (some medications require ≥3% at lower doses) 2, 3
• Monitor at least monthly for first 3 months, then every 3 months 1
• Track liver enzymes, lipid profile, and comorbidity symptoms 1

Critical Considerations

Realistic Expectations

• Set expectation for 5-10% body weight loss with medication therapy—the primary goal is improving comorbid conditions (hyperglycemia, hyperlipidemia, cardiovascular disease) rather than dramatic weight reduction 2, 3
• All medications must be combined with lifestyle modifications including diet, exercise, and behavioral changes 3

Important Warnings

• Never combine phentermine with other weight loss drugs including over-the-counter preparations, herbal products, or serotonergic agents (SSRIs)—safety and efficacy of combination therapy not established 4
• Rapid weight loss (>1.6 kg/week) may worsen portal inflammation and fibrosis in patients with fatty liver disease 1
• Sympathomimetic agents like phentermine should be avoided in patients with cardiovascular disease 1
• All weight loss medications have limited long-term safety data beyond 1-2 years 2, 4

Dietary Requirements

• Mediterranean diet emphasizing vegetables, fruits, whole grains, nuts, fish, olive oil with minimal simple sugars and red meats 1
• For orlistat: approximately 30% of calories from fat to minimize gastrointestinal side effects 2
• Progressive weight loss <1 kg/week recommended to avoid worsening liver inflammation 1

Exercise Requirements

• 150-300 minutes of moderate-intensity exercise per week provides benefits even without significant weight loss 1