What are the available weight loss medications, including over-the-counter (OTC) and prescription options like Orlistat (Xenical), phentermine-topiramate (Qsymia), liraglutide (Victoza), and semaglutide (Wegovy)?

Available Weight Loss Medications

For patients with obesity (BMI ≥30 kg/m²) or overweight with complications (BMI ≥27 kg/m²), tirzepatide is the most effective FDA-approved option producing 21% weight loss, followed by semaglutide achieving 15-17% weight loss, both superior to older agents and recommended as first-line therapy when combined with lifestyle modification. 1

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

GLP-1 and Dual Agonists (Most Effective)

Tirzepatide (dual GIP/GLP-1 agonist)

• Produces 21% weight loss at 72 weeks, making it the most effective FDA-approved option 1
• Particularly beneficial for patients with type 2 diabetes due to glycemic benefits and weight-independent cardiometabolic advantages 1
• Mechanism: centrally reduces appetite, increases satiety, and slows gastric emptying 2

Semaglutide 2.4 mg (Wegovy)

• Achieves 15-17% weight loss at 1 year, substantially more effective than older medications 1, 3
• Recommended by the American Heart Association as first-line therapy with proven cardiovascular benefits 1
• Available as weekly subcutaneous injection 3
• Currently approved in the United States and Europe but not yet in all Asian countries 4

Liraglutide 3.0 mg (Saxenda)

• Produces 8-10% weight loss with proven cardiovascular safety 1
• Recommended by the American Diabetes Association as an alternative first-line option 1
• Particularly useful in post-bariatric surgery patients requiring better diabetes control 4
• Daily subcutaneous injection with dose escalation from 0.6 mg to 3.0 mg over 5 weeks 4
• Approved for adolescents ≥12 years old in select countries 4
• Common side effects: nausea, hypoglycemia, diarrhea, constipation, vomiting, headache 4

Combination Medications (Moderate Efficacy)

Phentermine/Topiramate Extended-Release (Qsymia)

• Produces 6.6% weight loss at 1 year, clinically meaningful reduction 4, 1
• Approved for BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 1
• Dose escalation: start 3.75/23 mg daily, increase to maximum 15/92 mg daily 4
• Critical contraindication: avoid in patients with cardiovascular disease due to sympathomimetic effects 4
• Other contraindications: pregnancy (teratogenic), glaucoma, hyperthyroidism, MAOI use within 14 days 4
• Common side effects: paresthesia, dizziness, altered taste, insomnia, constipation 4
• Schedule IV controlled substance 4

Naltrexone ER/Bupropion ER (Contrave)

• Achieves 4.8% weight loss at 56 weeks 4, 1
• Recommended by the American College of Cardiology as an option for appropriate patients 1
• Dose escalation to 16/180 mg twice daily 4
• Contraindications: uncontrolled hypertension, seizure disorders, eating disorders, opioid use, MAOI use within 14 days 4
• Common side effects: nausea, constipation, dizziness, insomnia, dry mouth 4
• Available in Singapore; limited availability in South/Southeast Asia 4

Lipase Inhibitor (Modest Efficacy)

Orlistat (Xenical)

• Produces modest weight loss of 2.9 kg (approximately 3.1%) at 12 months 4, 1
• Recommended by the American Gastroenterological Association with added benefit of LDL cholesterol reduction beyond weight loss alone 1
• Safest option for patients with cardiovascular disease, heart failure, or renal disease 1, 5
• Only medication widely available across South and Southeast Asia 4
• Only FDA-approved weight loss medication for children ≥12 years old 1
• Dosing: 120 mg three times daily with each fat-containing meal 4, 5
• Mechanism: blocks approximately 30% of dietary fat absorption without systemic effects 5
• Common side effects: oily spotting, fecal urgency, fatty stools, increased defecation, fecal incontinence 4
• Must prescribe daily multivitamin to prevent fat-soluble vitamin deficiencies 5
• Contraindications: chronic malabsorption syndrome, cholestasis 5
• Drug interactions: cyclosporine, levothyroxine, warfarin, antiepileptic drugs 5

Short-Term Medications (≤12 Weeks)

Phentermine (Adipex)

• Produces 3.75-5.1% weight loss at 28 weeks 4, 1
• Most commonly prescribed anti-obesity medication historically in the United States 4
• Dosing: 15 mg daily (can use quarter or half tablet) 4
• Avoid in coronary artery disease, uncontrolled hypertension, glaucoma, substance use disorder history 1
• Contraindications: cardiovascular disease, hyperthyroidism, agitated states, MAOI use within 14 days 4
• Common side effects: dizziness, dry mouth, insomnia, irritability, nausea 4
• Schedule IV controlled substance 4
• Approved for short-term use only in Malaysia, Philippines, Singapore, Thailand 4

Off-Label Medications with Weight Loss Benefits

Metformin

• Produces approximately 3% weight loss, with doses >1500 mg showing greatest efficacy 1
• Recommended by the American Diabetes Association for patients with diabetes 1
• First-line agent for type 2 diabetes with weight loss as additional benefit 4

SGLT-2 Inhibitors

• Produce clinically meaningful weight loss with added cardiometabolic benefits 1
• Recommended by the Endocrine Society as an option 1
• Beneficial for patients with type 2 diabetes requiring glucose-lowering agents that promote weight loss 4

Indications for Pharmacotherapy

Standard BMI Criteria

• BMI ≥30 kg/m² (obesity) 4, 1
• BMI ≥27 kg/m² with weight-related comorbidities (hypertension, type 2 diabetes, dyslipidemia, obstructive sleep apnea) 4, 1

Modified Criteria for Asian Populations

• BMI >27 kg/m² or >25 kg/m² with complications for Asian Indian adults 4
• Waist circumference at least 10 cm greater than upper limit of normal for Asian men and women 4
• Lower thresholds reflect that Asian populations experience obesity-related complications at lower BMIs 4

Additional Considerations

• Patients who have failed to achieve weight loss with diet and exercise alone 4, 1
• Patients whose clinical circumstances require expedited weight loss 4
• Medications should never be used alone but always combined with intensive lifestyle program 4

Treatment Algorithm by Clinical Scenario

For Maximum Weight Loss (No Contraindications)

• First choice: Tirzepatide (21% weight loss) 1
• Second choice: Semaglutide 2.4 mg (15-17% weight loss) 1
• Third choice: Liraglutide 3.0 mg (8-10% weight loss) 1

For Patients with Type 2 Diabetes

• Prioritize GLP-1 agonists (tirzepatide, semaglutide, liraglutide) for glycemic benefits and weight-independent cardiometabolic advantages 1
• Consider SGLT-2 inhibitors or metformin as alternatives 1

For Patients with Cardiovascular Disease

• Avoid sympathomimetic agents (phentermine, phentermine/topiramate) 4
• Safer alternatives: liraglutide (proven CV safety), orlistat 4

For Patients with Heart Failure

• Orlistat is the only medication studied in this population, showing 4.65 kg weight loss at 12 weeks with improved 6-minute walk distance 1

For Patients with Renal Disease

• Orlistat is safest due to local gastrointestinal mechanism without systemic absorption 5
• Avoid sympathomimetic agents due to effects on blood pressure and fluid retention 5
• GLP-1 agonists may be considered only after disease remission with normal renal function 5

For Post-Bariatric Surgery Patients

• Liraglutide is best studied and similarly efficacious in this population 4
• Particularly useful for patients requiring better diabetes control 4
• Extended pharmacotherapy may be needed as weight regain is common (mean 14% of nadir weight by 5 years) 4

For Adolescents ≥12 Years Old

• Orlistat is the only FDA-approved option showing modest efficacy 1
• Liraglutide 3.0 mg approved in select countries (Singapore, Thailand, Philippines) 4

Monitoring and Discontinuation Criteria

Initial Assessment

• Assess efficacy and safety monthly for first 3 months, then at least every 3 months 4
• Weight loss and tolerability should be monitored 5

Discontinuation Criteria

• Stop medication if weight loss is <5% of total body weight after 12 weeks on maximally tolerated dosage 4
• This is required by terms of authorization 4

Long-Term Considerations

• Extended treatment may be needed to support weight maintenance and provide long-term health benefits 4
• Weight regain is common when medication is withdrawn 4
• All medications require continuation for sustained benefit; weight regain occurs with discontinuation 1
• Long-term improvement in obesity-related complications has not been demonstrated with short-term pharmacotherapy 4

Regional Availability (South/Southeast Asia)

Widely Available

• Orlistat: available in all countries (Bangladesh, Brunei, India, Indonesia, Malaysia, Philippines, Singapore, Sri Lanka, Thailand, Vietnam) 4

Moderately Available

• Liraglutide 3.0 mg: available in most countries except India 4
• Phentermine: available in Malaysia, Philippines, Singapore, Thailand (short-term use only) 4

Limited Availability

• Naltrexone ER/Bupropion ER: only Singapore 4
• Phentermine/Topiramate: not currently approved in South/Southeast Asia but approved in other parts of Asia 4
• Semaglutide 2.4 mg: not yet approved for obesity in Asia (approved for diabetes) 4

Critical Pitfalls to Avoid

Inappropriate Prescribing

• Never prescribe weight loss medications to patients with normal BMI (BMI <25 kg/m²) 6
• Do not prescribe based solely on patient request without appropriate BMI criteria 6
• Do not use medications alone without intensive lifestyle program 4

Cardiovascular Risks

• Never use sympathomimetic agents (phentermine, phentermine/topiramate) in patients with cardiovascular disease, uncontrolled hypertension, or unstable cardiovascular status 4, 5

Medication-Specific Concerns

• Phentermine/topiramate is teratogenic; ensure adequate contraception 4
• Orlistat requires fat-soluble vitamin supplementation 5
• GLP-1 agonists cause significant gastrointestinal side effects that may exacerbate nutritional deficiencies in vulnerable populations 5

Unrealistic Expectations

• Weight loss from medications is typically temporary without continued use 6
• Individual aspirational weight goals may be more ambitious than clinical targets; weight stabilization at lower baseline should be regarded as success 4
• Improvements in obesity-related complications and quality of life may persist despite some weight regain 4