What are the FDA-approved medications for weight loss?

FDA-Approved Weight Loss Medications

For most patients seeking long-term weight management, semaglutide 2.4 mg weekly or tirzepatide should be the first-line choice due to superior efficacy (15-21% weight loss) and cardiovascular benefits, with five other FDA-approved medications available for chronic use: orlistat, phentermine/topiramate ER, naltrexone/bupropion ER, liraglutide 3.0 mg, and phentermine (short-term only). 1

Indications for Pharmacotherapy

Prescribe weight loss medications for patients with:

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

FDA-Approved Medications for Long-Term Use (>12 weeks)

First-Line: GLP-1 Receptor Agonists

Semaglutide 2.4 mg (Wegovy) and tirzepatide are preferred first-line agents for most patients due to superior efficacy and cardiovascular benefits. 1

Liraglutide 3.0 mg (Saxenda):

• Mean weight loss: 5.4% at 56 weeks 1
• Requires dose escalation: start 0.6 mg daily, increase by 0.6 mg weekly up to 3.0 mg 1
• Mechanism: GLP-1 receptor agonist that reduces appetite and slows gastric emptying 3
• Common side effects: nausea, constipation, dizziness, headache 2
• Contraindications: pregnancy, personal/family history of medullary thyroid carcinoma or MEN2 2

Second-Line Options

Phentermine/Topiramate ER (Qsymia):

• Mean weight loss: 6.6-9.8% at 1 year 2, 1
• Fixed-dose combination targeting multiple pathways (sympathomimetic + GABA modulation) 2
• Dosing: start low and titrate; maintenance dose typically 7.5 mg/46 mg daily 2
• Common side effects: constipation, paresthesia, insomnia, dry mouth 2
• Major contraindications: cardiovascular disease, pregnancy, glaucoma, hyperthyroidism, recent MAOI use 2, 1
• Requires monthly pregnancy testing for women of reproductive age 1

Naltrexone/Bupropion ER (Contrave):

• Mean weight loss: 4.0% at 1 year 4
• Combination targets appetite control through opioid and dopamine/norepinephrine pathways 2
• Common side effects: nausea, constipation, headache, dizziness 2
• Contraindications: pregnancy, uncontrolled hypertension, seizure history, eating disorders, opioid use, recent MAOI use 2

Orlistat (Xenical 120 mg/Alli 60 mg OTC):

• Mean weight loss: 2.9-3.1% at 1 year 2, 1
• Mechanism: blocks ~30% of dietary fat absorption via pancreatic/gastric lipase inhibition 2, 1
• Dosing: 120 mg three times daily with meals containing fat 2
• Requires daily multivitamin supplementation (fat-soluble vitamins A, D, E, K) taken 2+ hours apart from orlistat 2, 1
• Common side effects: abdominal pain, flatulence, fecal urgency, oily stools 2
• Best for: patients with obesity and constipation, cardiovascular contraindications to sympathomimetics, or limited financial resources 1
• Contraindications: chronic malabsorption syndrome, cholestasis 2
• Drug interactions: cyclosporine, L-thyroxine, warfarin, antiepileptics 2

Short-Term Only (≤12 weeks FDA-approved)

Phentermine monotherapy:

• FDA-approved for short-term use (3 months) only 2, 5
• Mean weight loss: 6.0-6.1% at 28 weeks; 46% achieve ≥5% weight loss 1
• Commonly prescribed off-label for longer durations in clinical practice 2
• Dosing: 15-37.5 mg once daily, typically 2 hours after breakfast; individualize to lowest effective dose 2, 5
• Mechanism: sympathomimetic amine that increases norepinephrine, raising energy expenditure and suppressing appetite 2
• Common side effects: dry mouth, insomnia, dizziness, irritability 2, 5
• Monitor blood pressure and heart rate regularly 1
• Major contraindications: cardiovascular disease (coronary artery disease, stroke, arrhythmias, CHF, uncontrolled hypertension), hyperthyroidism, glaucoma, agitated states, drug abuse history, pregnancy, recent MAOI use 5
• Renal dosing: maximum 15 mg daily for eGFR 15-29; avoid if eGFR <15 or dialysis 5
• FDA warnings: risk of primary pulmonary hypertension and valvular heart disease (rare but serious); abuse potential similar to amphetamines 5

Clinical Decision Algorithm

Step 1: Assess for contraindications

• Cardiovascular disease → avoid phentermine and phentermine/topiramate; consider orlistat or GLP-1 agonists 1, 5
• Pregnancy/nursing → all weight loss medications contraindicated 2
• Glaucoma/hyperthyroidism → avoid sympathomimetics (phentermine, phentermine/topiramate) 2, 5

Step 2: Select first-line agent

• Most patients: semaglutide 2.4 mg or tirzepatide (superior efficacy, CV benefits) 1
• If GLP-1 contraindicated/unavailable: phentermine/topiramate ER 1
• Constipation present: orlistat 1
• Limited budget: orlistat (available OTC) 1
• Short-term need only: phentermine monotherapy 2, 5

Step 3: Initiate and monitor

• Assess monthly for first 3 months, then quarterly 1
• Discontinue or switch if <5% weight loss after 3 months at therapeutic dose 2, 1
• Continue medication beyond weight loss goals to maintain benefits—obesity is a chronic disease requiring indefinite treatment 1

Critical Monitoring and Safety Considerations

Efficacy assessment:

• Early response (>5% weight loss at 3 months) predicts continued success 2
• If insufficient response (<5% at 3 months), discontinue and try alternative medication 2, 1

Medication-specific monitoring:

• Phentermine: blood pressure, heart rate, signs of pulmonary hypertension (dyspnea, angina, syncope, edema) 1, 5
• Orlistat: fat-soluble vitamin levels, ensure multivitamin compliance 2, 1
• Phentermine/topiramate: monthly pregnancy testing for women of reproductive age 1

Common Pitfalls to Avoid

• Never combine phentermine with other weight loss medications—safety not established and increases cardiovascular risk 1, 5
• Never exceed recommended phentermine doses when tolerance develops—discontinue instead 5
• Avoid β-blockers as antihypertensives in obese patients—they promote weight gain 1
• Do not use phentermine monotherapy beyond short-term without acknowledging off-label status 2, 5
• Ensure contraception counseling for all women of reproductive potential on weight loss medications 2