What medications are recommended for a patient seeking weight loss management?

Medications for Weight Loss Management

For most patients seeking weight loss, start with semaglutide 2.4 mg weekly as first-line pharmacotherapy combined with lifestyle modification, as it produces the greatest weight loss (approximately 15% at one year) with established cardiovascular benefits. 1, 2

Patient Eligibility Criteria

Pharmacotherapy should be considered for patients meeting these thresholds 1:

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

First-Line Medication Options

GLP-1 Receptor Agonists (Preferred)

Semaglutide 2.4 mg (Wegovy) 1, 2:

• Dosing: Start 0.25 mg subcutaneously weekly, escalate by 0.25-0.5 mg every 4 weeks to target 2.4 mg weekly 3
• Expected weight loss: 14.9% at 68 weeks; 15% at 1 year 3, 2
• Side effects: Nausea, hypoglycemia (in diabetics), diarrhea, constipation, vomiting, headache 1
• Monitoring: Watch for pancreatitis and gallbladder disease 3

Liraglutide 3.0 mg (Saxenda) 1, 3:

• Dosing: Start 0.6 mg daily subcutaneously, escalate by 0.6 mg weekly up to 3.0 mg daily 1
• Expected weight loss: 5.4% at 56 weeks; 8.0% at 12 months 1, 3
• Side effects: Similar to semaglutide but generally better tolerated 3

Second-Line Medication Options

Phentermine/Topiramate ER (Qsymia)

Use when GLP-1 agonists are contraindicated or not tolerated 1, 4:

• Dosing: Start 3.75 mg/23 mg daily, escalate gradually (7.5/46 mg, then 11.25/69 mg, then 15/92 mg) 1, 4
• Expected weight loss: 6.6% at 1 year; 9.8% at 52 weeks 1, 3
• Critical contraindications: Uncontrolled hypertension, cardiovascular disease, hyperthyroidism, glaucoma, pregnancy 4
• Mandatory: Effective contraception in women of childbearing potential due to teratogenic effects 4, 3
• Monitoring: Baseline and periodic electrolytes, creatinine, blood pressure, heart rate; watch for cognitive impairment, mood changes, suicidal ideation, metabolic acidosis 4

Naltrexone SR/Bupropion SR (Contrave)

Alternative when sympathomimetics are contraindicated 1, 4:

• Dosing: Start 8 mg/90 mg once daily in morning, escalate to 16 mg/180 mg twice daily over 4 weeks 1, 4
• Expected weight loss: 4.8% at 56 weeks; 5-6.1% total body weight 1, 4
• Contraindications: Uncontrolled hypertension, seizure history, eating disorders, opioid dependence, abrupt alcohol/benzodiazepine discontinuation 4
• Monitoring: Blood pressure, heart rate; watch for seizures, neuropsychiatric symptoms, hepatotoxicity 4

Third-Line Options

Orlistat (Xenical/Alli)

Reserved for patients who cannot tolerate other medications 1:

• Dosing: 120 mg three times daily with meals 1, 5
• Expected weight loss: 2.89 kg at 12 months; 3.1% at 1 year 1
• Side effects: Oily spotting, fecal urgency, fatty stools, fecal incontinence 1
• Avoid in: Patients with colostomy due to severe GI effects and malabsorption 4
• Required: Daily multivitamin at bedtime due to fat-soluble vitamin malabsorption 5

Phentermine (Adipex)

Short-term use only (few weeks) for rapid appetite suppression 1:

• Dosing: 15-37.5 mg once daily in morning 1
• Expected weight loss: 3.6 kg; 5.1% at 28 weeks 1
• Avoid in: Patients with cardiovascular disease, uncontrolled hypertension, anxiety, insomnia 1, 3
• Not approved for long-term use 1

Special Population Considerations

Patients with Type 2 Diabetes

Prioritize GLP-1 agonists (semaglutide or liraglutide) as they provide dual benefits of glycemic control and weight loss 1:

• Consider metformin as first-line antidiabetic (weight neutral to modest loss) 1
• Avoid or minimize insulin, sulfonylureas, thiazolidinediones (associated with weight gain) 1
• Consider SGLT2 inhibitors (weight loss benefit) 1

Patients with Cardiovascular Disease

Avoid sympathomimetic agents (phentermine, phentermine/topiramate ER) 1, 3:

• Safer alternatives: Lorcaserin (if available), orlistat, GLP-1 agonists 1
• Semaglutide has cardiovascular outcome trial (SELECT) showing benefits 2

Critical Implementation Requirements

Mandatory Lifestyle Modification

All pharmacotherapy MUST be combined with 1, 4:

• Diet: 500-750 kcal/day deficit from baseline 3
• Exercise: 150-300 minutes/week moderate-intensity aerobic activity plus resistance training 2-3 times weekly 3
• Behavioral counseling: Structured weight management program with self-monitoring 4, 3

Discontinuation Criteria

Stop medication if 1, 4:

• <5% weight loss after 3 months at therapeutic dose 1
• <4% weight loss after 16 weeks for liraglutide 3
• Any safety or tolerability issues at any time 1

Monitoring Schedule

Assess efficacy and safety 1:

• Monthly for first 3 months 1
• Every 3 months thereafter 1

Common Pitfalls to Avoid

Never combine bupropion with topiramate as separate agents - this creates dangerous drug interactions including increased seizure risk and cognitive impairment; use FDA-approved fixed-dose combinations only 4

Never prescribe topiramate-containing products without contraception counseling in women of childbearing potential due to teratogenic effects 4, 3

Never use anti-obesity medications during pregnancy 3

Never prescribe medication alone without intensive lifestyle intervention - medications are adjuncts, not standalone therapy 1, 6

Review and minimize medications causing weight gain (antipsychotics, certain antidepressants, insulin, corticosteroids) before adding anti-obesity medication 1