What are all the weight loss medications available?

Weight Loss Medications Available

The FDA has approved six medications for long-term weight management: semaglutide, liraglutide, tirzepatide, phentermine-topiramate, naltrexone-bupropion, and orlistat, with tirzepatide demonstrating the greatest efficacy at 21% mean weight loss at 72 weeks. 1

First-Line Long-Term Medications

GLP-1 Receptor Agonists (Most Effective)

• Semaglutide (Wegovy brand for obesity): Achieves 8-21% weight reduction and should be prioritized as first-line therapy due to superior efficacy and cardiovascular benefits 1
• Liraglutide (Saxenda brand for obesity): Produces 8-21% weight loss with proven cardiovascular safety 1, 2
• Tirzepatide (Zepbound brand for obesity): Dual GIP/GLP-1 agonist producing the highest weight loss of 21% at 72 weeks, making it the most effective FDA-approved option 1

Combination Medications

• Phentermine-topiramate extended release: Produces clinically meaningful weight loss, approved for BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities 1, 3
• Naltrexone-bupropion: Achieves approximately 4.8% weight loss at 56 weeks 1, 2

Lipase Inhibitor

• Orlistat: Reduces fat absorption, achieving modest weight loss of approximately 2.9 kg at 12 months with the added benefit of LDL cholesterol reduction beyond weight loss alone 1, 2

Short-Term Medications (FDA-Approved for 12 Weeks)

Sympathomimetic Amines

• Phentermine: Most commonly prescribed short-term agent, affordable alternative producing 3.75% weight loss, but avoid in coronary artery disease, uncontrolled hypertension, glaucoma, and substance use disorder history 1, 4
• Diethylpropion: Schedule IV controlled substance with low abuse risk 1
• Benzphetamine: Noradrenergic appetite suppressant 1
• Phendimetrazine: Increases norepinephrine for appetite suppression 1

Off-Label Medications Commonly Used

Diabetes Medications Used for Weight Loss

• Metformin: Produces approximately 3% weight loss, with doses >1500 mg showing greatest efficacy; 6.2% weight loss maintained at 15-year follow-up in the Diabetes Prevention Program 1
• SGLT-2 inhibitors: Produce clinically meaningful weight loss with added cardiometabolic benefits 1

Brand Names Approved Only for Diabetes (Not Obesity)

• Ozempic (semaglutide injection for diabetes): Insurance may restrict coverage to diabetes indication only 1
• Mounjaro (tirzepatide injection for diabetes): Insurance may restrict coverage to diabetes indication only 1
• Victoza (liraglutide injection for diabetes): Lower dose than Saxenda 1
• Rybelsus (oral semaglutide for diabetes): Oral formulation 1

Medications to Avoid

Withdrawn or Contraindicated

• Sibutramine: Should be avoided due to cardiac effects and contribution to heart failure development 1
• Ephedra preparations: May contribute to heart failure development and should be avoided 1
• Fenfluramine and dexfenfluramine: Withdrawn due to cardiac valve effects 1

Special Population Considerations

Children and Adolescents

• Orlistat: Only FDA-approved weight loss medication for children ≥12 years old, showing modest efficacy 1
• All adult medications are approved for children ≥16 years old 5
• Studies of newer agents (phentermine-topiramate, lorcaserin, naltrexone-bupropion, liraglutide) in adolescents are anticipated 1

Patients with Diabetes

• Prioritize GLP-1 agonists or tirzepatide (semaglutide or tirzepatide specifically) due to glycemic benefits and weight-independent cardiometabolic advantages 1
• Avoid insulin secretagogues, thiazolidinediones, and insulin when possible as they cause weight gain 1

Patients with Heart Failure

• Orlistat is the only medication studied in heart failure patients, showing 4.65 kg weight loss at 12 weeks with improved 6-minute walk distance 1
• Avoid sibutramine and ephedra preparations entirely 1
• Lorcaserin safety is unknown in heart failure; FDA mandated postmarketing cardiovascular studies 1

Experimental Medications in Development

Triple Agonist

• Retatrutide: Experimental GLP-1/GIP/glucagon triple agonist showing 15-25% weight reduction in trials, approaching bariatric surgery results 6
• Initial dosing suggested at 2 mg subcutaneous weekly, titrating to 12 mg weekly 6

Critical Implementation Points

Efficacy Hierarchy

For maximum weight loss, prescribe in this order: tirzepatide (21%) > semaglutide (15-17%) > liraglutide (8-10%) > phentermine-topiramate > naltrexone-bupropion (4.8%) > orlistat (2.9 kg). 1, 2, 4

Common Pitfalls

• Medicare excludes coverage of FDA-approved obesity medications for obesity diagnosis alone 1
• Global shortages currently exist, especially for GLP-1 receptor agonists 1
• All medications require continuation for sustained benefit; weight regain occurs with discontinuation 1
• Medications must be combined with lifestyle modifications (reduced-calorie diet and physical activity) for FDA-approved indications 1

Monitoring Requirements

• Assess efficacy and safety monthly for first 3 months, then every 3 months 2
• If not achieving goals, intensify treatment rather than accepting therapeutic inertia 1
• Contraception counseling required for individuals of childbearing potential due to teratogenic risks 1