There are several FDA-approved prescription medications for long-term weight management, and they differ a lot in how they work and how much weight loss they produce. Here is a clear comparison of the main options.
Quick answer
The FDA-approved prescription weight-loss drugs for long-term use are orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound). The GLP-1-class drugs, semaglutide and tirzepatide, produce the largest average weight loss, with tirzepatide leading semaglutide in head-to-head data. Older options like orlistat, Qsymia, and Contrave generally produce less weight loss but offer different mechanisms and price points. The best choice depends on your health, tolerance, and cost.
The main FDA-approved weight-loss drugs
Each works through a different mechanism.
- Orlistat (Xenical, Alli): Blocks absorption of some dietary fat in the gut. Modest weight loss; can cause GI side effects. Alli is available over the counter at a lower dose.
- Phentermine-topiramate (Qsymia): Combines an appetite suppressant with a drug that increases satiety. Produces moderate weight loss.
- Naltrexone-bupropion (Contrave): Combines two drugs that act on appetite and reward pathways in the brain. Moderate weight loss.
- Liraglutide (Saxenda): A daily GLP-1 injection that reduces appetite. More effective than older oral options, less than the newer weekly GLP-1s.
- Semaglutide (Wegovy): A weekly GLP-1 injection with strong weight-loss results (around 15% average in trials).
- Tirzepatide (Zepbound): A weekly dual GIP/GLP-1 injection with the largest average weight loss of the group (up to about 20%+ in trials).
Comparison table
| Drug | How it works | Form | Relative weight loss |
|---|---|---|---|
| Orlistat (Xenical/Alli) | Blocks fat absorption | Oral | Modest |
| Qsymia | Appetite suppression + satiety | Oral | Moderate |
| Contrave | Appetite/reward pathways | Oral | Moderate |
| Saxenda (liraglutide) | Daily GLP-1 | Injection | Moderate to high |
| Wegovy (semaglutide) | Weekly GLP-1 | Injection | High (~15% avg) |
| Zepbound (tirzepatide) | Weekly GIP + GLP-1 | Injection | Highest (~20%+ in trials) |
Which produces the most weight loss?
The GLP-1-class drugs lead by a wide margin, and within that class, tirzepatide (Zepbound) has produced the greatest average weight loss, ahead of semaglutide (Wegovy) in head-to-head data. Liraglutide (Saxenda), an older daily GLP-1, produces less than the newer weekly options. The non-GLP-1 oral drugs (orlistat, Qsymia, Contrave) generally produce more modest results, though they remain useful options, especially where cost, tolerance, or other health factors matter.
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Take the Assessment →Alternatives to Zepbound
People often ask about alternatives to Zepbound. Within the approved list, Wegovy (semaglutide) is the closest in effectiveness, followed by Saxenda (liraglutide). The oral options (Qsymia, Contrave, orlistat) are alternatives with different mechanisms and generally lower weight loss but lower cost or different side-effect profiles. The newest developments include an oral GLP-1 (orforglipron) and other pipeline drugs, so the menu of options is expanding.
How to choose
The right drug depends on several factors:
- How much weight you want to lose. GLP-1 drugs lead for larger goals.
- Form preference. Injection (GLP-1s) versus oral (older options).
- Other health conditions. Some drugs suit certain conditions better and some are contraindicated in others.
- Tolerance. Side-effect profiles differ; GLP-1s are mostly gastrointestinal.
- Cost and coverage. GLP-1s are pricier; older oral drugs are often cheaper.
This is a decision to make with a provider who knows your full history.
Where FormBlends fits
If you are comparing weight-loss medications, FormBlends keeps plain-language guides on each option and a provider comparison tool so you can weigh effectiveness, cost, and access, including information on compounded semaglutide.
Frequently asked questions
What are the FDA-approved weight-loss drugs?
Orlistat (Xenical, Alli), phentermine-topiramate (Qsymia), naltrexone-bupropion (Contrave), liraglutide (Saxenda), semaglutide (Wegovy), and tirzepatide (Zepbound).
Which weight-loss drug works best?
The GLP-1-class drugs produce the most weight loss, with tirzepatide (Zepbound) leading semaglutide (Wegovy) in head-to-head data.
What are alternatives to Zepbound?
Wegovy (semaglutide) is the closest in effectiveness, then Saxenda (liraglutide). Oral options like Qsymia, Contrave, and orlistat are alternatives with different mechanisms.
Is there a generic for Wegovy?
Branded semaglutide remains under patent, so there is no standard generic. Compounded semaglutide emerged as a lower-cost route during shortages.
Which weight-loss drugs are pills?
Orlistat, Qsymia, and Contrave are oral. An oral GLP-1 (orforglipron) is among newer developments.
How do I compare these drugs?
Look at expected weight loss, form (injection vs oral), other health conditions, side effects, and cost, with a provider's guidance.
Are the older drugs still useful?
Yes. Orlistat, Qsymia, and Contrave remain options, especially where cost, tolerance, or specific health factors favor them.
Which is best for me?
That depends on your goals, health, tolerance, and budget. Discuss the options with a provider to find the right fit.
Related guides
- Semaglutide vs Phentermine vs Contrave: Three Generations of Weight Loss Drugs Compared
- Saxenda vs Zepbound vs Wegovy: Complete 2026 Comparison
- Contrave vs Wegovy: Mechanism, Efficacy, and Which Works for Weight Loss That Won't Respond to Willpower Alone
- GLP-1 Drugs vs Bariatric Surgery vs Diet & Exercise: Three Paths to Weight Loss Compared
- Retatrutide vs CagriSema vs Survodutide: Three Next-Gen Weight Loss Drugs Compared
- Wegovy to Zepbound: The Switch Within Obesity-Indicated Drugs
Sources
- NIDDK, prescription medications to treat overweight and obesity: https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
- New England Journal of Medicine, SURMOUNT-5 head-to-head trial: https://www.nejm.org/doi/full/10.1056/NEJMoa2416394
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