Several prescription medications suppress appetite, ranging from older stimulant-based pills approved for short-term use to newer injectable drugs designed for long-term weight management. The most effective options currently available are injectable medications that mimic gut hormones, with the top performer producing an average body weight loss of about 20% over 72 weeks. Which medication fits your situation depends on your health profile, how much weight you need to lose, and how long you plan to use it.
To qualify for a prescription weight loss medication, you generally need a BMI of 30 or higher, or a BMI of 27 or higher with a weight-related condition like high blood pressure or type 2 diabetes.
Injectable Medications: GLP-1 and Dual-Action Drugs
The strongest appetite suppressants available today are injectable medications that mimic hormones your gut naturally releases after eating. These drugs slow stomach emptying, signal fullness to the brain, and reduce food cravings in ways that feel less like willpower and more like a genuine shift in hunger levels. They’re approved for long-term use, which sets them apart from older appetite suppressants.
Semaglutide (brand name Wegovy) is a once-weekly injection that targets a single gut hormone receptor. In a head-to-head clinical trial published in The New England Journal of Medicine, participants on semaglutide lost an average of 13.7% of their body weight over 72 weeks, with about 60% of users losing at least 10% of their starting weight.
Tirzepatide (brand name Zepbound) targets two gut hormone receptors instead of one. In that same head-to-head trial, tirzepatide users lost an average of 20.2% of their body weight over the same 72-week period. Nearly 65% of participants hit the 15% weight loss mark, and about 48% lost 20% or more. That makes tirzepatide the most potent appetite-suppressing medication currently on the market.
Both medications share similar side effects, mostly gastrointestinal: nausea, vomiting, diarrhea, and constipation. These tend to be worst during the first few weeks and when the dose increases. Both drugs are started at a low dose and gradually increased over several months to minimize these effects.
Oral Combination Medications for Long-Term Use
Not everyone wants or qualifies for an injectable. Two oral combination pills are approved for long-term appetite suppression, and each works through a different mechanism.
Qsymia combines two older drugs: phentermine, which suppresses appetite by boosting norepinephrine (a brain chemical involved in alertness and the fight-or-flight response), and topiramate, an anti-seizure medication that also reduces appetite through a separate brain pathway. The combination tends to produce more weight loss than either drug alone while allowing lower doses of each, which can reduce side effects. Common side effects include tingling in the hands and feet, dry mouth, constipation, and difficulty concentrating. Qsymia is not safe during pregnancy because topiramate can cause birth defects.
Contrave pairs naltrexone, which blocks opioid receptors in the brain, with bupropion, an antidepressant that affects dopamine and norepinephrine. Together, they target the brain’s reward system and hunger signals. Contrave tends to produce more modest weight loss than the injectable options, but it can be a good fit for people whose eating is driven more by cravings and reward-seeking behavior than by physical hunger. Nausea, headache, and constipation are the most common side effects.
Short-Term Appetite Suppressants
Phentermine is the oldest and most widely prescribed appetite suppressant in the United States. It works as a mild stimulant, releasing norepinephrine in the brain to reduce hunger signals. The FDA approved it only for short-term use, typically up to 12 weeks, though some clinicians prescribe it for longer periods in practice. Diethylpropion is another short-term option that works through a similar stimulant mechanism.
Because these drugs act like mild amphetamines, they carry specific safety restrictions. They’re not appropriate for people with heart disease, uncontrolled high blood pressure, structural heart abnormalities, serious arrhythmias, or a history of stroke. They’re also contraindicated in narrow-angle glaucoma, since the stimulant effect can raise pressure inside the eye. People with significant anxiety or agitation may find these medications make their symptoms worse.
The appeal of phentermine is its low cost and availability as a generic. The drawback is that it’s designed as a short-term jumpstart, not a long-term solution, and appetite typically returns when you stop taking it.
Off-Label Options
Some medications prescribed for other conditions produce appetite suppression as a side effect, and clinicians sometimes use them off-label for weight management. Metformin, a first-line diabetes drug, is the most common example. It improves how the body handles blood sugar without stimulating insulin production, and several studies have shown modest weight loss in patients taking it. The weight loss is generally smaller than what you’d see with dedicated appetite suppressants, but it can be meaningful when combined with diet and exercise changes, and it’s inexpensive and well-studied.
Clinical trial data on off-label weight loss medications in general shows that the results tend to be modest compared to FDA-approved options, though still statistically significant compared to placebo when paired with lifestyle changes. These medications are typically considered when someone doesn’t qualify for or can’t tolerate approved weight loss drugs, or when they’re already taking the medication for another condition and the appetite suppression is a welcome bonus.
Oral GLP-1 Pills in Development
One of the biggest limitations of the most effective appetite suppressants is that they require weekly injections. That may change soon. Eli Lilly is in late-stage clinical trials for orforglipron, a GLP-1 pill that works through the same mechanism as the injectable drugs but can be taken by mouth. The company is seeking FDA approval in 2025. If approved, an oral option could make this class of medication accessible to the many people who avoid injectables due to needle aversion, cost, or convenience.
How These Medications Compare
The practical differences between these medications come down to three things: how much weight they help you lose, how long you can take them, and what side effects you’re willing to tolerate.
- Tirzepatide (Zepbound): Strongest average weight loss at about 20%. Weekly injection. Approved for long-term use. Gastrointestinal side effects, especially early on.
- Semaglutide (Wegovy): Average weight loss around 14%. Weekly injection. Approved for long-term use. Similar GI side effects to tirzepatide.
- Qsymia: Moderate weight loss. Daily oral pill. Approved for long-term use. Not safe in pregnancy. Can cause tingling and cognitive fog.
- Contrave: More modest weight loss. Daily oral pill. Approved for long-term use. Best suited for craving-driven eating.
- Phentermine: Moderate appetite suppression. Daily oral pill. Short-term use only (typically 12 weeks). Not safe with heart conditions.
- Metformin: Mild weight loss. Daily oral pill. Off-label use. Best suited for people who also have blood sugar issues.
Weight tends to return after stopping any of these medications, which is why the shift in obesity medicine has moved toward drugs approved for long-term use. The newer injectable medications have redefined expectations: losing 15 to 20% of body weight was nearly unheard of with older pills, which typically produced 5 to 10% losses. But availability, cost, and insurance coverage remain real barriers for many people, making the older and less expensive options still relevant.