Several prescription drugs can help you lose weight, and the most effective ones available right now are injectable medications that mimic gut hormones to reduce appetite. The FDA has approved six medications for long-term weight management, plus a few others for short-term or specialized use. Which one fits your situation depends on how much weight you need to lose, whether you’re comfortable with injections, and your medical history.
The Two Most Effective Options
Semaglutide (brand name Wegovy) and tirzepatide (brand name Zepbound) are the heavy hitters. Both are weekly injections that work by mimicking a hormone your gut naturally releases after eating. This hormone signals your brain’s satiety center, making you feel full sooner and reducing the mental “noise” around food and cravings. In clinical trials, tirzepatide produced average weight loss of roughly 20% of body weight, while semaglutide produced around 15%.
Tirzepatide mimics two gut hormones instead of one, which likely explains the extra edge. Both drugs are started at a low dose and gradually increased over several months to minimize side effects. With Wegovy, you typically start at 0.25 mg per week and work up to a maintenance dose of 1.7 mg or 2.4 mg over about 16 weeks. A higher-dose version (7.2 mg) was approved in March 2026 for people who tolerate the standard dose and want additional weight loss. Zepbound follows a similar pattern, starting at 2.5 mg weekly and potentially increasing to 5, 10, or 15 mg.
Wegovy also comes in an oral tablet form for people who prefer not to inject. The tablet version starts at 1.5 mg daily and ramps up to 25 mg daily over about three months.
Oral Prescription Pills
If injections aren’t an option or you’d prefer a pill, three other FDA-approved medications are available for long-term use.
- Phentermine-topiramate (Qsymia) combines an appetite suppressant with a medication originally developed for seizures and migraines. Taken once daily, it reduces hunger through two different pathways. It tends to produce more weight loss than the other oral options.
- Naltrexone-bupropion (Contrave) pairs a drug used in addiction treatment with an antidepressant. Together, they act on brain circuits involved in cravings and reward. This can be a good fit if emotional eating or food cravings are a significant part of the picture.
- Orlistat (Xenical) works differently from everything else on this list. Instead of targeting your brain, it blocks your gut from absorbing about a third of the fat you eat. It’s taken three times a day with meals. The trade-off: unabsorbed fat has to go somewhere, so oily stools, gas, and urgent bowel movements are common, especially if you eat high-fat meals. A lower-dose version (Alli) is available over the counter.
Phentermine by itself (Adipex-P, Lomaira) is approved only for short-term use, generally less than 12 months. It suppresses appetite and can help jump-start weight loss, but it’s not a long-term solution on its own.
How These Drugs Actually Feel
The injectable medications (semaglutide and tirzepatide) tend to change your relationship with food in a way that feels surprisingly natural. People commonly describe simply not thinking about food as much, feeling satisfied with smaller portions, and losing interest in snacking. The effect builds gradually as the dose increases.
The most common side effects for the injectables are nausea, vomiting, diarrhea, and constipation. These are usually worst during the first few weeks on a new dose and fade as your body adjusts. The slow dose increases are specifically designed to give your system time to adapt. Eating smaller meals and avoiding greasy or very rich food helps.
The oral pills have their own profiles. Phentermine-topiramate can cause tingling in your hands and feet, dry mouth, and constipation. Naltrexone-bupropion commonly causes nausea and headaches early on. Orlistat’s digestive side effects are the most distinctive and directly tied to how much fat you eat.
Who Shouldn’t Take Them
GLP-1 based medications (semaglutide, tirzepatide, and liraglutide) carry a boxed warning about thyroid cancer. In animal studies, these drugs caused thyroid tumors. Whether the same risk applies to humans isn’t fully known, but anyone with a personal or family history of medullary thyroid cancer or a condition called multiple endocrine neoplasia type 2 should not use these medications.
Pregnancy rules out all weight loss drugs. Phentermine-topiramate specifically carries a risk of birth defects. Naltrexone-bupropion shouldn’t be used by anyone with uncontrolled high blood pressure or a seizure disorder. Each medication has its own list of interactions, so your prescriber will review your full medical history before choosing one.
What About Over-the-Counter Options
The only FDA-approved over-the-counter weight loss drug is Alli, a lower-dose version of orlistat. It blocks fat absorption the same way the prescription version does, just less aggressively. You can expect modest weight loss, typically a few extra pounds beyond what diet and exercise alone would achieve.
Supplements marketed as fat burners, appetite suppressants, or metabolism boosters are not FDA-approved for weight loss. They don’t go through the same testing for safety or effectiveness, and most have little evidence behind them. Some contain stimulants or hidden ingredients that can be genuinely dangerous.
What Realistic Weight Loss Looks Like
Prescription weight loss medications are approved for people with a BMI of 30 or higher, or 27 or higher with at least one weight-related health condition like high blood pressure, type 2 diabetes, or high cholesterol. They’re designed as additions to diet and exercise changes, not replacements for them.
The newer injectables produce the most dramatic results. With tirzepatide, roughly one in three participants in clinical trials lost more than 25% of their body weight. Semaglutide typically produces 12% to 15% loss. The older oral medications generally produce 5% to 10%, which is still enough to meaningfully improve blood pressure, blood sugar, and joint pain.
One important reality: weight tends to come back if you stop taking these medications. Studies on semaglutide found that participants regained about two-thirds of their lost weight within a year of stopping. This means most people need to think of these drugs as long-term treatments rather than short courses. Cost and insurance coverage remain significant barriers, with monthly prices for the injectables often running over $1,000 without coverage.