Six FDA-approved medications are available for long-term weight loss, and the most effective ones can help people lose 10% to 15% of their body weight over one to two years. Three of these are pills you swallow, while the other three are weekly or daily injections. There’s also one over-the-counter option. Here’s what each one does, how well it works, and what to expect.
Pills You Take by Mouth
If you specifically want a pill rather than an injection, three prescription options are approved for long-term use.
Phentermine-topiramate (Qsymia) is the most effective oral pill for weight loss. It combines an appetite suppressant with a medication originally developed for seizures and migraines. Together, they reduce hunger and help you feel full sooner. In clinical trials, people taking the higher dose lost 9% to 11% of their body weight over one year, compared to just 1% to 2% for people taking a placebo. You take it once daily.
Naltrexone-bupropion (Contrave) works on two brain systems at once: the appetite-regulating center and the reward system that drives food cravings. It pairs an addiction-treatment drug with an antidepressant, and the combination reduces both physical hunger and the emotional pull toward food. Weight loss is more modest than with phentermine-topiramate, but for people whose weight struggles are tied to cravings and emotional eating, it targets those patterns directly. You take it once or twice daily.
Orlistat (Xenical) takes a completely different approach. Instead of acting on your brain, it works in your gut by blocking about 30% of the fat you eat from being absorbed. You take it three times a day with meals. The tradeoff: weight loss is smaller, typically 2 to 5 kilograms (about 4 to 11 pounds) more than dieting alone over a year. It also causes oily or fatty stools if you eat high-fat meals, which most people find unpleasant. A lower-dose version called Alli is available without a prescription, making it the only over-the-counter weight loss medication with FDA approval.
Injectable Medications That Produce Larger Results
The newest and most powerful weight loss medications aren’t pills. They’re self-injected at home using a small pen device, similar to what people with diabetes use.
Tirzepatide (Zepbound) produces the largest weight loss of any approved medication. It mimics two gut hormones that regulate appetite, and in real-world data, patients lost an average of 14.7% of their body weight (about 16 kg or 35 pounds) over two years. Roughly 43% of people on tirzepatide lost 15% or more of their weight, and about one in four lost 20% or more. You inject it once a week.
Semaglutide (Wegovy) mimics one of those same gut hormones, and it’s the medication that kicked off the current wave of weight loss drugs. Average weight loss over two years is about 10.8% of body weight (around 11.6 kg or 25 pounds). About 47% of users lose 10% or more. It’s also a once-weekly injection.
Liraglutide (Saxenda) works through the same hormone pathway as semaglutide but requires a daily injection and generally produces less weight loss. It was the first in this class approved for weight management and remains an option, though many prescribers now favor the weekly alternatives.
Common Side Effects
The injectable medications that mimic gut hormones share a well-known pattern of digestive side effects. In a large real-world study of more than 10,000 patients, abdominal pain affected about 58%, diarrhea about 33%, constipation 30%, and nausea or vomiting roughly 23%. These symptoms are usually worst during the first few weeks and when the dose increases, then tend to ease over time. Starting at a low dose and increasing gradually helps, which is why all of these medications use a step-up dosing schedule.
Phentermine-topiramate can cause tingling in the hands and feet, dry mouth, constipation, and trouble sleeping. Naltrexone-bupropion commonly causes nausea, headache, and constipation. Orlistat’s side effects are almost entirely digestive: oily stools, gas, and urgent bowel movements, especially after fatty meals.
People with a personal or family history of a type of thyroid cancer called medullary thyroid carcinoma should not use the injectable gut-hormone medications. Your prescriber will ask about this before writing a prescription.
Who Qualifies for These Medications
Weight loss medications are generally prescribed for adults with a BMI of 30 or higher, or a BMI of 27 or higher when a weight-related health condition like type 2 diabetes, high blood pressure, or high cholesterol is also present. Several of these medications, including semaglutide, phentermine-topiramate, and orlistat, are also approved for adolescents ages 12 and older.
Short-term appetite suppressants like phentermine (sold as Adipex-P) are FDA-approved only for a few weeks of use. They can jump-start weight loss but aren’t designed as long-term solutions.
Why Over-the-Counter Supplements Are Different
Dietary supplements marketed for weight loss, including green tea extract, garcinia cambogia, and countless “fat burner” blends, are not held to the same standard as prescription medications. The FDA does not require supplement manufacturers to prove their products work before selling them. This means the weight loss claims on supplement labels are largely unverified, and the actual contents of the product may not match the label. No over-the-counter weight loss supplement has the kind of large-scale clinical trial data behind it that prescription medications do. Alli (low-dose orlistat) is the sole exception, since it went through the full FDA drug approval process.
What to Realistically Expect
Even the most effective medications work best alongside changes to eating and physical activity. In every clinical trial behind these drugs, participants also followed a reduced-calorie diet and exercised. The medication handles the biological side of the equation, reducing hunger signals and cravings that make sustained calorie reduction so difficult, but it doesn’t replace the need for behavioral changes.
Weight loss with these medications is gradual. Most people see meaningful results over three to six months, with weight continuing to decrease for up to a year or two. If you stop taking the medication, the appetite suppression goes away, and most people regain some or all of the weight. This is why the six long-term medications are designed to be used indefinitely, much like blood pressure medication. The choice between a pill and an injection often comes down to how much weight you need to lose: the oral pills produce solid results in the range of 5% to 11% body weight loss, while the injectables can push well beyond that for many people.