Six prescription medications are currently FDA-approved for long-term weight management, and they vary widely in how they work, how much weight they help you lose, and how much they cost. The most effective options, semaglutide (Wegovy) and tirzepatide (Zepbound), produce average weight loss of about 15% to 21% of body weight over roughly 68 to 72 weeks. Older oral medications and over-the-counter supplements exist too, but the evidence behind them is far weaker. Here’s what actually works, what doesn’t, and what to expect from each option.
GLP-1 Medications: The Most Effective Options
The biggest shift in weight loss treatment has come from drugs that mimic a gut hormone called GLP-1. This hormone targets areas of the brain that regulate appetite and food intake, making you feel full sooner and reducing cravings between meals. Two GLP-1 drugs are approved specifically for weight loss: semaglutide (Wegovy) and liraglutide (Saxenda). A newer drug, tirzepatide (Zepbound), targets both GLP-1 and a second hormone called GIP, which appears to amplify the effect.
In clinical trials, tirzepatide at its maximum dose reduced body weight by an average of 20.9% over 72 weeks. Semaglutide produced an average loss of 14.9% over 68 weeks. To put that in perspective, for someone weighing 250 pounds, that’s roughly 37 to 52 pounds. These are currently taken as weekly injections rather than daily pills, though oral versions are in development and lower-dose oral forms are beginning to reach the market.
The main downside is gastrointestinal side effects. Nausea, vomiting, diarrhea, and constipation are by far the most common complaints. These tend to be worst when starting or increasing the dose and often improve over time. Less common but more serious risks include inflammation of the pancreas, slowed stomach emptying (gastroparesis), bowel obstruction, and gallstone attacks. Rapid fat loss in the face can also create a hollowed appearance sometimes called “Ozempic face,” with more visible wrinkles, sunken eyes, and sagging along the jaw.
Neither Wegovy nor Zepbound should be taken by anyone with a personal or family history of medullary thyroid cancer or a condition called multiple endocrine neoplasia syndrome type 2.
Oral Prescription Pills
If you’re looking specifically for pills you swallow daily, three FDA-approved options are available for long-term use. They produce less dramatic results than GLP-1 injections but are generally cheaper and more accessible.
Phentermine-topiramate (Qsymia) combines a stimulant that suppresses appetite with an anticonvulsant medication. It’s the most effective oral option, producing roughly 7% to 9% body weight loss over a year. For a 250-pound person, that translates to about 18 to 23 pounds. It’s not suitable for people with glaucoma, overactive thyroid, or those who have recently taken certain antidepressants called MAOIs.
Naltrexone-bupropion (Contrave) pairs a medication used to treat alcohol and drug dependence with an antidepressant also used for smoking cessation. Together, they work on brain pathways involved in cravings and reward. The results are more modest: about 4% to 5% total body weight loss over a year, or roughly 10 to 13 pounds for someone at 250 pounds. This one has a longer list of restrictions. It shouldn’t be taken by people with uncontrolled high blood pressure, a history of seizures, eating disorders, or those who use opioids frequently.
Orlistat (Xenical) works completely differently from the other options. Instead of acting on the brain, it blocks enzymes in your gut that digest fat, preventing your body from absorbing roughly 30% of the dietary fat you eat. That unabsorbed fat passes through your system, which is why the most notable side effects involve oily or loose stools, gas, and urgency. A lower-dose version (Alli) is available over the counter. Orlistat won’t help much if your diet is already low in fat, and it can interfere with absorption of fat-soluble vitamins.
Over-the-Counter Supplements
Dozens of supplements are marketed for weight loss, but the clinical evidence behind them is consistently disappointing. The most studied ingredients tell a clear story: any effects are tiny and unlikely to matter in the real world.
Green tea extract is one of the most popular. A large review of 14 trials covering over 1,500 people found it reduced body weight by less than 1 kilogram (about 2 pounds) more than a placebo over 12 to 13 weeks. When researchers looked only at the higher-quality studies conducted outside Japan, the difference disappeared entirely. Further research suggests that green tea catechins without caffeine have no measurable effect on weight at all. A year-long trial of decaffeinated green tea extract in postmenopausal women with overweight or obesity showed no effect on body weight, BMI, or waist size.
Garcinia cambogia, another common ingredient, fared similarly. A meta-analysis of 12 trials found it reduced weight by an average of 0.88 kg (under 2 pounds) compared to placebo over 2 to 12 weeks. But when only the two most rigorously designed trials were considered, the effect was no longer statistically significant.
The bottom line on supplements: none come close to matching even the weakest prescription medications, and many have no proven benefit at all beyond what you’d get from a sugar pill.
What These Medications Cost
Cost is often the biggest barrier. Wegovy and Zepbound have been running about $500 a month in most cases, though recent pricing changes are bringing that down. Manufacturer direct-purchase programs are expected to offer these drugs for an average of around $350 a month depending on dose, with the lowest doses of upcoming pill forms potentially available for as little as $149 a month.
Older oral medications like Contrave and Qsymia tend to be significantly less expensive, and generic orlistat is the cheapest prescription option. Insurance coverage varies widely. Some plans cover weight loss medications, especially if you have obesity-related health conditions like type 2 diabetes or high blood pressure, while others exclude them entirely.
Watch Out for Compounded Versions
The high cost of brand-name GLP-1 drugs has created a booming market for compounded versions, which are custom-mixed by pharmacies. These are not FDA-approved, meaning no one reviews them for safety, effectiveness, or quality before they’re sold. The FDA has flagged serious concerns: some compounded products have arrived at incorrect temperatures, which can degrade the drug. Others carried completely fraudulent labels, listing pharmacies that either don’t exist or didn’t actually make the product.
As of July 2025, the FDA has received 605 adverse event reports tied to compounded semaglutide and 545 tied to compounded tirzepatide. Many of these involved dosing errors, where patients or even healthcare providers miscalculated the correct amount. Some compounders have also been using salt forms of semaglutide (like semaglutide sodium or semaglutide acetate) that are chemically different from the active ingredient in the approved drugs, with unknown safety profiles.
Products labeled “for research purposes” or “not for human consumption” but sold with dosing instructions are also illegal and have drawn FDA warnings. If you’re considering a compounded product to save money, the risks are real and documented.
Who Qualifies for Prescription Weight Loss Drugs
Prescription weight loss medications are generally prescribed for adults with a BMI of 30 or higher (classified as obesity), or a BMI of 27 or higher if you also have at least one weight-related health condition such as type 2 diabetes, high blood pressure, or high cholesterol. Your doctor will also consider your medical history to rule out contraindications specific to each drug. Most of these medications are meant to be used alongside dietary changes and increased physical activity, not as a standalone fix. If you stop taking them, weight regain is common, which is why many people stay on them long-term.