The most effective things you can take to lose weight are prescription medications, particularly a newer class of injectable drugs that produce 14% to 20% body weight loss over about 18 months. But options range from over-the-counter pills to supplements to prescriptions, and what makes sense for you depends on how much weight you need to lose, your health history, and what you can access. Here’s what actually works, what barely moves the needle, and what to realistically expect.
Prescription Injectables: The Most Effective Option
Injectable medications that mimic gut hormones are, by a wide margin, the most powerful weight loss drugs available. Two dominate the market right now: semaglutide (brand name Wegovy) and tirzepatide (brand name Zepbound). Both work by activating receptors in the brain that regulate hunger and fullness, making you feel satisfied with less food.
In a head-to-head comparison over 72 weeks, people taking tirzepatide lost an average of 20.2% of their body weight, while those on semaglutide lost 13.7%. For someone starting at 250 pounds, that translates to roughly 34 to 50 pounds. These drugs are taken as a weekly self-injection, and your dose gets gradually increased over several months until you reach the target level.
Weight loss typically continues for about 60 weeks before plateauing. Once you hit the maximum dose, there’s no further adjustment available, and weight tends to stabilize. The most common side effects are nausea, vomiting, and diarrhea, which are usually worst during dose increases and improve over time. The FDA warns against using these medications if you have a personal or family history of medullary thyroid cancer or a rare condition called MEN2, though newer research suggests the thyroid concern in humans may be overstated.
One important shift in clinical guidance: the American College of Cardiology now says patients should not be required to “try and fail” with diet and exercise before starting these medications. Data from large trials showed minimal additional weight loss when intensive lifestyle coaching was added on top of the drugs. That said, healthy eating and movement are still recommended alongside medication.
Prescription Pills
If injectables aren’t an option, several oral prescription medications can help, though they produce more modest results.
Phentermine-topiramate (brand name Qsymia) is the most effective oral option. It combines an appetite suppressant with a drug originally used for seizures that also reduces cravings. In clinical trials, for every three people who took it, one additional person achieved at least 10% body weight loss compared to placebo. It’s typically prescribed for short-term use and can raise heart rate and cause tingling in the hands and feet.
Naltrexone-bupropion (brand name Contrave) pairs an addiction medication with an antidepressant, targeting the brain’s reward system to reduce food cravings. It’s slightly less effective than Qsymia: for every four people taking it, one additional person lost at least 10% of body weight. Nausea is the most common reason people stop taking it. Both medications have discontinuation rates roughly 2.5 times higher than placebo due to side effects.
The One Over-the-Counter Drug
Orlistat (brand name Alli) is the only FDA-approved, non-prescription weight loss medication. It works completely differently from everything above. Instead of affecting your brain or appetite, it blocks your body from absorbing about 25% of the fat you eat. You take a 60-milligram pill within an hour of each fat-containing meal, up to three times a day.
The weight loss is modest, typically 5 to 7 pounds more than dieting alone over a year. And the side effects are the real barrier for most people. Because undigested fat passes straight through your digestive system, you can expect oily stools, oily discharge, gas with oily spotting, and urgent bowel movements. These effects are directly tied to how much fat you eat. A high-fat meal on Alli can mean an unpleasant few hours. Most people find these side effects lessen over time, and some actually consider them useful feedback that discourages fatty food choices.
Supplements That Show Some Evidence
The supplement aisle is packed with weight loss products, but very few have meaningful clinical data behind them. Two stand out as having at least some research support, though neither comes close to prescription medications.
Berberine, a compound found in several plants, gained popularity on social media as “nature’s Ozempic,” which is a massive exaggeration. A review of 18 studies did find that berberine produced significant decreases in body weight and BMI, but only at doses above 1 gram per day taken for more than 8 weeks. The reviewers noted that many of the studies had a high risk of bias and inconsistent results, so the evidence is far from definitive. The weight loss amounts were small, nothing remotely comparable to prescription options.
Green tea extract has slightly better mechanistic data. A study published in the American Journal of Clinical Nutrition found that a green tea extract containing catechin polyphenols and caffeine increased 24-hour calorie burning by about 4%, which worked out to roughly 78 extra calories per day. Interestingly, caffeine alone at the same dose had no effect on energy expenditure, suggesting the active compounds in green tea are doing the work, not just the caffeine. An extra 78 calories per day adds up slowly. Over a month, that’s the equivalent of about two-thirds of a pound, assuming nothing else changes.
Other popular supplements like garcinia cambogia, raspberry ketones, and apple cider vinegar pills have either failed in controlled trials or simply lack enough quality research to recommend.
What to Realistically Expect
The timeline for weight loss varies dramatically depending on what you take. With the most effective injectable medications, you’ll typically see steady loss for about 14 to 15 months before weight stabilizes. Oral prescriptions tend to plateau earlier, and the total loss is smaller. Over-the-counter options and supplements work slowly enough that it can be hard to distinguish their effect from normal weight fluctuation in the first few weeks.
All weight loss medications share one uncomfortable truth: when you stop taking them, weight tends to come back. Studies on semaglutide show that people regain about two-thirds of their lost weight within a year of stopping. This is why current clinical thinking treats obesity as a chronic condition requiring ongoing management, similar to blood pressure medication, rather than a short course of treatment you complete and move on from.
Cost is the other major factor. Injectable medications can run over $1,000 per month without insurance, and coverage varies widely. Oral prescriptions are generally cheaper but still significant. Alli costs roughly $40 to $60 per month. Supplements are the least expensive but also the least effective.
Choosing What’s Right for You
If you have a BMI over 30, or over 27 with a weight-related health condition like type 2 diabetes or high blood pressure, you’re likely eligible for prescription options. Your starting point matters: someone with 15 pounds to lose is in a very different situation than someone with 80 pounds to lose, and the risk-benefit calculation shifts accordingly.
For smaller amounts of weight loss, the side effect profiles of prescription drugs may not be worth it. Alli, combined with a reduced-calorie diet, can provide a modest boost. Supplements like green tea extract or berberine are unlikely to cause harm at standard doses but are also unlikely to produce dramatic results on their own.
For significant weight loss, the injectable medications are in a category of their own. Nothing else currently available, whether prescription, over-the-counter, or supplement, comes close to the 14% to 20% body weight reduction seen in clinical trials of semaglutide and tirzepatide.