The FDA has approved six medications for long-term weight management, plus one for rare genetic conditions and one older drug limited to short-term use. The options range from daily pills that block fat absorption to weekly injections that can produce 20% or more body weight loss. A newer oral version of semaglutide was also recently approved, making it the first GLP-1 pill for weight management.
To qualify for most of these medications, you need a BMI of 30 or higher, or a BMI of 27 or higher with at least one weight-related condition such as high blood pressure, type 2 diabetes, or high cholesterol.
Injectable GLP-1 and Dual-Agonist Drugs
The most effective weight loss medications currently available work by mimicking gut hormones that regulate appetite and blood sugar. These drugs slow stomach emptying, reduce hunger signals in the brain, and help you feel full sooner and longer.
Semaglutide (Wegovy) is a once-weekly injection. In clinical trials, participants lost an average of 12.4% more body weight than those on placebo over 68 weeks. It’s approved for adults and adolescents aged 12 and older.
Tirzepatide (Zepbound) is also a once-weekly injection but targets two gut hormones instead of one. In the SURMOUNT-1 trial, participants on the highest dose lost an average of 20.9% of their body weight over 72 weeks, making it the most potent approved option. One in five people in that trial lost roughly a quarter of their starting weight.
Liraglutide (Saxenda) works through the same pathway as semaglutide but requires a daily injection and produces more modest weight loss. It was approved for adults in 2014 and expanded to adolescents aged 12 and older in 2020. Because newer options tend to be more effective, liraglutide is now prescribed less frequently, though it remains a reasonable choice for people who prefer not to use the newer drugs.
The New Oral Semaglutide Pill
The FDA recently approved an oral form of Wegovy, a once-daily 25 mg semaglutide tablet. This is the first GLP-1 pill approved specifically for weight management. In the OASIS 4 trial, it produced 16.6% mean weight loss, comparable to the injectable version. About one in three participants lost 20% or more of their body weight. For people who don’t want to give themselves injections, this is a significant development.
Oral Combination Medications
Phentermine-topiramate (Qsymia) combines a stimulant that suppresses appetite with an anticonvulsant that also reduces hunger. It’s taken as a daily capsule and is approved for adults and adolescents aged 12 and older. Weight loss typically falls in the 5% to 10% range, less dramatic than the injectable options but meaningful enough to improve metabolic health markers.
Naltrexone-bupropion (Contrave) pairs an antidepressant with an opioid-blocking drug. Together they act on brain circuits involved in appetite and reward. Bupropion stimulates cells that produce satiety signals, while naltrexone prevents the brain from dampening those signals through its own feedback loop. Weight loss averages around 5% to 6% beyond what diet and exercise alone achieve. This option is sometimes preferred for people who also struggle with food cravings tied to emotional or reward-driven eating.
Orlistat: The Fat Blocker
Orlistat works differently from every other drug on this list. Instead of targeting hunger or hormones, it blocks enzymes in your gut that break down dietary fat. At the recommended dose, about 30% of the fat you eat passes through unabsorbed. It’s available by prescription as Xenical and over the counter at a lower dose as Alli.
The trade-off is gastrointestinal side effects. Undigested fat has to go somewhere, so oily stools, gas, and urgent bowel movements are common, especially after high-fat meals. Weight loss is modest compared to newer medications. Many people find it difficult to tolerate long-term, which is partly why prescribing has shifted toward the hormone-based drugs.
Short-Term Option: Phentermine
Phentermine on its own is FDA-approved only for short-term use, up to 12 weeks. It’s a stimulant that suppresses appetite, and it’s been available since the 1950s. Because of its stimulant properties, it can raise heart rate and blood pressure. It’s sometimes used as a bridge while patients wait to start or titrate up to one of the long-term medications, but it’s not intended as an ongoing treatment.
Setmelanotide for Rare Genetic Obesity
Setmelanotide (Imcivree) occupies a narrow lane. It’s approved only for people aged 6 and older who have obesity caused by one of four specific rare genetic disorders, confirmed through genetic testing. These conditions disrupt the brain’s hunger-signaling pathway, and setmelanotide works by restoring part of that pathway. Most people searching for weight loss medications won’t encounter this drug, but it can be transformative for those with a qualifying diagnosis.
Side Effects of GLP-1 Based Drugs
Nausea is the most common side effect across all the GLP-1 and dual-agonist medications, including semaglutide, tirzepatide, and liraglutide. It tends to be worst during the first few weeks and during dose increases, then often fades as your body adjusts. Vomiting and reduced appetite are also frequent early on. Most prescribers start at a low dose and increase gradually to minimize these effects.
Pancreatitis has received attention as a potential risk. The actual incidence is low. In large clinical trials, acute pancreatitis occurred in roughly 0.3% to 0.4% of participants on these medications. One semaglutide weight loss trial found 3 cases among 1,306 participants, with none in the placebo group. The risk is real but rare, and symptoms to watch for include severe, persistent abdominal pain that radiates to the back.
How These Drugs Compare
- Most weight loss: Tirzepatide (Zepbound) at the highest dose, averaging about 21% body weight reduction.
- Strong weight loss, most data: Semaglutide (Wegovy), both injectable and the new oral pill, averaging 12% to 17% beyond placebo.
- Oral options without injections: The new Wegovy pill, Qsymia, and Contrave. Orlistat is also oral but less effective.
- Available over the counter: Only Alli (low-dose orlistat).
- Approved for ages 12 and up: Wegovy, Qsymia, Saxenda.
All of these medications are designed to be used alongside diet and exercise changes, not as replacements for them. Weight tends to return after stopping the medication, which is why most of these drugs are approved for long-term, ongoing use. Your prescriber will typically reassess after a few months to see if the drug is producing enough weight loss to justify continuing.