Free Guide to FDA Approved Weight Loss Medications

Overview of FDA-Approved Weight Loss Medications

The U.S. Food and Drug Administration (FDA) has reviewed and approved several medications specifically designed to help people manage their weight. These drugs work through different methods—some reduce appetite, others change how your body absorbs calories, and some affect how your brain signals hunger. As of 2024, there are five main FDA-approved weight loss medications available by prescription. Understanding how each one works is the first step in learning about your options.

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Weight loss medications are not diet pills sold over the counter. They are prescription drugs that doctors must prescribe and monitor. The FDA approval process means these medications have been tested in clinical trials with thousands of participants. Researchers tracked how much weight people lost, what side effects occurred, and how long the effects lasted. This rigorous testing helps ensure that approved medications are both effective and reasonably safe when used as directed.

It's important to know that weight loss medications work best when combined with lifestyle changes. Studies show that people who take these drugs and also eat healthier and exercise tend to lose more weight than people who only take medication. A person might lose 5% to 22% of their body weight depending on which medication they use, how their body responds, and how committed they are to changing their habits. These are significant results—losing even 5% of body weight can improve blood pressure and blood sugar levels.

These medications may be recommended for people with a BMI (body mass index) of 30 or higher, or those with a BMI of 27 or higher who also have weight-related health problems like diabetes or heart disease. However, only a doctor can determine whether a medication is appropriate for any individual patient, based on their complete medical history.

Practical Takeaway: FDA-approved weight loss medications are prescription drugs that work through different mechanisms. They are most effective when combined with diet and exercise changes. A doctor's evaluation is necessary to determine which medication, if any, might be suitable for a specific person.

The Five Main FDA-Approved Weight Loss Medications

The five medications currently approved by the FDA for weight loss are orlistat, phentermine, diethylpropion, phendimetrazine, and the newer GLP-1 receptor agonists (semaglutide and tirzepatide). Each has a different chemical makeup and mechanism of action, meaning they affect your body in different ways.

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Orlistat is unique because it's available without a prescription under the brand name Xenical or Alli. This medication works in your digestive system rather than in your brain. It blocks your intestines from absorbing about 30% of the fat you eat. Clinical trials showed that people using orlistat lost an average of 5.7 kg (about 12.5 pounds) over six months, compared to 2.6 kg for those taking a placebo. The main side effect is oily spotting in your underwear because unabsorbed fat passes through your system.

Phentermine has been used since 1959 and works by suppressing your appetite. It stimulates your central nervous system and reduces hunger signals. Doctors typically prescribe it for short-term use—usually 12 weeks or less, though some research supports longer-term use. Studies show people lose about 3 to 5 kg (7 to 11 pounds) more than they would with diet alone. Phentermine can cause increased heart rate, insomnia, and restlessness in some people.

Diethylpropion and phendimetrazine are older medications that work similarly to phentermine by suppressing appetite. They are prescribed less frequently than phentermine. Diethylpropion is typically used for 12 weeks or less, while phendimetrazine may be prescribed for longer periods. Weight loss with these medications ranges from 3 to 7 kg more than diet alone.

GLP-1 receptor agonists (semaglutide, brand name Wegovy, and tirzepatide, brand name Zepbound) represent the newest class of weight loss medications. Originally developed for type 2 diabetes, these drugs slow stomach emptying and increase feelings of fullness. Clinical trials showed remarkable results: participants taking semaglutide lost an average of 15 kg (33 pounds) or about 15% of body weight, while those on tirzepatide lost up to 22 kg (48 pounds) or 22% of body weight over 68 weeks. These medications are given by injection once per week.

Practical Takeaway: The five FDA-approved weight loss medications work differently—from blocking fat absorption to suppressing appetite to increasing fullness. The newer GLP-1 medications show greater average weight loss than older options. Each has distinct side effects and considerations that should be discussed with a healthcare provider.

How Each Medication Works in Your Body

Understanding the mechanism of action—how a medication actually works—helps explain both why it might help with weight loss and what side effects you might experience. Different medications target different systems in your body.

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Orlistat's mechanism is the most straightforward. When you eat fat, your digestive system normally breaks it down and absorbs it through your intestines. Orlistat inhibits pancreatic and gastric lipases, which are the enzymes responsible for breaking down dietary fats. With these enzymes blocked, about 30% of the fat in your food passes through your system unabsorbed. This means fewer calories are taken in. Because it works only in your digestive tract and not in your bloodstream or brain, orlistat has fewer systemic side effects than other options. However, this also means it has a smaller impact on weight loss.

Phentermine, diethylpropion, and phendimetrazine all work on your central nervous system. They are sympathomimetic amines, which means they mimic the effects of norepinephrine, a natural chemical that your brain uses to regulate hunger and metabolism. By increasing norepinephrine activity, these drugs suppress appetite and slightly increase energy expenditure. They essentially tell your brain that you feel fuller and more satisfied with less food. The downside is that they can also increase heart rate and blood pressure, and they may cause nervousness or sleep problems. Because of these cardiovascular effects, they're not suitable for people with certain heart conditions.

GLP-1 receptor agonists work through a different pathway altogether. GLP-1 (glucagon-like peptide-1) is a hormone your body produces naturally when you eat. It signals to your brain that you're full and also slows the rate at which your stomach empties food into your small intestine. Semaglutide and tirzepatide are synthetic versions that activate these same GLP-1 receptors. Additionally, tirzepatide also activates GIP receptors, another appetite-regulating pathway. By mimicking these natural hormones, these medications increase satiety, reduce hunger, and slow digestion—all contributing to eating less without feeling deprived. They also may improve how your body handles blood sugar.

Practical Takeaway: Medications work through different biological pathways: blocking fat absorption, suppressing appetite through brain chemistry, or mimicking natural hunger-regulating hormones. The mechanism explains both how effective a medication is and what side effects to expect.

Side Effects and Safety Considerations

All medications carry the possibility of side effects. For weight loss drugs, understanding common side effects helps you know what to expect and whether a medication might be right for you. The FDA requires that all approved medications have documented side effects from clinical trials.

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Orlistat side effects are primarily gastrointestinal. The most common are oily spotting, urgency to have a bowel movement, and fatty or oily stools, occurring in about 20% of users. These happen because fat is passing through your system unabsorbed. Eating a low-fat diet (less than 30% of calories from fat) significantly reduces these symptoms. Other possible side effects include cramping, bloating, and gas. Because orlistat is not absorbed into the bloodstream, systemic side effects are rare. It may also interfere with the absorption of fat-soluble vitamins (A, D, E, K), so taking a vitamin supplement 2 hours before or after orlistat is recommended.