Obesity and overweight are serious health conditions affecting a significant portion of the American adult population. Approximately 70% of American adults have obesity or overweight, and many of those overweight have a weight-related condition. These conditions can lead to severe health problems, including heart disease, stroke, and diabetes. Fortunately, the Food and Drug Administration (FDA) has approved several prescription medications for chronic weight management in conjunction with a reduced-calorie diet and increased physical activity. This article provides a detailed overview of these medications, their mechanisms of action, efficacy, potential side effects, and other important considerations.
Understanding the Need for Weight Loss Medications
For adults struggling with serious health problems due to their weight, prescription weight-loss drugs can be a viable option, especially when diet and exercise alone haven't yielded sufficient results. A health care provider may suggest a weight-loss drug if your body mass index (BMI) is greater than 30, or greater than 27 with at least one weight-related condition. Before prescribing any medication, your health care provider will consider your medical history and specific health challenges.
How Prescription Weight-Loss Drugs Work
Most prescription weight-loss drugs work by reducing hunger or creating a feeling of fullness, while some do both. Taking these drugs for a year can mean a loss of total body weight of 3% to 12% more than that lost with lifestyle changes alone. Losing even 5% to 10% of your total weight and keeping it off can have significant health benefits.
FDA-Approved Weight Loss Medications
Zepbound (Tirzepatide)
In December 2024, the Food and Drug Administration approved Zepbound (tirzepatide) injection for chronic weight management in adults with obesity (body mass index of 30 kilograms per square meter (kg/ m2) or greater) or overweight (body mass index of 27 kg/m2 or greater) with at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol) for use, in addition to a reduced calorie diet and increased physical activity. Zepbound activates receptors of hormones secreted from the intestine (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)) to reduce appetite and food intake.
Dosage and Administration: Zepbound is administered by injection under the skin once weekly, and the dosage must be increased over four to 20 weeks to achieve the target dosages of 5 milligram (mg), 10 mg or 15 mg once weekly.
Read also: Weight Loss Meds & BCBS
Efficacy: Zepbound’s effectiveness for chronic weight management (weight reduction and maintenance) in combination with a reduced-calorie diet and increased physical activity was established in two randomized, double-blind, placebo-controlled trials of adults with obesity or overweight with at least one weight-related condition. These studies measured weight reduction after 72 weeks in a total of 2,519 patients who received either 5 mg, 10 mg or 15 mg of Zepbound once weekly and a total of 958 patients who received once-weekly placebo injections. The larger of the two trials enrolled adults without diabetes. At the start of the trial, the average body weight was 231 pounds (105 kg) and average body mass index was 38 kg/m2. At the start of the trial in adults with type 2 diabetes, the average body weight was 222 pounds (101 kg) and average body mass index was 36 kg/m2. In the 72-week long SURMONT-1 study with over 2,500 adults, those using the highest Zepbound 15 mg dose lost an average of 21% of their body weight (21.8 kg or 48 lb). With the lower 5 mg dose, people lost an average of 15% of their body weight (15.5 kg or 34 lb).
Side Effects and Warnings: Zepbound also contains warnings for inflammation of the pancreas (pancreatitis), gallbladder problems, hypoglycemia (blood sugar that is too low), acute kidney injury, diabetic retinopathy (damage to the eye’s retina) in patients with type 2 diabetes mellitus and suicidal behavior or thinking. Zepbound causes thyroid C-cell tumors in rats. It is unknown whether Zepbound causes such tumors, including medullary thyroid cancer, in humans. Zepbound has not been studied in patients with a history of pancreas inflammation (pancreatitis) or severe gastrointestinal disease (including severe gastroparesis, a condition that affects normal movement of the muscles in the stomach). It should not be used in combination with Mounjaro or a GLP-1 receptor agonist. Zepbound should not be used in patients with a history of severe allergic reaction to tirzepatide (its active ingredient) or to any of its other ingredients. Patients should stop Zepbound immediately and seek medical help if a severe allergic reaction is suspected.
Wegovy (Semaglutide)
Wegovy is a brand name for semaglutide, a GLP-1 receptor agonist. It was FDA-approved in 2021. It is administered as an injection and approved for use in adults and children aged 12 years or more with obesity (BMI ≥30 for adults, BMI ≥ 95th percentile for age and sex for children) or some adults with excess weight (BMI ≥27) who also have weight-related medical problems.
Dosage and Administration: The dose must be increased gradually over 16 to 20 weeks to arrive at the 2.4 mg dosage. This progression can help to alleviate side effects, which include gastrointestinal symptoms, headache, dizziness, and fatigue. It is intended to be used indefinitely, in combination with a healthy diet and exercise.
Efficacy: In clinical studies, patients taking Wegovy (semaglutide) achieved an average weight loss of 14.9% of body weight at 68-weeks vs. 2.4% for placebo. More than half of the participants in Wegovy research trials achieved 15% weight loss and one third achieved 20% or greater.
Read also: A guide to Mercy Care and weight loss medications.
Other Considerations: Wegovy contains semaglutide, the same active ingredient found in Ozempic (that is approved for type 2 diabetes, and for kidney and heart protection in certain patient groups).
Liraglutide (Saxenda)
Liraglutide is a daily injectable medication that acts on hormones that send signals from the gut to the brain to make the patient feel full quicker and decrease hunger signals.
Dosage and Administration: Doses start at 0.6 mg to 3 mg a day.
Efficacy: Some patients may lose 5-10% of body weight, especially with the higher dose of liraglutide. Studies in patients without diabetes showed that those using Saxenda lost about 4.1% of their weight compared to the group using placebo (an inactive pill) after one year. In another study with patients with type 2 diabetes, patients had an average weight loss of 2% over treatment with placebo at one year.
Other Considerations: Liraglutide is also approved for Type 2 Diabetes, under the brand name Victoza. Side effects include nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, and renal insufficiency.
Read also: Does BCBS Cover Weight Loss?
Phentermine
Phentermine is the oldest and most widely used weight loss medication. It was originally used as a short-term medication to jump-start weight loss, but now newer medical guidelines have added it to long-term therapy.
Side Effects: Side effects include headache, overstimulation, high blood pressure, insomnia, rapid or irregular heart rate, and tremor.
Phentermine-Topiramate (Qsymia)
Topiramate can be combined with phentermine to decrease appetite and cravings.
Dosage and Administration: Daily doses with four strengths start at 3.75 mg/23 mg to 15 mg/92 mg. Qsymia is an oral capsule taken once daily by mouth. Qsymia is taken once daily in morning with or without food; patients should avoid an evening dose as it may keep them awake. If you have not lost at least 5% of your weight or BMI after 12 weeks, your doctor may decide to stop Qsymia treatment.
Efficacy: Some patients may lose an average of 5-10% of body weight. In one year clinical trials, Qsymia weight loss in adults averaged 11.2 lbs to 24 lbs (5.1 kg to 10.9 kg).
Side Effects: Side effects include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth.
Other Considerations: Adults with migraines and obesity are good candidates for this weight-loss medication. Qsymia is classified as CIV controlled substance due to the phentermine component, which is an amphetamine derivative.
Naltrexone-Bupropion (Contrave)
Naltrexone-bupropion combines an opioid receptor antagonist with an antidepressant to affect the pleasure-reward areas of the brain and thereby decrease cravings and appetite. Bupropion is an antidepressant medicine that can also lower your appetite. When used together, these medications act on two areas of the brain to help with weight loss.
Dosage and Administration: Start with a daily dose of one 8/90 mg tablet and gradually increase to four tablets a day.
Side Effects: The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.
Indications: Contrave is approved to be used in adults with obesity (BMI: 30 kg/m2 or greater) or overweight (BMI: 27 kg/m2 or greater) and at least one weight-related condition such as high blood pressure, high cholesterol, or type 2 diabetes.
Orlistat (Xenical, Alli)
Orlistat is a lipase inhibitor that comes in a capsule.
Dosage and Administration: An over-the-counter formulation is available at 60 mg capsules with each fat-containing meal. alli (orlistat) is the over-the-counter (OTC) version of the FDA-approved prescription drug Xenical 120 mg but it comes in a lower 60 milligram (mg) strength. alli is taken as one 60 mg capsule three times a day with each meal containing fat. Do not take more than 3 capsules per day. Use alli in combination with diet and exercise. It is also recommended to take a daily multivitamin at bedtime to help offset the loss of any fat-soluble vitamins. The vitamin should contain the fat soluble vitamins like A, D, E, K & beta carotene. Undigested fat is then passed through the body.
Efficacy: Some patients may lose about 5% of their body weight.
Side Effects: Side effects with alli may often hinder its use and include loose stools, oily spotting, gas, bowel incontinence, and rarely liver injury (jaundice).
Setmelanotide (Imcivree)
Setmelanotide is a melanocortin-4 receptor agonist indicated for chronic weight management in adult and pediatric patients six years and older, with obesity due to certain rare genetic disorders. It can lessen your appetite and make you feel fuller.
Dosage and Administration: You take setmelanotide as a daily shot. Never give setmelanotide to a child under 6 years old.
Plenity
A medical device rather than a medication, Plenity was FDA-cleared in 2019 for people with a BMI of 25 to 40. It consists of a capsule that releases a biodegradable, super-absorbent hydrogel into the stomach. The gel helps to increase satiety, enabling the person to eat less.
Newer Weight Loss Treatments and Medications in Development
The pharmacological treatment of obesity is a fast-changing landscape, and care providers must strive continuously to stay current. With consumer demand for weight loss medications combined with rising obesity rates, more medications are bound for the market in the coming years. Pharmaceutical platform Ozmosi predicts one to two GLP-1 launches annually starting in 2026 specifically for obesity. Lilly is developing at least two new options. The first, orforglipron, is an oral GLP-1 inhibitor that completed a Phase 3 clinical trial in early 2025. It could provide a welcome alternative for people who do not want injections. The other, retatrutide, targets GLP-1, GIP, and glucagon. At this writing, it is in Phase 3 clinical trials. Amgen is developing MariTide, a monoclonal antibody designed to increase GLP-1 receptor activity while reducing GIP receptor activity. The once-monthly injection entered Phase 3 clinical trials in March 2025. Researchers continue to study hormones that play a role in appetite for other ways to target obesity with medication. Those of interest include not only GLP-1, but also peptide tyrosine-tyrosine (PYY) and cholecystokinin (CCK).
Compounded Semaglutide and Tirzepatide: Risks and Concerns
With fervent consumer demand for weight loss medications, combined with rising obesity rates, compounded versions of semaglutide and tirzepatide have emerged. However, the FDA warns against buying medications from any source other than a state-licensed pharmacy. In April 2025, they banned the sale of “counterfeit” semaglutide and tirzepatide.
Compounded medications are not FDA-approved. The agency has identified some areas of concern for compounded GLP-1 drugs including:
- Improper storage during shipping may lead to quality issues.
- Products that contain false information on the product label.
- Dosing concerns with compounded semaglutide and tirzepatide.
- Salt forms should not be used to compound semaglutide.
- Adverse events related to compounded versions of semaglutide and tirzepatide.
- Illegal online sales of these drugs.
- Versions sold falsely for research purposes or not for human consumption.
The agency encourages patients to be vigilant and know the source of their medicine. Carefully check labels of compounded GLP-1 drugs for warning signs such as spelling errors or incorrect addresses and ensure your medicine is provided by a licensed pharmacy and prescribed by a licensed health care provider.
Important Considerations Before Taking Weight Loss Medications
- Consult with a Healthcare Provider: Before starting any weight loss medication, it is crucial to consult with a healthcare provider. They can assess your individual needs, medical history, and potential risks and benefits of each medication.
- Understand Potential Side Effects: All medications have potential side effects. It is important to discuss these with your doctor and understand what to expect.
- Lifestyle Changes are Essential: Weight loss medications are most effective when combined with a healthy eating plan and regular exercise.
- Long-Term Use: Some weight management medications are designed for short-term use, while others are for long-term use. Discuss the duration of treatment with your doctor.
- Cost and Insurance Coverage: Weight loss drugs can be expensive and aren't always paid for by insurance. Check with your insurance provider to understand your coverage options.
- Potential for Weight Regain: Many people gain back some of the weight they lost when they stop taking weight-loss drugs. AOMs may counter the effects of metabolic adaptation and prevent weight regain. After weight reduction, the body metabolically adapts, often causing an increase in hunger hormones and a decrease in satiety hormones and resting metabolic rate, all of which can contribute to weight regain.
The Role of Exercise and Diet
Healthy eating and exercise are the most recommended ways to lose weight. Medications can help with obesity, but they're not a magic bullet. It's also important to remember that no one drug works for all people. While medications may be part of the answer for some, exercise is beneficial for everyone. It's nearly impossible to maintain weight loss without it. Don't get discouraged. Even without losing weight, you can be healthier by being physically active and eating healthy foods. This includes fruits, veggies, whole grains, lean fish, lean meat or tofu, and foods high in calcium.
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