The pharmacological treatment of obesity is rapidly evolving. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a significant player in weight management, gaining popularity and media attention in recent years. Sold under the brand name Wegovy, it has been approved by the FDA for chronic weight management 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. Initially used to treat type 2 diabetes (under the name Ozempic), semaglutide mimics hormones released when we eat, triggering insulin production and a feeling of fullness.
How Semaglutide Works
Semaglutide belongs to a class of medications known as glucagon-like peptide-1 receptor agonists, or GLP-1 RAs. It mimics the GLP-1 hormone, released in the gut in response to eating. One role of GLP-1 is to prompt the body to produce more insulin, which reduces blood sugar (glucose). But GLP-1 in higher amounts also interacts with the parts of the brain that suppress your appetite and signal you to feel full. The bioavailability of semaglutide is 89% when injected subcutaneously and will be present for approximately 5-7 weeks after the last dose. It is eliminated via the urine and feces and can be administered subcutaneously without regard to meals.
Who is a Candidate for Semaglutide?
Determining whether someone is a candidate for weight loss medications begins with BMI. The guidelines for tirzepatide (Zepbound) and semaglutide (Wegovy) state that a patient should have a BMI of 30 or a BMI of 27 with weight-related health problems. The FDA recommends Wegovy for weight loss if you meet one of the following criteria:
- Have a body mass index (BMI) of 27kg/m2 or greater and at least one weight-related condition, such as high blood pressure, Type 2 diabetes, or high cholesterol.
- Have a BMI of 30kg/m2 or greater.
For each individual case, the doctor and patient should discuss the patient’s current health issues, other medications, and family medical history.
Dosage and Administration
The dose of Wegovy 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. Semaglutide is administered as an injection once weekly. Administration sites include the abdomen, thigh, and upper arm. The dosing for some of these includes a long ramp-up period-up to five months-to reach full dosage.
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Effectiveness of Semaglutide
Semaglutide performs on a new level. An early study of 2,000 obese adults compared people using semaglutide plus a diet and exercise program with people who made the same lifestyle changes without semaglutide. After 68 weeks, half of the participants using semaglutide lost 15% of their body weight, and nearly a third lost 20%. Participants who incorporated only lifestyle changes lost about 2.4% of their weight.
- STEP 1 Trial: Demonstrated a significant reduction in body weight when compared with either placebo or liraglutide.
- -14.9% with semaglutide 2.4 mg vs. -2.4% with placebo
- 86.4% of patients treated with semaglutide 2.4 mg vs. 31.5% with placebo achieved a weight loss of 5% or more at 68 weeks.
- 68.8% of patients treated with semaglutide 2.4 mg vs. 12% with placebo achieved a weight loss of 10% or more at 68 weeks.
- STEP 4 Trial:
- -17.4% with continued semaglutide vs. -15.2% with semaglutide vs. placebo
- 77.1% of patients treated with semaglutide vs. 34.4% with placebo achieved a weight loss of 5% or more at 68 weeks.
- Across STEP trials to date, patients experienced clinically significant weight loss.
Benefits Beyond Weight Loss
Semaglutide offers benefits beyond just weight reduction. A 2023 study in the New England Journal of Medicine found that semaglutide reduced the risk of death from heart disease and nonfatal heart attacks or strokes by about 20 percent for people who were obese or overweight. Studies show improvements in cardiovascular risk factors and metabolic markers.
Potential Side Effects
The side effects of semaglutide are typically mild - especially when compared to the complications associated with overweight and obesity. People taking semaglutide for weight loss may experience:
- Dizziness
- Fatigue
- Gastrointestinal issues, such as diarrhea, constipation, and gassiness
- Headache
- Stomach issues, including nausea, vomiting, pain, or distension (bloat)
Gastrointestinal issues are the most common complaint among people just starting semaglutide. But you may be able to reduce the side effects by beginning on a lower dose and then slowly increasing the amount you take. Try for frequent small meals. That can help to minimize the side effects of these drugs, which can include nausea and an upset stomach.
Precautions and Contraindications
Avoid semaglutide if you have:
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- History of medullary thyroid cancer
- History of gallbladder disease
- History of pancreatitis
- Multiple endocrine neoplasia syndrome type 2 (MEN2)
It's also important to note the potential for muscle loss with weight loss medications. Be active. The more you exercise, the more likely you can offset muscle loss from these weight loss drugs. Get enough protein. This also helps prevent muscle loss. Aim for at least 1.2 grams of protein for each kilogram of body weight.
The Cost Factor
GLP-1s are notoriously costly. The Kaiser Family Foundation estimates the annual net price of Wegovy at $13,600 and are not covered by insurance. Insurance coverage varies and will affect many patients’ choices about going on weight loss medications. Medicare Part D won’t cover weight loss drugs-which can run about $1,300 a month out of pocket-solely for weight loss. But Part D will generally cover them as a treatment for type 2 diabetes.
The Rise of Compounded Semaglutide
With the growing demand for weight-loss drugs like Wegovy, new online companies seem to pop up every day, offering telehealth prescribing of cheaper, compounded versions of the medicines. And for some patients, they offer a reprieve from the high name-brand prices, insurance company coverage denials, and drug shortages. The convenience and cost can be appealing, but there are some risks.
Compounding pharmacies exist to help patients whose needs aren’t met by existing approved drugs. The compounded drugs are not generics, nor do they go through the Food and Drug Administration’s approval process. Instead, compounding pharmacists tailor drugs for individual patients who need them and are mostly regulated on the state level by boards of pharmacy. For instance, if a drug is only available as a pill but an elderly patient can’t swallow one, a doctor would write a prescription so that a compounding pharmacist could prepare it in liquid form. Compounding pharmacists are not supposed to make what are “essentially” copies of commercially available approved drugs, according to the FDA. But sometimes, compounding pharmacies can legally pitch in during a drug shortage. That’s what’s happening now.
Concerns with Compounded Versions of These Drugs
A compounded drug might be appropriate if a patient’s medical need cannot be met by an FDA-approved drug, or the FDA-approved drug is not commercially available. However, compounded drugs are not FDA approved. This means the agency does not review compounded drugs for safety, effectiveness or quality before they are marketed. The agency has identified some areas of concern for compounded GLP-1 drugs.
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- Improper storage during shipping: Injectable GLP-1 drugs require refrigeration as indicated in their package inserts. FDA has received complaints that certain compounded GLP-1 drugs have arrived warm or with inadequate ice packs to keep the drug at recommended storage temperatures.
- Products that contain false information on the product label: In some cases, the compounding pharmacies identified on the labels of the products do not exist. In other cases, the labels of the fraudulent compounded medicine contain the name of a licensed pharmacy that, based on information FDA has gathered, did not compound these products.FDA is aware of one reported adverse event associated with a product labeled as compounded tirzepatide from a pharmacy that did not actually compound the product. The adverse event report included symptoms such as redness, site swelling, pain, and a red lump at the injection site.
- Dosing concerns: FDA received multiple reports of adverse events, some requiring hospitalization, that may be related to dosing errors associated with compounded injectable semaglutide products. These dosing errors resulted from patients measuring and self-administering incorrect doses of the drug, and in some cases, health care professionals miscalculating doses of the drug. Additionally, the agency has received adverse event reports that may be related to patients prescribed compounded semaglutide or tirzepatide products in doses beyond what is in the FDA-approved drug label. This could mean using more product in a single dose, taking doses more frequently or increasing the amount more quickly (titration schedule). Some of the adverse events are serious and some patients reported seeking medical attention for their symptoms, including nausea, vomiting, diarrhea, abdominal pain and constipation.
- Salt forms should not be used to compound semaglutide: The agency is aware that some semaglutide products sold by compounders may be the salt forms. These salt forms, including semaglutide sodium and semaglutide acetate, are different active ingredients than are used in the approved drugs. The agency does not have information on whether these salts have the same chemical and pharmacologic properties as the active ingredient in the approved drug, and we are not aware of any lawful basis for their use in compounding.
- Retatrutide and cagrilintide cannot be used in compounding
Recommendations for Consumers Considering Compounded Semaglutide
- Patients should obtain a prescription from their doctor and fill the prescription at a state-licensed pharmacy. Visit FDA’s BeSafeRx campaign for resources to safely buy prescription medicines online. Talk to your doctor if you have questions about your medicines.
- 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.
- If you receive a product with a licensed pharmacy name on the label that you think might be fraudulent, contact the pharmacy to ask if it is their product.
- One thing consumers can do to protect themselves is check that their pharmacy is licensed in their state, says Brunner. The FDA has a handy page of state-by-state links. You can also ask the compounding pharmacist where they get their semaglutide, and check this FDA database online to see if that factory is registered with the FDA.
- Licenses and registrations like this mean the facilities can be inspected and need to comply with safety and quality standards.
- If you see anyone advertising compounded “Ozempic” or “Wegovy” instead of compounded semaglutide, it’s a red flag, Brunner says. Compounders aren’t legally allowed to use the name brand in their marketing.
What to Discuss with Your Doctor
If you’re considering semaglutide for weight loss, your first step should be consulting your primary care physician (PCP). They know your personal and family medical history and can guide you in the best treatment for your condition. Unlike online providers who don’t get to know you (and your medical records) in person, your primary care provider can monitor other health issues that might complicate things. Patients on insulin, for instance, might need a lower dose as they shed pounds while using semaglutide. Too much insulin can be dangerous and lead to seizures or even death. It’s also important to physically check a patient’s thyroid because the drug - brand name or compounded - has a rare side effect: thyroid cancer.
Alternatives to Semaglutide
It can be easy to overlook first-generation AOMs, but these may be appropriate for some patients, especially when cost is a factor. Other FDA-approved medications for chronic weight management include:
- Liraglutide (Saxenda, Victoza): 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.
- Phentermine: 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.
- Topiramate: Can be combined with phentermine to decrease appetite and cravings.
- Naltrexone-bupropion (Contrave): Combines an opioid receptor antagonist with an antidepressant to affect the pleasure-reward areas of the brain and thereby decrease cravings and appetite.
- Orlistat (Xenical, Alli): A lipase inhibitor that comes in a capsule. Undigested fat is then passed through the body. An over-the-counter formulation is available at 60 mg capsules with each fat-containing meal.
- Setmelanotide: 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.
- Plenity: A medical device rather than a medication, 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.
- Zepbound (tirzepatide): It is both a GLP-1 and a GIP receptor agonist. Like semaglutide, it works by reducing appetite and is meant to be used in combination with diet and exercise to lose weight.
The Future of Weight Loss Medications
With fervent 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).