What is semaglutide for weight loss and how does it work?

Whether you've heard about it from a friend or seen it in headlines, semaglutide is becoming a household name. But what exactly is semaglutide, and why has it become so popular for weight loss?

Semaglutide is a prescription medication, more specifically a glucagon-like peptide-1 (GLP-1) receptor agonist. It’s also known as the brand names Ozempic and Wegovy. Ozempic was initially developed and approved by the FDA in 2017 for managing type 2 diabetes. Over time, research showed that semaglutide also helped people lose weight and keep it off, which led to Ozempic being used off-label for weight loss. In 2021, semaglutide received another FDA approval, this time under the brand name Wegovy, for weight management in people with obesity or other weight-related medical conditions. 

This article explores what you need to know about semaglutide, including how it works, who can benefit from it, and the potential risks and challenges that come with it. 

Semaglutide is a GLP-1 receptor agonist medication. Semaglutide is the active ingredient in several brand-name medications, including Ozempic, Wegovy, and Rybelsus. All three contain semaglutide, but each one has different FDA-approved uses, also called indications. They also differ in other ways, such as dosage, strengths, and cost. All three are expensive and have no approved generic alternatives.

Here are some of the key facts to know about each brand: 

*Costs are approximate, based on the list prices of Ozempic, Wegovy, and Rybelsus from Novo Nordisk, the drug manufacturer. Actual costs may be lower, depending on health insurance, discounts, assistance programs, and other factors.

Ozempic and Rybelsus are indicated for improving control of blood glucose (sugar) levels in adults with type 2 diabetes. Ozempic is also approved to help reduce the risk of severe cardiovascular problems, such as heart attacks, in people with type 2 diabetes. You give Ozempic as a once-weekly subcutaneous injection after a healthcare professional teaches you how to inject it. 

Rybelsus, on the other hand, is an oral tablet that you take once a day. It has the same diabetes indication as Ozempic, but Rybelsus isn’t approved for reducing cardiovascular risks. Both Ozempic and Rybelsus are approved for use alongside lifestyle changes including diet and exercise.

Wegovy is approved for weight loss and long-term weight management in adults and children ages 12 years and up with obesity. It’s also approved for this purpose in adults who are overweight and have at least one weight-related health problem. Examples include high blood pressure, high cholesterol, sleep apnea, or type 2 diabetes. 

Previously, Wegovy was approved for people who met specific body mass index (BMI) criteria for having obesity (BMI of 30 or greater) or overweight (BMI of 27 or greater). As of March 2024, Wegovy’s labeling was updated and no longer includes specific BMI criteria. Also as of March 2024, Wegovy was approved to reduce the risk of heart attack or other serious cardiovascular problems in adults with obesity or overweight. Like Ozempic, you inject a dose of Wegovy under the skin once weekly.

If you think semaglutide could benefit your health needs, whether for diabetes management or weight loss, consult with a healthcare provider. They can assess your specific situation, discuss the potential benefits and risks, and determine the most appropriate treatment plan for you.

Regardless of the brand name, semaglutide is thought to work for weight loss by acting on areas of the brain involved in regulating appetite and food intake and slowing the flow of stomach contents on its way to the intestines (known as gastric emptying). These effects of semaglutide may help you feel full faster when you eat and remain satisfied longer after eating. So, using semaglutide can reduce appetite and food cravings, and eating less can lead to weight loss—especially when paired with increased physical activity. 

More specifically, semaglutide works by acting like a natural hormone in your body called GLP-1. Natural GLP-1 is very short-acting in the body, with evidence suggesting it lasts for only one or two minutes. Semaglutide mimics GLP-1, thus enhancing its effects. Scientists are still researching GLP-1 to get a better understanding of its roles in the brain and body. 

While it may seem like GLP-1 drugs became a sensation for weight loss out of the blue, the drug class has been around for a while. The diabetes medication exenatide (Byetta) was the first GLP-1 drug to hit the market in 2005. Since then, this class of medications has grown. Besides semaglutide, examples of other GLP-1 agonists include:

• Dulaglutide (Trulicity)

• Liraglutide (Saxenda, Victoza)

• Lixisenatide (Adlyxin)

• Tirzepatide (Mounjaro, Zepbound), a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist 

Semaglutide has proven to be highly effective for people with type 2 diabetes. Clinical trials have shown meaningful reductions in A1c levels (a marker of average blood sugar) in people taking semaglutide. This can help to prevent complications associated with diabetes, such as cardiovascular disease, neuropathy (nerve damage), and kidney damage.

In one clinical trial, people taking 2 mg of Ozempic per week for type 2 diabetes lost at least 5% and sometimes more than 10% of their body weight after 40 weeks of treatment.

Several clinical studies support semaglutide's efficacy in chronic weight management for people without diabetes. In the trials that led to Wegovy’s approval for weight management, people with obesity or overweight who used 2.4 mg of semaglutide once weekly lost an average of nearly 15% of their body weight over a 68-week treatment period. 

You may wonder if semaglutide stops working over time. So far, evidence points to long-term effectiveness. For instance, a recent analysis of Wegovy trial data shows that semaglutide may provide long-lasting weight loss in people with obesity or overweight. The trial involved adults who used semaglutide for at least four years. Participants had existing cardiovascular disease and a BMI of 27 or higher but did not have diabetes. The results suggest that the medication is effective for weight reduction in people of all genders, ethnicities, and ages—and its effects do not seem to fade over time.

Keep in mind that your experience with semaglutide may vary from that which occurred in clinical trials. For best results, use it as prescribed along with a healthy, balanced diet and increased exercise. 

Does oral semaglutide work for weight loss?

Studies are promising, but oral semaglutide hasn’t been FDA approved for this purpose. Most of the weight loss evidence for semaglutide involves the weekly injection.

In a study published in 2023, researchers tested whether taking oral semaglutide 50 mg daily helps adults with overweight or obesity lose weight compared to a placebo. After 68 weeks, participants on semaglutide lost an average of 15% of their body weight, while those on the placebo lost 2.4%. Higher rates of weight loss (up to 20%) were also seen in the semaglutide group. More side effects occurred with semaglutide, most of which were gastrointestinal issues (80% for semaglutide vs. 46% for placebo).

Note that Rybelsus (semaglutide oral tablet) isn’t currently available in a 50-mg strength, but this could change in the future.

Yes, semaglutide appears to work well for weight loss in people with and without diabetes. Studies of semaglutide 2.4 mg (Wegovy) in adults without diabetes showed a more than 15% body weight reduction. 

Wegovy is approved for adults who have obesity or overweight and have at least one weight-related condition. While diabetes is considered a weight-related condition, you don’t have to be diagnosed with diabetes for semaglutide to be effective for weight loss. 

Like other medications, semaglutide can cause side effects. Common side effects of Ozempic and Wegovy include nausea, vomiting, diarrhea, constipation, and abdominal pain. Temporary discomfort at the injection site can also happen with semaglutide injections.

Gastrointestinal side effects are often mild to moderate, especially during the first few weeks of treatment and after dose increases. Nausea and other digestion-related side effects tend to diminish over time as your body adjusts to the medication. Eating smaller, more frequent meals (instead of three big meals) can help keep nausea at bay. 

Tell your healthcare provider if any side effects feel severe or interfere with your daily routines. They may reduce your dose until you’re feeling better then try again to see how well you tolerate the medication. Some people may need to stop the medication if the side effects continue to bother them. But don’t change or stop the medication on your own; always consult your prescriber before making adjustments. 

Uncommon but serious side effects can include pancreatitis, gallbladder problems, kidney issues if you are dehydrated, hypoglycemia (low blood sugar) if used with certain diabetes medications, and allergic reactions. Other side effects are possible.

Semaglutide is not right for everyone. Ozempic and other GLP-1 agonist medications carry a boxed warning on their labeling about the risk of thyroid c-cell tumors. People with a personal or family history of medullary thyroid carcinoma (a type of thyroid cancer) or multiple endocrine neoplasia syndrome type 2 (a genetic condition that increases the risk of thyroid tumors) shouldn’t use semaglutide. 

Healthcare providers do not recommend semaglutide for people with a history of pancreatitis or allergic reactions to semaglutide. Semaglutide also isn’t recommended while pregnant or breastfeeding, and the medication should be stopped at least 2 months before trying to conceive.  

Using more than one semaglutide product at a time is also not recommended. 

Tell your healthcare provider about any health conditions you have as well as everything you take, including prescription drugs, over-the-counter medications, herbs and supplements. 

Compounded semaglutide is a version of the medication made by a compounding pharmacy. Compounding pharmacies make customized drugs by mixing or altering ingredients to meet specific patient needs. This approach is useful if you need a dose or form that's not available commercially or if there's a shortage of FDA-approved drugs. Compounded semaglutide can be an option for you if your insurance doesn’t cover semaglutide for weight loss or you’re struggling to find the brand name versions in stock. 

Compounded drugs are not subject to FDA approval and do not have to undergo manufacturing, effectiveness, or safety review. Compounded medications aren't regulated like commercially manufactured drugs, so their quality and potency can vary. Always consult your healthcare provider before using compounded semaglutide. 

While compounded drugs don't need FDA approval or undergo the same safety and effectiveness reviews, they must still comply with federal laws and meet FDA and state quality standards.

Bottom line: If you're thinking about using semaglutide for weight loss, it's important to talk to your doctor or connect with a provider online at Ro. They can help you understand the benefits and risks and decide if semaglutide or another weight loss medication is right for you.

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How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

July 17, 2024

Written by

Patricia Weiser, PharmD

Fact checked by

Beverly Tchang, MD

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About the medical reviewer

Beverly Tchang, MD

Beverly Tchang, MD, is an Obesity Medicine Advisor for Ro. She is also an assistant professor of Clinical Medicine at Weill Cornell Medicine in New York and triple board-certified in Internal Medicine, Endocrinology, and Obesity Medicine.