How does semaglutide work?

What do Ozempic, Wegovy, and Rybelsus all have in common? Semaglutide, for one. 

Semaglutide is the active ingredient in all three brand-name prescription drugs, all of which are glucagon-like peptide 1 (GLP-1) receptor agonists. GLP-1 drugs have become popular because of their effectiveness for weight loss. 

Semaglutide is structurally similar to GLP-1, a natural hormone involved in regulating appetite and blood sugar levels. Semaglutide works by binding to the same receptors as GLP-1, which stimulates insulin release. This results in lower blood sugar levels. 

The drug also works by slowing stomach emptying (the part of digestion that moves stomach contents into the intestines), causing a feeling of fullness and reduced desire to eat. As a result, taking semaglutide leads to improved control of type 2 diabetes and weight loss, especially when paired with a healthy diet and physical activity.

It may seem confusing that three different brand-name medications can contain the same active ingredient (semaglutide), but each one is approved by the Food and Drug Administration (FDA) for unique purposes:

• Ozempic, a weekly injection, has FDA approval for controlling blood sugar as well as reducing the risk of serious cardiovascular problems (like heart attack) in adults with type 2 diabetes mellitus. 

• Wegovy, also a weekly injection, is FDA-approved for weight management alongside diet and exercise in obese or overweight individuals.

• Rybelsus has FDA approval for controlling blood sugar levels in adults with type 2 diabetes. It’s distinct from the other semaglutide-containing medications because Rybelsus comes as an oral tablet, not an injectable solution. 

Keep reading to learn more about semaglutide, its uses, potential side effects, and a more in-depth look at how it works for weight loss and diabetes. 

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The FDA initially approved semaglutide under the brand name Ozempic in 2017 for managing type 2 diabetes. Since then, semaglutide has been approved under two other brand names and for additional indications, including weight loss.

What is Ozempic? Is semaglutide the same as Ozempic?

Ozempic (semaglutide) is a GLP-1 receptor agonist. It is an injectable solution given by subcutaneous injection (administered just under the skin). You can inject Ozempic at one of three optional injection sites: abdomen, thigh, or back of the upper arm. A healthcare professional will show you how to inject Ozempic. 

Specifically, the FDA has approved Ozempic for the following uses:

• To improve control over blood sugar levels in adults (18 years or older) with type 2 diabetes mellitus, in combination with lifestyle changes of diet and increased exercise. 

• To reduce the risk of cardiovascular events (such as heart attack or stroke) in adults diagnosed with both type 2 diabetes mellitus and heart disease.

Ozempic is given once a week. The starting dose is 0.25 milligrams once weekly. Then, your healthcare provider will slowly increase your dose each month until you reach the desired level of blood sugar control. Your healthcare provider can guide you on the goal range for your blood sugar levels and A1C. The typical maintenance (ongoing) dosage of Ozempic is 1 mg once weekly. The drug is usually prescribed for long-term treatment, assuming it continues to be safe and effective for you. 

What is Wegovy?

Wegovy (semaglutide) is similar to Ozempic in several ways. In fact, it is the same active ingredient, sold under a different brand name. It also belongs to the GLP-1 receptor agonist class and, like Ozempic, Wegovy requires a once-a-week injection under the skin. Here is how to inject Wegovy.

However, the FDA approves Wegovy for different uses than Ozempic. Along with a reduced-calorie diet and more exercise, Wegovy is indicated for chronic weight management in certain people, including:

• Adults with an initial body mass index (BMI) of 30 kg/m², which qualifies as obesity.

• Adults with an initial BMI of 27 kg/m², which qualifies as overweight, who also have at least one weight-related medical condition, such as:

  • High blood pressure,

  • Type 2 diabetes, or

  • High cholesterol.

• Children or adolescents ages 12 to 17 years old with an initial BMI that is greater than the 95th percentile, based on their age and biological sex.

Wegovy dosing starts at 0.25 mg once weekly. Like Ozempic, the dosage of Wegovy starts low and the healthcare provider gradually increases it every four weeks, according to individual tolerability. The long-term maintenance dosage of Wegovy is either 1.7 mg or 2.4 mg once weekly, depending on individual factors.

What is Rybelsus?

Rybelsus (semaglutide) is another GLP-1 receptor agonist in the same drug class as Ozempic and Wegovy. The main difference between Rybelsus and the other semaglutide products is how you take it; while Ozempic and Wegovy require a once-weekly injection, Rybelsus comes as a tablet, taken by mouth. The FDA approves Rybelsus to improve control of blood sugar levels in adults with type 2 diabetes in addition to lifestyle changes of diet and exercise.

Rybelsus is a once-daily pill. The typical starting dose is one 3-mg tablet taken once daily for the first 30 days. Then, the dose is usually increased to one 7-mg tablet once daily for the next 30 days. Depending on individual response, healthcare providers may further increase the dosage of Rybelsus up to the maximum dose of 14 mg once daily.

Note that the timing of Rybelsus matters. You should take Rybelsus 30 minutes before your first food, drink, or other oral medications of the day. Take Rybelsus with plain water only, but no more than 4 ounces. Not following these instructions can make Rybelsus less effective or more likely to cause side effects. In addition, you should swallow Rybelsus tablets whole. Do not cut, crush, or chew them.

Here is a more detailed look at how semaglutide works for weight loss, diabetes, and reducing cardiovascular risks. 

Semaglutide for diabetes

Glucagon-like peptide-1 (GLP-1) is a natural hormone in the human body. Normally, this hormone works in response to sugar in the blood, which occurs after eating or drinking. GLP-1 reacts to higher blood sugar levels by binding to the GLP-1 receptor and stimulating the release of insulin from the pancreas. (Insulin is another natural hormone responsible for moving sugar from the blood into cells, which energizes cells and lowers blood sugar levels.) However, in people with type 2 diabetes, the effects of natural GLP-1 are drastically reduced or, in some cases, non-existent.

GLP-1 receptor agonists drugs are also known as GLP-1 analogs. They work by mimicking the natural GLP-1 hormone. Since semaglutide is similar to this hormone, it can bind to the GLP-1 receptor, too. This boosts the effects of GLP-1, resulting in insulin release and a subsequent reduction in blood sugar.

Additionally, semaglutide stops the pancreas from making too much glucagon when blood sugar is high. Glucagon is a stored form of blood sugar, so preventing its overproduction helps control diabetes. Keeping diabetes under control by maintaining blood sugar levels within a healthy range is essential for preventing complications of diabetes. 

Semaglutide for Reducing Cardiovascular Risk

Heart disease commonly develops in people with type 2 diabetes, resulting in a higher risk of dangerous cardiovascular problems, including heart attack or stroke. In addition to semaglutide’s role in reducing blood sugar, the medication results in a number of beneficial and protective actions on the heart. 

Overall, the effects of semaglutide may lead to improved heart health. A 2023 study found a 20% cardiovascular risk reduction for obese individuals taking semaglutide compared to those not taking a GLP-1 drug.

Elevated blood pressure and high cholesterol both increase the risk of having a heart attack or stroke. Semaglutide and other GLP-1 receptor agonists have been shown to help lower blood pressure and reduce overall cholesterol levels. Regarding heart health, GLP-1 agonists can also help the heart pump better, improve blood flow to the heart, and decrease the risk of heart-related problems.

GLP-1s may also offer protective effects on the heart. In animal studies, mice given GLP-1 analogs after a heart attack experienced better outcomes than mice without GLP-1 analog exposure. Additionally, semaglutide may help protect heart cells known as cardiomyocytes by preventing cell death and increasing sugar metabolism in these cells.

Semaglutide for Weight Loss

Semaglutide promotes weight loss by altering your body’s appetite and satiety (feeling full) regulation. Following a meal, semaglutide delays stomach emptying, slowing the rate at which food progresses through digestion. This keeps the stomach fuller for longer, likely reducing the desire to eat between meals. Additionally, semaglutide is associated with enhanced satiety or feeling of fullness. As a result, you may eat less during meals, leading to weight loss. 

In fact, semaglutide may lead to significant weight loss when used along with a reduced-calorie diet and enhanced exercise plans. In a study comparing the impact of lifestyle changes with and without semaglutide, those taking semaglutide lost 16% of their initial body weight over 16 months—an average of nearly 38 pounds. While weight loss of 15% or more may be achieved by about half of individuals using semaglutide for a year or longer, most people can generally expect a loss of 5% body weight within three months of starting the drug.

Other potential benefits of semaglutide

Although more research is necessary for confirmation, early studies suggest additional potential health benefits of semaglutide. For example, in studies of Alzheimer’s disease in animal models, semaglutide has been shown to decrease some early signs of the disease and enhance memory. Similarly, some research suggests that GLP-1 agonists may reduce the risk of cancer in people with type 2 diabetes and/or obesity. 

Semaglutide is associated with a number of common side effects, including:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Abdominal pain

• Pain or itching at the injection site (with Ozempic or Wegovy)

Generally, the digestion-related side effects occur more frequently when you first start or after your dose has been recently increased. In most cases, nausea and other digestive side effects disappear as your body adjusts to the medication. If side effects persist or seem severe, tell your healthcare provider. They may temporarily reduce your dose or recommend other ways to manage these side effects.

While uncommon, serious side effects have been reported with semaglutide. These include:

• Pancreatitis (inflammation of the pancreas)

• Severe allergic reaction

• Gallbladder disease

• Kidney problems

• Increased risk of a vision problem diabetic retinopathy 

• Dangerously low blood sugar when taken with certain diabetes medications, such as insulin injections 

If these side effects occur, seek medical attention or contact your provider for personalized medical advice.

Important warning

The FDA requires semaglutide and all GLP-1 receptor agonist drugs to carry a boxed warning due to the potential risk of thyroid tumors. In animal studies, semaglutide caused a type of thyroid cancer known as thyroid c-cell tumors in mice and rats. It remains unclear if semaglutide leads to similar thyroid tumors in humans. As a precaution, semaglutide is not recommended for people with a personal or family history of medullary thyroid cancer or individuals with multiple endocrine neoplasia syndrome 2 (MEN2).

Semaglutide carries other warnings and precautions. A healthcare provider can determine if semaglutide is a safe option 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

November 21, 2023

Written by

Patricia Weiser, PharmD

Fact checked by

Felix Gussone, MD

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About the medical reviewer

Felix Gussone, MD, Ro

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.