Comparing Oral vs. Injectable Semaglutide

Key takeaways

Semaglutide is a medication that can support weight loss. It’s available as both oral tablets and injections. The oral form offers a needle-free option but typically needs to be taken every day, while injections are usually administered weekly.

Many people know semaglutide for its injectable forms, like Ozempic^® and Wegovy^®, but the oral version, Rybelsus^®, works similarly and can be an alternative for some people.

Let’s break down the differences between oral versus injectable semaglutide for weight loss, including effectiveness, dosing, and side effects, so you can see which option may fit your needs.

Semaglutide is the active ingredient in the injectable type 2 diabetes medication Ozempic^® and the weight loss medication Wegovy^®.

It’s a glucagon-like peptide-1 receptor agonist (or GLP-1 RA) that works by mimicking the GLP-1 hormone, which is naturally produced in the gut.

According to the pharmaceutical manufacturer Novo Nordisk and the FDA’s drug insert for Wegovy^®, injectable semaglutide has several effects on the body, including:

• Managing blood sugar levels. It increases insulin production and releases it into the bloodstream to help lower blood sugar (glucose) when it is high.

• Regulating appetite. It interacts with parts of the brain to reduce appetite and signal to the body that you’re full.

• Helping you eat less. By slowing how quickly food moves through the stomach, it can help you feel full sooner and stay full longer, leading to reduced calorie intake.

• Lose weight and keep it off. When used along with a reduced-calorie diet and increased physical activity, Wegovy^® has been shown to support long-term weight loss and weight maintenance.

The U.S. Food and Drug Administration (FDA) has approved three products containing semaglutide, all made by Novo Nordisk. While the active ingredient is the same, Rybelsus^® comes as an oral tablet, and Ozempic^® and Wegovy^® are injectable.

Here’s what to know about taking semaglutide as a tablet versus an injection for weight loss.

Rybelsus^®

Rybelsus^® is FDA-approved to treat type 2 diabetes. It’s meant to be used alongside a nutrition plan and regular physical activity to manage blood sugar levels.

This drug doesn’t have FDA approval for weight loss, but some providers prescribe Rybelsus^® off-label for this purpose. (Off-label use is when a medication is prescribed to treat a condition it’s not FDA-approved for — in this case, overweight or obesity.)

Ozempic^®

Like Rybelsus^®, Ozempic^® injections are FDA-approved for people with type 2 diabetes. This medication is meant to be used with healthy eating habits and exercise to improve blood sugar levels.

Ozempic^® also has FDA approval to help prevent major cardiovascular events like stroke or heart attack in folks with diabetes who also have heart disease. Ozempic^® is sometimes prescribed off-label for weight loss, too.

Wegovy^®

Wegovy^® is a once-weekly semaglutide injection that’s FDA-approved to be used alongside healthy eating and exercise to treat obesity.

This medication may also be prescribed to people with an overweight BMI (body mass index) who have a weight-related condition, such as high blood pressure (hypertension), heart disease, or sleep apnea.

Semaglutide Tablets vs. Injections: Pros and Cons

According to Craig Primack, MD, a physician specializing in obesity medicine and the Senior Vice President of Weight Loss at Hims & Hers, “Patients taking injectable semaglutide typically lose more weight than those on oral semaglutide.”

The reason for this, Dr. Primack explains, “is because the dose of the injectable form achieves higher blood levels and, therefore, better appetite control.”

Does oral semaglutide work? Short answer: Oral semaglutide may not be as effective as injectable semaglutide for weight loss.

While both versions typically help people lose weight, injectable semaglutide may lead to more significant weight loss. But both oral and injectable semaglutide help effectively lower blood sugar levels.

Research on Oral vs. Injectable Semaglutide

Research sponsored by Novo Nordisk in patients with type 2 diabetes found that:

• Together with diet and exercise, Ozempic^® led to an average weight loss of almost 10 pounds (in those with diabetes)

• Rybelsus^® led to an average weight loss of over eight pounds

It’s important to note, though, that these trials involved lower doses of semaglutide (Ozempic^®) than those sometimes used to treat obesity.

In clinical trials of Wegovy^®, which included a higher dose of injectable semaglutide (2.4 mg), people lost an average of almost 15 percent of their body weight.

The bottom line: When it comes to oral semaglutide versus injectable, the latter may be more effective for weight loss.

Rybelsus^® is the current oral formulation of semaglutide, but additional semaglutide tablets may be available in the future. Here’s what we know.

Novo Nordisk has been studying a high-dose form of semaglutide that can be taken by mouth specifically for weight loss.

The company previously announced that clinical trial participants lost an average of 17.4 percent of their baseline body weight after 68 weeks of using this new oral formulation. Those who took a placebo lost only 1.8 percent of their baseline body weight.

The most common side effects of both oral semaglutide and injectable semaglutide impact the gastrointestinal system. They can include:

• Nausea

• Vomiting

• Constipation

• Diarrhea

• Upset stomach

• Heartburn (acid reflux)

If you’re trying to decide between the oral form of semaglutide and injectable semaglutide, you may be wondering if one leads to a higher frequency of side effects or more intense adverse effects.

Research on this topic is scarce so far, but right now, there appears to be no difference between the two.

A 2024 Novo Nordisk-funded study found that there wasn’t a significant difference in the number of people reporting side effects for each form of semaglutide.

Oral semaglutide weight loss medication (that is, the diabetes medication prescribed off-label for weight loss) is taken once daily by mouth. Seems pretty simple, right?

However, there’s actually a bit of nuance to be aware of. The prescribing information for Rybelsus^® also says to:

• Take it when you first wake up, before eating or drinking anything, while you still have an empty stomach

• Swallow each tablet whole, using only a small sip of water (four ounces or less)

• Wait 30 minutes before having additional liquids, food, or other oral medications

When in doubt, go with your healthcare provider’s instructions and reach out to them if you’re ever unsure how to take your medication.

Injectable semaglutide is taken once weekly. It’s given as a subcutaneous injection. This means it’s injected into the layer of fatty tissue that lies just under the skin (not into a vein or muscle).

If you’re unsure about how to take semaglutide for weight loss or diabetes, don’t worry. A healthcare provider will walk you through the steps before it’s time to do it yourself.

There are a few injection sites you can use to inject subcutaneous semaglutide:

• Abdomen

• Thigh

• Upper arm

It’s perfectly normal to have concerns about pain during or after an injection. If that’s you, some research suggests that subcutaneous injections in the abdomen (a few inches to either side of the belly button) are less painful than those given in the thigh.

The prescribing information for both Ozempic^® and Wegovy^® has additional injection instructions:

• Do your injection on the same day each week. That said, you can do your injection any time that day.

• It’s possible to change your injection day as long as your last injection was at least two days ago. But check with your healthcare provider first.

• Don’t use the exact same injection site for each dose. Be sure to regularly rotate your injection site to avoid irritation or bruising.

• Your injection can be done with or without food.

Learn more about how to inject semaglutide in our guide.

There is no one-size-fits-all answer for which form of semaglutide is best. The version a medical provider recommends can depend on its use.

Here’s what to keep in mind about oral versus injectable semaglutide:

• Rybelsus^® is currently the only brand-name version of oral semaglutide. Ozempic^® and Wegovy^® are the brands for the injectable form of semaglutide.

• Wegovy^® is currently the only semaglutide product FDA-approved specifically for weight management, while other semaglutide medications may be prescribed off-label for weight loss.

• Personal preference can also play a role in figuring out the best medication. Some folks might be perfectly okay doing once-weekly injections, but the idea of self-administering an injection may not appeal to others. If you’d rather swallow pills, semaglutide tablets might be the way to go. If not, there are other oral weight loss medications.

Whichever way you’re leaning for this GLP-1 receptor agonist medication (or another weight loss drug), your first step is connecting with a healthcare professional.

Through Hers, you can connect with a licensed healthcare provider who can evaluate your health profile and needs, then let you know if you’re a good candidate for weight loss medications. If eligible, you can access a range of weight loss treatments, including oral medications and injections.