Oral vs. Injectable Semaglutide: Effectiveness & Side Effects

Key Takeaways:

• You can get semaglutide injections (Ozempic^® and Wegovy^®) and oral semaglutide (Rybelsus^®).

• Injections are usually more effective for weight loss than pills.

• If you don’t like needles, Rybelsus^® could be a good option. There are also other oral weight loss medications.

Semaglutide (Ozempic^®, Wegovy^®, Rybelsus^®) comes in both injection and oral form. But beyond how you take it, what’s the difference? And which form is more effective for weight loss?

Semaglutide injections and semaglutide pills work in similar ways, but injections are usually more effective for weight loss than pills.

We’ll explore oral vs. injectable semaglutide in more detail to help you figure out the right option for you.

So far, the Food and Drug Administration (FDA) has approved three semaglutide medications. Those include:

• Ozempic^®

• Wegovy^®

• Rybelsus^®

Let’s take a closer look at these oral and injectable forms of semaglutide.

Ozempic^®

Ozempic^® is FDA-approved to help people with type 2 diabetes control their blood sugar. It’s sometimes prescribed off-label for weight loss in people with overweight and obesity.

It’s a once-a-week injection you take alongside making lifestyle changes, like eating more whole foods and doing more daily movement.

As well as type 2 diabetes, Ozempic^® is FDA-approved to reduce the risk of major cardiovascular events — like stroke and heart attack — in people with type 2 diabetes and cardiovascular disease.

It’s also approved to reduce cardiovascular death and kidney risks in those with type 2 diabetes and chronic kidney disease.

Wegovy^®

Wegovy^® is also a once-a-week injection. It contains a higher dose of semaglutide than Ozempic^®, and it’s currently the only semaglutide medication FDA-approved for weight loss.

This drug is FDA-approved for weight reduction and chronic weight management alongside diet and exercise changes. It’s for people with obesity or overweight with at least one weight-related health condition, like:

• High blood pressure (hypertension)

• High cholesterol (dyslipidemia)

• Type 2 diabetes

• Sleep apnea

Wegovy^® is also approved to reduce cardiovascular risks in those with cardiovascular disease and either obesity or overweight. It can also be prescribed to treat a type of fatty liver disease called noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH).

→ Learn more: Ozempic^® vs. Wegovy^®

Rybelsus^®

Rybelsus^® is a daily semaglutide pill. Alongside eating more nutritious foods and doing more movement, it’s prescribed for people with type 2 diabetes to help manage their blood sugar.

Like Ozempic^®, healthcare professionals sometimes prescribe Rybelsus^® off-label for weight loss when appropriate.

Oral semaglutide may not be as effective as injectable semaglutide. Both formulations of semaglutide can help promote weight loss, but semaglutide injections can lead to more weight loss than oral semaglutide.

Research on Oral vs. Injectable Semaglutide

Research from 2021 looked at people with type 2 diabetes who made diet and exercise changes and took either 1 mg (milligram) of Ozempic^® or 14 mg of Rybelsus^®.

Here’s what the results found:

• People taking Ozempic^® lost about 10 pounds.

• People taking Rybelsus^® lost roughly 8 pounds.

Wegovy^® contains a higher dose of semaglutide than Ozempic^® and may be even more effective for weight loss.

One Wegovy^® study found that those taking a 2.4-mg dose lost an average of around 15 percent of their body weight over 68 weeks.

Results are similar out in the real world.

“In my experience, patients taking injectable semaglutide typically lose more weight than those on oral semaglutide,” says Craig Primack, MD, a physician specializing in obesity medicine and senior vice president of weight management at Hims & Hers.

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

The side effects of oral semaglutide and semaglutide injections are mostly the same.

Semaglutide side effects include:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Stomach pain

You may feel side effects when you first start taking semaglutide and when your dose increases. But you should start feeling better with time as your body adjusts.

Besides having similar side effects, both oral and injectable semaglutide may cause side effects for a similar number of people — although research is mixed.

A 2024 study on people with type 2 diabetes compared Ozempic^® with Rybelsus^®. The number of people who experienced side effects was similar.

However, another study from 2024 on people with type 2 diabetes found that side effects were more common in people taking oral semaglutide than semaglutide injections.

You take oral semaglutide once a day by mouth. There are a few other important points to know about taking this medication.

Here’s how you take Rybelsus^®:

• Take Rybelsus^® in the morning, at least 30 minutes before any food, drinks, or other oral medications or supplements.

• Take it with no more than 4 ounces of plain water.

• Swallow the tablet whole — don’t crush, chew, or split it.

Your prescribing healthcare provider can give you any further instructions you need to follow.

To take injectable semaglutide, you’ll give yourself a shot once a week. Ideally, you’ll do this on the same day each week. But you can inject it at any time, with or without food.

Semaglutide is a subcutaneous injection, meaning you inject the medication just under your skin — not into a vein or muscle. You’ll use a tiny needle that many people don’t even feel.

You can inject semaglutide into your:

• Stomach

• Thigh

• Upper arm

Rotate your injection site each week. You can inject into the same area, but not the exact same spot.

Need to change your injection day? You can do this as long as you gave yourself your last injection at least two days before. Check with your provider to be sure.

Your healthcare provider can also explain how to give yourself a semaglutide injection. It can sound daunting, but once you get the hang of it, it’s quick, easy, and pretty painless.

Currently, Rybelsus^® is the only oral form of semaglutide, but more oral semaglutide medications could hit the market in the future.

Novo Nordisk (the manufacturer of Ozempic^®, Wegovy^®, and Rybelsus^®) is studying a high-dose oral form of semaglutide for weight loss.

Clinical trials found that people taking 50 mg of oral semaglutide lost an average of 17.4 percent of their body weight in 68 weeks.

More research is needed to check safety and efficacy.

Both oral and injectable semaglutide can help you achieve your weight loss goals. But the best medication for you depends on a whole host of factors.

Here’s what to know:

• Ozempic^® and Wegovy^® are semaglutide injections, whereas Rybelsus^® is a semaglutide pill.

• All forms of semaglutide can help you lose weight, but semaglutide injections are generally more effective than semaglutide pills.

• The best form of semaglutide for you depends on your health conditions, your feelings about needs, and whether you’d prefer a daily or weekly treatment. Cost and availability might also come into play.

A healthcare provider can help you decide between oral vs. injectable semaglutide — as well as semaglutide vs. other weight loss drugs, like metformin and topiramate.

To get started, take our free online weight loss assessment. A licensed healthcare provider will go over your answers and let you know if you’re eligible for weight loss medications.

Check out answers to frequently asked questions about oral vs. injectable semaglutide.

What is semaglutide and what does it do?

Semaglutide is a glucagon-like peptide-1 receptor agonist, or GLP-1. It’s FDA-approved for type 2 diabetes under the brand names Ozempic^® and Rybelsus^®. Under the brand name Wegovy^®, it’s FDA-approved for weight loss in people with overweight and obesity.

For weight loss, Wegovy^® works by reducing hunger, making you feel fuller, and curbing food cravings. These effects can help you eat more nutritious foods and avoid overeating, encouraging weight loss. Besides initial weight loss, semaglutide can help you maintain weight loss in the long run.

How often do you take oral vs. injectable semaglutide?

You take oral semaglutide once a day and injectable semaglutide once a week.

What are the disadvantages of oral semaglutide?

Some disadvantages of oral semaglutide:

• You might not lose as much weight compared to injectable semaglutide.

• You might experience more side effects compared to injectable semaglutide.

• You have it take a tablet every day, rather than an injection once a week.

• You have to take it on an empty stomach, 30 minutes before food and drinks.

Can you switch from injectable semaglutide to oral semaglutide?

You can switch from injectable semaglutide to oral semaglutide. Start by letting your healthcare provider know you’d like to change to a different form of your GLP-1 receptor agonist medication. They can recommend the best way to come off injectable semaglutide, which may include slowly tapering down your dose.