Oral vs Injectable Semaglutide: Ozempic or Rybelsus?

Key Points

• Injectable forms come as Ozempic and Wegovy with weekly dosing, while oral Rybelsus is a pill taken daily every morning
• Ozempic is used to treat diabetes, while Wegovy is used for weight loss and to reduce the risk of heart disease. Oral semaglutide is approved to manage type 2 diabetes
• Your body absorbs nearly 90% of injected semaglutide, while the stomach breaks down some of the oral semaglutide, reducing its effectiveness in the body
• All types of semaglutide need a nutritious diet and regular exercise as part of the treatment plan

Semaglutide has been helping people lose weight and manage their blood glucose. However, not all types of semaglutide are alike. There are injectable and oral versions, and the type of semaglutide you take matters.

Understanding why doctors choose weekly shots for some people and daily pills for others comes down to absorption science, health goals, individual treatment goals, convenience, and how you may feel about needles. Here’s a comparison guide between oral vs. injectable semaglutide.

Types of semaglutide

"Semaglutide works by slowing digestion, reducing appetite, and helping your pancreas release insulin when blood sugar levels are high," explains physician Gia Eapen, MD. "This combination of effects helps control blood sugar and can lead to weight loss.

Injectable semaglutide is sold under the brand names of Ozempic and Wegovy:

• Ozempic is FDA-approved to help adults with type 2 diabetes control their blood sugar when combined with healthy eating and exercise. It has also been shown to protect against heart attacks, strokes, and death in people with diabetes. Recently, it was also approved by the FDA to protect kidney function in people with diabetes and kidney problems
• Wegovy is FDA-approved to help with weight loss in adults who are obese and have a weight-related health condition. Doctors can also prescribe it for kids 12 and older who are obese. It is also approved to prevent serious heart problems in overweight or obese adults with heart disease.

Oral semaglutide is sold under the brand name Rybelsus. Rybelsus is FDA-approved to manage blood sugar in adults with type 2 diabetes when combined with diet and exercise.

"If you’re wondering whether oral or injectable semaglutide is right for you, please consult your healthcare provider who can advise you based on your condition and health goals, and individual circumstances," notes  Eapen, MD.

Oral vs injectable semaglutide: How are they administered?

Injectable semaglutide administration

Taking injectable semaglutide (Ozempic, Wegovy) is straightforward with convenient once-weekly dosing. You simply use the pre-filled pen once per week, injecting subcutaneously into your abdomen, thigh, or upper arm.

Oral semaglutide administration

Rybelsus (oral semaglutide) is taken as a daily pill. It must be taken first thing each morning on an empty stomach with no more than 4 ounces of water. A mandatory 30-minute waiting period follows before consuming any food, beverages, or other medications.

Oral vs injectable semaglutide: Which one is better absorbed in the body?

Your body absorbs injectable and oral semaglutide in different ways.

Injectable semaglutide absorption is more efficient than oral semaglutide. When you inject the medicine under your skin, nearly all of it enters your bloodstream and begins to work. Injectable semaglutide has a high bioavailability of 89%, which means that nearly all of the injected semaglutide reaches the bloodstream efficiently.

In general, stomach acid breaks down most oral medicines before they can get into the blood. To address this issue, Rybelsus contains a helper ingredient called SNAC, which protects the medicine as it travels through the stomach. Even with this special protection, the body only absorbs about 0.4-1% of each Rybelsus pill.

"This difference in absorption explains why taking Rybelsus correctly is so important. If you don't follow the strict timing rules (empty stomach, waiting 30 minutes), even less of the medicine may get absorbed," explains Eapen, MD.

Oral vs injectable semaglutide? Which one is better for weight loss

Currently, injectable semaglutide (Wegovy) is the approved semaglutide drug for weight loss. Oral semaglutide is not FDA-approved for weight loss.

In one study, people using Wegovy lost approximately 15% of their body weight over 68 weeks (approximately 16 months). This means someone weighing 200 pounds might lose 30 pounds. Most people (86%) lost at least 5% of their weight in the clinical study.

Oral vs injectable semaglutide? Which one is better for type 2 diabetes?

Both Ozempic and Rybelsus are effective in controlling blood sugar levels, but some studies suggest that Ozempic (injectable semaglutide) may be more effective.

A1C reduction with Rybelsus (oral semaglutide)

In one clinical study, people taking oral semaglutide daily lowered their A1C (a blood sugar test) by 1.2% over 26 weeks.

A1C reduction with Ozempic (injectable semaglutide)

Research shows people using the 2 mg ozempic dose saw an average A1C drop of 2.2 points after 40 weeks. Those using a 1.0 mg dose experienced a drop of 1.9 points at the same time.

Oral vs injectable semaglutide? Which one is better for heart health?

Heart protection is a big difference between these medicines.

Wegovy is specifically approved to reduce the risk of severe heart problems in adults with heart disease who are overweight. Ozempic can also protect the heart in people with diabetes and known heart disease

Rybelsus (oral semaglutide) doesn't have FDA approval for heart protection.

Oral vs injectable semaglutide dosage

Oral semaglutide dosage

Rybelsus dosing starts low and builds up: 3 mg once daily for the first month, then 7 mg daily for the second month. If you need better blood sugar control, your doctor might increase it to 14 mg daily. You take it every morning at the same time.

Injectable semaglutide dosage

Ozempic dosing begins at 0.25 mg once weekly for the first month to help your body adjust, then increases to 0.5 mg weekly for at least four weeks. Your doctor may increase it to 1 mg or 2 mg weekly, based on how your blood sugar responds and how you feel.

Wegovy dosing starts at 0.25 mg weekly and goes up every four weeks until you reach 2.4 mg weekly.

"For both oral semaglutide and injectable semaglutide, your healthcare provider will start you off with lower doses so that your body adjusts to the medication. This gradual approach helps minimize side effects like nausea and stomach upset while allowing your system to adapt to the treatment. The dose is gradually increased over several weeks until the most effective level for your individual needs is reached," says Eapen, MD.

Oral vs injectable semaglutide? Which one has fewer side effects?

Both injectable semaglutide and oral semaglutide can cause similar side effects. However, some research has shown that discontinuation due to side effects was higher with oral vs. injectable semaglutide.

Stomach issues are the most common side effects of both oral and injectable semaglutide. These include feeling sick to your stomach, throwing up, diarrhea, constipation, and belly pain. These usually occur as your body adjusts to the medication, then improve as your body becomes accustomed to it.

Serious side effects are rare but can happen with both types of semaglutide. These include pancreas inflammation, gallbladder problems, and kidney issues.

"Whether you're using injectable semaglutide or oral semaglutide, if side effects persist or become concerning, please contact your healthcare provider immediately. They can adjust your dose, provide management strategies, or determine if a different treatment approach might be better for you," says Eapen, MD.

Oral vs. injectable Semaglutide: Insurance coverage

Insurance coverage for semaglutide medications may depend on your individual health plan and the reason for taking the drug.

Most insurance companies are more willing to cover medicines that treat diabetes, so Ozempic and Rybelsus often receive better coverage since they're approved for blood sugar control.

Wegovy may face greater coverage challenges because it's primarily used for weight loss, and some insurance plans may not cover weight loss medications.

The bottom line is that coverage rules change frequently and vary widely between insurance companies.  Before starting any of these medications, call your insurance company directly to ask about your specific coverage.

Additionally, ask your doctor's office to check with your insurance provider; they may know which forms are most likely to be covered under your plan.

Semaglutide and diet

Healthy eating and exercise are recommended when taking semaglutide, regardless of whether you’re taking the oral or injectable version.

Rita Faycurry, RD, Registered Dietitian, says, "Semaglutide works by helping control appetite and blood sugar, but pairing it with a balanced diet and regular physical activity is recommended."

Eat a balanced diet with portion control, focusing on a variety of protein sources, vegetables, whole grains, and healthy fats. Avoid greasy, fatty, or spicy foods that might make you feel sick and limit alcohol.

A registered dietitian can help create a personalized semaglutide diet plan that works with your treatment.

Final thoughts: Oral vs. injectable semaglutide

Both oral and injectable semaglutide can work effectively for their approved uses, but your healthcare provider will determine what is best for your specific situation and health goals.

Injectable semaglutide offers the broadest range of benefits, with FDA approval for weight loss, type 2 diabetes management, and heart health protection. Oral semaglutide is currently only approved for type 2 diabetes management.

Work closely with your healthcare provider to select the form that aligns best with your treatment needs.

Frequently asked questions (FAQs)

Is oral semaglutide as effective as injections?

Both oral semaglutide and injectable semaglutide can aid in blood sugar control for the management of type 2 diabetes. However, only injectable semaglutide is FDA-approved for weight loss and for heart health.

What are the disadvantages of oral semaglutide?

Oral semaglutide must be taken daily in the morning on an empty stomach, with a 30-minute wait before eating. One study also found that discontinuation due to side effects was higher among those taking oral semaglutide compared to those taking injectable semaglutide. Oral semaglutide is also only FDA-approved to manage type 2 diabetes, not weight loss.

Is oral semaglutide FDA-approved?

Yes, oral semaglutide is FDA-approved as Rybelsus for treating type 2 diabetes in adults when combined with diet and exercise. However, it is not approved for weight loss or heart protection like injectable semaglutide.

Can you switch from injectable to oral semaglutide?

Talk to your healthcare provider, who can assess whether you can switch from injectable to oral semaglutide. They will evaluate your current dose, health goals, and how well your body responds to the medication, among other factors, before offering their recommendation.

Switching might require careful monitoring and dose adjustment by your healthcare provider. One study found that participant glucose levels increased (around 0.2% A1C change) when people switched from once-weekly 0.5mg injectable semaglutide to once-daily 7mg oral semaglutide.

Get a personalized semaglutide diet plan, covered by insurance.

The views expressed by authors and contributors of such content are not endorsed or approved by Fay and are intended for informational purposes only. The content is reviewed by Fay only to confirm educational value and audience interest. You are encouraged to discuss any questions that you may have about your health with a healthcare provider.