Oral vs. injectable semaglutide: side-by-side comparison

Semaglutide comes in two forms. Semaglutide tablets go by the brand name Rybelsus (and a soon-to-be-approved oral Wegovy). Injectable semaglutide is available as Ozempic and Wegovy. Beyond the brand names, what’s the difference between oral semaglutide vs. injectable?

A lot, actually. From their FDA-approved indications to dosage strengths, there are several differences between oral vs. injectable semaglutide — as well as some similarities. Below, we break it all down and offer tips for choosing between semaglutide pills vs. injections.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. When combined with diet and exercise, the medication works by controlling blood sugar levels, slowing down digestion, and reducing your appetite. 

Semaglutide is currently available under three brand names, each of which the US Food and Drug Administration (FDA) has approved for different conditions:

• Rybelsus, a daily oral tablet, is approved to improve blood sugar control and reduce cardiovascular risk in adults with type 2 diabetes

• Ozempic, a weekly injection, is approved to improve blood sugar control in adults with type 2 diabetes, reduce cardiovascular risk in adults with type 2 diabetes and heart disease, and slow kidney decline in adults with type 2 diabetes and chronic kidney disease

• Wegovy, a weekly injection, is approved to reduce body weight in adults with obesity or overweight, lower cardiovascular risk in adults with heart disease and obesity or overweight, and treat fatty liver disease in adults

Oral vs. injectable semaglutide: how they work and dosages

Oral and injectable semaglutide differ in their dosages and administration. But they work similarly since they have the same active ingredient.

How they work 

Semaglutide medications work by mimicking GLP-1, a hormone naturally produced by your body. It targets GLP-1 receptors throughout your gastrointestinal tract, pancreas, and brain. 

Specifically, semaglutide works by:

• Slowing down digestion, so you feel full sooner

• Regulating the release of insulin and glucagon after you eat to keep your blood sugar levels stable

• Sending signals to your brain telling it that you’re full

Together, these effects help stabilize blood sugar levels and reduce appetite, making semaglutide an effective treatment for type 2 diabetes, obesity, and more. 

When comparing oral semaglutide vs. injectable, it’s worth noting their difference in bioavailability — that is, how much of the drug enters your bloodstream. Semaglutide tablets have a much lower bioavailability than injections. This is one reason they need to be taken daily instead of weekly like injections.

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Dosages

Oral semaglutide (Rybelsus) comes in two dosage formulations:

• Formulation R1:  3 mg, 7 mg, 14 mg 

• Formulation R2: 1.5 mg, 4 mg, 9 mg

With either formulation, your healthcare provider may have you start at the lowest dosage strength. They will then slowly increase the dose (i.e. titrate up) every 30 days or so until you find a dosage that adequately controls your blood sugar levels. 

For example, a typical dosage titration schedule for oral semaglutide (Rybelsus) might look like this:

Oral semaglutide for weight loss (Wegovy pill) will have a standard daily dose of 25 mg, according to Novo Nordisk, the manufacturer of oral and injectable semaglutide drugs. 

Injectable semaglutide (Wegovy, Ozempic) has its own dosage strengths for each brand-name version:  

• Ozempic: 0.25 mg, 0.5 mg, 1 mg, 2 mg 

• Wegovy: 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg

As with oral semaglutide, healthcare providers typically prescribe a low starting dosage. They then increase it every four weeks or so until you find a dosage that works for you. 

For example, a typical dosage titration schedule for injectable semaglutide might look like this:

Administration

Oral semaglutide is taken once daily in the morning on an empty stomach. This is true for Rybelsus and the Wegovy pill. 

Specifically, you should:

• Avoid food, water, beverages, or medications for at least 30 minutes after taking oral semaglutide

• Swallow oral semaglutide whole with a small amount of water (up to 4 ounces)

Injectable semaglutide is administered weekly via subcutaneous injection. That means you inject it under the skin into the fatty area on your abdomen, thigh, or upper arm. 

Here’s what else you need to know:

• You inject semaglutide every week, on the same day each week, at any time during that day (with or without food). 

• You should rotate injection sites weekly so that you’re not doing the injection in the exact same place every time.

• If needed, you can change your semaglutide injection day, as long as it’s been at least two days since your last dose. It’s a good idea to check with your healthcare provider before changing your dosing day so they can help you make the change safely.

Semaglutide tablets and injections share many similar side effects, since they both contain semaglutide as the active ingredient. 

The most common side effects of both oral and injectable semaglutide include

• Nausea

• Abdominal pain

• Diarrhea

• Vomiting

• Constipation 

Injectable semaglutide (Ozempic, Wegovy) may also cause reactions at the injection site, such as rash or irritation. But these are rare. 

Both oral and injectable semaglutide carry similar risks, including:

• Acute pancreatitis

• Diabetic retinopathy complications (diabetes-related vision changes)

• Hypoglycemia (low blood sugar), especially when used with insulin

• Kidney or gallbladder issues

• Severe gastrointestinal reactions

• Allergic reactions

• Pulmonary aspiration during general anesthesia or deep sedation

Additionally, Wegovy carries warnings for increased heart rate and suicidal behavior or ideation.

All forms of semaglutide carry a black box warning for thyroid tumors based on animal studies. While it’s unknown if semaglutide has the same effect in humans, people with a personal or family history of thyroid cancer should not take oral or injectable semaglutide.

Injectable semaglutide, particularly Wegovy, may be more effective for weight loss than oral semaglutide, according to clinical trials. 

• In 68 weeks (about a year and a half), people taking Wegovy lost nearly 15% of their body weight (~34 pounds). 

• In roughly the same time frame, people taking oral semaglutide (Rybelsus) lost about 4.2% of their body weight (7.5 pounds).

• In 64 weeks (about a year and three months), people taking oral semaglutide (Wegovy pill) lost 13.6% of their body weight (~31 pounds). 

Injectable semaglutide may be slightly more effective for blood sugar control than oral semaglutide, according to clinical trials.

• Oral semaglutide (Rybelsus) reduces HbA1c levels by 1.2%–1.4% at week 26, depending on the dosage strength you’re taking. 

• Injectable semaglutide (Ozempic) reduces HbA1c levels by 1.4%–1.6% at week 30, again depending on the dosage strength. 

So, in nearly the same amount of time, injectable semaglutide reduced blood sugar levels to a larger extent. 

However, other studies have found that the difference in blood sugar control between oral vs. injectable semaglutide is not statistically significant.

Yes. In fact, the FDA is expected to approve an oral semaglutide specifically for weight loss (Wegovy pill) by the end of 2025. 

In May 2025, Novo Nordisk, the maker of Rybelsus, Wegovy, and Ozempic, applied for FDA approval of an oral version of Wegovy. The manufacturer did this after completing a 64-week OASIS 4 phase 3 trial. It found that 25 mg of oral Wegovy daily 25 mg of oral Wegovy reduced body weight by 13.6% in 64 weeks (about a year and three months).

“Most of my diabetics prefer Ozempic injection to the Rybelsus pill, both of which are semaglutide variants,” says Jennifer Brown, MD, ABOM, ABFM, a dual board-certified physician in family medicine and obesity medicine. “It will be interesting to see if real-world patients prefer Wegovy injections over oral Wegovy.”

Choosing the best form of semaglutide for you — semaglutide pills vs. injection — depends on your medical situation, lifestyle, and personal preferences. Here are some of the key decision factors to consider:

1. Your weight loss goals. If your main goal is to lose weight, injectable semaglutide, particularly Wegovy, is likely your best bet. Wegovy can drive nearly 15% weight loss over a year and a half. While Ozempic and Rybelsus can drive some weight loss, it’s not as significant as Wegovy.

2. Your comfort with injections. To take Ozempic or Wegovy, you’ll need to inject yourself once a week. Oral semaglutide can be a preferred option for people who have an aversion to injections, Dr. Brown says.

3. Your lifestyle (vs. administration). Frequent flyer? A shelf-stable treatment may be a better fit for you. Oral semaglutide is taken daily and doesn’t need to be refrigerated. But the rigidity of oral semaglutide’s morning administration can be a downside for some people, Dr. Brown says. Sound like you? In that case, injectable semaglutide may be more up your alley, as it’s taken weekly. Just remember: It needs to be kept at certain temperatures. 

4. Other medical conditions. Health insurance plans typically only cover a medication when it’s prescribed for an FDA-approved condition. In other words, it might be tougher to get Ozempic covered for weight loss than Wegovy. However, both forms of injectable semaglutide are approved to treat a number of conditions. Your healthcare provider can help you determine your best bet at securing coverage.

5. Your insurance coverage and budget. Oral and injectable semaglutide drugs have relatively high list prices: $997.58 for Rybelsus, $997.58 for Ozempic, and $1,349.02 for Wegovy. Novo Nordisk offers savings programs for certain brand-name drugs, but they come with eligibility requirements. You can also get injectable semaglutide for a reduced price if you pay with cash. Through Ro, for example, Wegovy pens cost $199-$349 per month when you opt for self-pay. 

Your healthcare provider can help you determine whether oral or injectable semaglutide may be a better fit for you, based on your personal health situation and goals. 

Oral semaglutide may be better if:

• You have needle phobia or don’t like injections

• You don’t want to worry about storing or properly disposing of needles and pens

• You like the routine of taking a daily pill

• Your main goal is to treat type 2 diabetes, with less of a need for weight loss

• Your health insurance offers better coverage for Rybelsus vs. Ozempic or Wegovy

Injectable semaglutide may be better if:

• You prefer the flexibility of only having to do an injection once a week, at any time of day

• You don’t want to wait 30 minutes every morning before eating, drinking, or taking other medication after your oral semaglutide dose

• You’re not taking other medications that have to be taken in the morning

• You want greater blood sugar control or weight loss results

• You also have fatty liver disease, chronic kidney disease, or heart disease

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By now, you should be well-versed in oral semaglutide vs. injectable semaglutide. But after reading so much information, it can be hard to remember the high-level highlights. Hey, we get it. So, here are the main differences and similarities between oral and injectable semaglutide to help keep them top-of-mind:

• They work the same. Oral semaglutide and injections both work by mimicking the GLP-1 hormone to help control blood sugar, slow digestion, and reduce appetite. 

• Dosage strengths differ. Each form of semaglutide comes in different dosage strengths, but they’re all titrated up gradually until you find an effective dosage. 

• Dosing frequency and administration differ. Oral semaglutide is taken daily in the morning on an empty stomach (at least 30 minutes before food, water, and other medications), while injections are done weekly at any time of day.

• Side effects are similar. Gastrointestinal side effects are common with both oral and injectable semaglutide. Semaglutide injections may also cause injection site reactions, and Wegovy has a longer list of side effects in general.

• Semaglutide injections may produce more weight loss. Injectable semaglutide (especially Wegovy) may be more effective at weight loss and slightly more effective at blood sugar control.