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Comparing Oral vs. Injectable Semaglutide

Craig Primack MD

Reviewed by Craig Primack, MD, FACP, FAAP, FOMA

Written by Jill Seladi-Schulman, PhD

Updated 10/11/2024

It’s hard to watch the news or scroll through social media without encountering stories about weight loss drugs like semaglutide (the active ingredient in Ozempic® and Wegovy®). 

Media coverage of semaglutide often focuses on its injectable forms, but did you know there’s also a brand of semaglutide that can be taken orally? It’s called Rybelsus®.

How does oral semaglutide work compared to the injectable version? You may be curious if one form of semaglutide is more effective than the other or if one type causes more side effects. In any case, it’s worth exploring oral semaglutide versus injectable.

Keep reading as we compare oral semaglutide versus injectable semaglutide.

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It works by mimicking GLP-1 hormone, which is naturally produced in your intestines. 

Semaglutide has several effects on the body, including:

  • Increasing how much insulin the pancreas makes and releases into the bloodstream helps lower blood sugar (glucose) when it is high

  • Blocking the body from making glucagon, a hormone that increases blood sugar

  • Slowing the emptying of the stomach, helping you feel full quicker and longer

  • Interacting with parts of the brain to reduce appetite and signal to the body that you’re full

Semaglutide was originally developed to lower blood glucose in people living with type 2 diabetes. However, its popularity for weight loss has skyrocketed in recent years.

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The U.S. Food and Drug Administration (FDA) has — so far — approved three products containing semaglutide. All three of these prescription drugs are made by the company Novo Nordisk, and although the active ingredients are the same, each has a different brand name.

Rybelsus is an oral medication, while Ozempic and Wegovy are injected.

Here’s what to know about Rybelsus semaglutide tablets versus injections for weight loss and diabetes.

Rybelsus

Rybelsus tablets are FDA-approved to treat type 2 diabetes. They’re meant to be used along with a nutritional plan and regular physical activity to manage blood sugar levels.

This medication doesn’t have FDA approval for weight loss, but some healthcare providers prescribe Rybelsus off-label for this purpose. (Off-label use is when a drug 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.

As you’re probably aware, Ozempic is well-known for its weight loss effects. Healthcare providers can prescribe it off-label for this purpose at their own discretion.

Wegovy

Wegovy is FDA-approved to be used alongside healthy eating and exercise to treat obesity.

This medication may also be prescribed to people with overweight who have a weight-related condition like type 2 diabetes, high blood pressure (hypertension), or dyslipidemia (high cholesterol or fats in the blood).

Wegovy is the only semaglutide product approved specifically for weight management. But as noted, the other two semaglutide drugs from Novo Nordisk (Ozempic and Rybelsus) may be prescribed off-label for weight loss.

See our guide to Wegovy vs. Ozempic for a deeper dive comparing the two.

Compounded Semaglutide

There’s also compounded semaglutide injections. Compounded medications, like those available on the Hers platform, are not FDA-approved. However, they contain the same active ingredient as the brand-name drugs Ozempic and Wegovy. 

Compounded semaglutide is a more affordable option, with monthly plans starting at $199 for those who qualify. 

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 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, while Rybelsus led to an average weight loss of over eight pounds.

It’s important to note, however, 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.

Comparing clinical trials is one thing, but you may be wondering about people’s real-world experiences with oral semaglutide versus injectable semaglutide. 

According to Dr. Craig Primack, a physician specializing in obesity medicine, “In my experience, 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."

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

Novo Nordisk, the company that makes Rybelsus, Ozempic, and Wegovy, 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 medication lost only 1.8 percent of their baseline body weight.

This weight loss is actually slightly more than what was seen in clinical trials of Wegovy. In those studies, participants taking Wegovy lost an average of 14.9 percent of their body weight after 68 weeks.

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

  • Nausea

  • Vomiting

  • Diarrhea

  • Constipation

  • Abdominal pain

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

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

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

Oral semaglutide 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, 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 our skin.

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.

Learn more about how to inject semaglutide.

There are a few injection sites you can use to inject subcutaneous semaglutide. These include the abdomen, thighs, and upper arms.

It’s perfectly normal to have concerns about pain during or after an injection. If this is 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.

  • Your injection can be done with or without food.

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In terms of which form of semaglutide is best, there’s no one-size-fits-all answer. The version a medical provider recommends can depend on what it’s being used for.

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 the only form of semaglutide currently FDA-approved for weight management.

  • Patient preference can also play a role. 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 the goal is weight loss and you’re interested in Rybelsus for weight loss, a healthcare provider might prescribe it off-label.

Those curious about semaglutide for type 2 diabetes or weight loss should consult a healthcare professional. Your provider can make medication and lifestyle recommendations that fit your individual needs.

If you’re interested in compounded semaglutide, you can start with our quick virtual weight loss assessment.

And for those who prefer swallowing tablets rather than injecting medication, we also have custom oral medication kits for weight loss starting at just $79 per month.

13 Sources

  1. Chowdhury SR, et al. (2024). Real-world use of oral and subcutaneous semaglutide in routine clinical practice in the UK: A single-centre, retrospective observational study. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10951141/
  2. Collins L, et al. (2024). Glucagon-like peptide-1 receptor agonists. https://www.ncbi.nlm.nih.gov/books/NBK551568/
  3. Davies M, et al. (2017). Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5817971/
  4. Fadini GP, et al. (2024). Oral or injectable semaglutide for the management of type 2 diabetes in routine care: A multicentre observational study comparing matched cohorts. https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.15554
  5. Meier JJ. (2021). Efficacy of semaglutide in a subcutaneous and an oral formulation. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269445/
  6. National Library of Medicine. (2024). Semaglutide injection. https://medlineplus.gov/druginfo/meds/a618008.html
  7. Novo Nordisk. (2023). Company announcement: Novo Nordisk A/S: Oral semaglutide 50 mg achieved 15.1% weight loss (17.4% if all people adhered to treatment) in adults with obesity or overweight in the OASIS 1 trial. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=166110
  8. Ozempic (semaglutide) injection, for subcutaneous use. (2022). https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/209637Orig1s009lbl.pdf
  9. Rybelsus (semaglutide) tablets, for oral use. (2024). https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213051s018lbl.pdf
  10. Usach I, et al. (2019). Subcutaneous injection of drugs: Literature review of factors influencing pain sensation at the injection site. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822791/
  11. U.S. Food and Drug Administration (FDA). (2024). Medications containing semaglutide marketed for type 2 diabetes or weight loss. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss
  12. Wegovy (semaglutide) injection, for subcutaneous use. (2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/215256s007lbl.pdf
  13. Wilding JP, et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
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Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references. See a mistake? Let us know at [email protected]!

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