Semaglutide oral vs injection: Is oral as effective?

Are you terrified of needles but still want the benefits that semaglutide offers for weight loss? Or maybe you just prefer to take a pill instead of a shot. Oral semaglutide, the active ingredient in brand-name Rybelsus, may be your answer. But is semaglutide oral vs injection as effective for weight loss? Let’s find out.

Before we dive in, here’s some background. 

What is semaglutide? 

Semaglutide belongs to a class of medications called GLP-1 agonists that mimic the natural hormone glucagon-like peptide 1 (GLP-1). Semaglutide specifically acts on the GLP-1 receptors in the pancreas, leading to increased insulin production and decreased glucagon secretion. This helps regulate blood sugar levels in individuals with type 2 diabetes and leads to weight loss as well.

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Semaglutide is the active ingredient in Ozempic, which was first U.S. Food and Drug Administration (FDA) approved to reduce A1C levels in individuals with type 2 diabetes. People taking it also lost weight.

The FDA has since approved an “oral semaglutide” for type 2 diabetes treatment and sold under the brand name Rybelsus with the active ingredient semaglutide. 

The FDA also approved Wegovy for weight loss in people who are obese (have a body mass index [BMI] of 30 or greater) or overweight (have a BMI of 27 or greater) and have at least one weight-related health condition. Wegovy is an injectable medication with the active ingredient of semaglutide.

Some providers prescribe Ozempic or Rybelsus off-label (something not approved by the FDA) for weight loss and to reduce the risk of weight-related health complications. 

How do the oral vs injection forms of semaglutide compare?

When considering semaglutide oral or injection (aka Wegovy or Rybelsus), the choice depends on your specific medical circumstances, your healthcare provider, and individual preferences.

Your options include Ozempic or Wegovy injections or oral Rybelsus, provided your provider prescribes them. In some cases, your provider may recommend a compounded version of semaglutide too.

In addition to improving glycemic control, both injectable and oral semaglutide help with weight management, which is a common challenge for individuals with type 2 diabetes. Weight loss is attributed to the drug’s ability to reduce appetite, which encourages individuals to reduce their caloric intake and lose weight.

Studies suggest that semaglutide, in either form, may reduce atherosclerotic cardiovascular risk, mainly reducing the risk of heart attack, stroke, and cardiovascular death in people with type 2 diabetes.

Similarities between oral vs injectable semaglutide

Because Rybelsus and Wegovy or Ozempic, the oral and injectable forms of semaglutide, use the same active ingredient, they have similar indications of use as well as common side effects. Both forms must be taken consistently to achieve desired results, which requires long-term treatment plans. 

Clinical studies have shown that both injectable and oral formulations of semaglutide (Ozempic and Rybelsus) are effective in lowering A1C levels, an indicator of long-term blood sugar control (glycemic control). Semaglutide users typically see a reduction in this marker, which indicates better management of diabetes. 

As of late 2023, according to reported FDA drug shortages, both forms may be in short supply due to their popularity in helping people lose weight.

Differences between oral and injectable semaglutide

The most notable differences between oral and injectable formulations of semaglutide are the approved uses, route of administration, and dosing. While both formulations have been shown effective at reducing weight, injectable forms come in stronger formulations. 

Wegovy is FDA-approved for weight management in select individuals. Ozempic and Rybelsus are approved to treat type 2 diabetes. Providers can prescribe them for off-label use. Learn more about Ozempic vs Wegovy.

Oral semaglutide (Rybelsus) is taken as a pill, while Ozempic and Wegovy are administered as an injection under the skin. Rybelsus is taken at the same time every day, while injectable semaglutide is taken once a week. There is no oral form of Wegovy.

Rybelsus needs to be absorbed through the digestive system, which may be affected by factors, such as food intake or gastrointestinal issues. It’s best taken on an empty stomach and at least 30 minutes before or after a meal. Injectable semaglutide, on the other hand, bypasses the digestive tract and can be taken with or without food.

Ozempic and Wegovy are typically started at 0.25 mg once weekly for the first month, then increased gradually from there to a maintenance dose of up to 2 mg for Ozempic and 2.4 mg for Wegovy.

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Is oral semaglutide as effective as the injection? 

Both Rybelsus and Ozempic are proven effective at treating type 2 diabetes. Both are also shown to have an added benefit of promoting weight loss. 

A study titled “Once-Daily Oral Semaglutide Versus Injectable GLP-1 RAs in People with Type 2 Diabetes Inadequately Controlled on Basal Insulin: Systematic Review and Network Meta-analysis” and published in Diabetes Therapy looked at how well the oral form of semaglutide works compared to the injectable form for people with type 2 diabetes. The study concluded that oral semaglutide at 14 milligrams lowered blood sugar and weight as effectively, if not more so, than the injectable form. 

Rybelsus and Ozempic may be used interchangeably at specific doses. According to the FDA’s highlights of prescribing information for Rybelsus, people on 14 milligrams of Rybelsus can switch to .5 milligrams of Ozempic after their last dose of Rybelsus. And patients on .5 milligrams of Ozempic can switch to 7 or 14 milligrams of Rybelsus after stopping Ozempic. 

Note that Ozempic may be more effective for people with gastrointestinal problems. Because gastrointestinal conditions can interfere with the effectiveness of Rybelsus.

While Wegovy is approved for weight loss and management, it’s not interchangeable with Ozempic or Rybelsus. 

Advantages and side effects of semaglutide for weight loss

Semaglutide oral and injections lead to weight loss. But, as with any medication, they have side effects.

Advantages

Clinical insight on semaglutide has shown that it can lead to significant weight loss in individuals with obesity. It was found that 86.4% of those who took semaglutide lost 5% of their weight, or more, compared to just 31.5% who took a placebo (sugar pill). For a 300-pound individual, 5% is 15 pounds.

It was also found that semaglutide improves cardiovascular risk factors, such as blood pressure and cholesterol levels, reductions in which have long-term health benefits.

Side effects

An article on the safety of semaglutide states that it does have side effects. Commonly reported issues include gastrointestinal symptoms, such as nausea, vomiting, diarrhea, and constipation. Common side effects are most noticeable when beginning treatment and usually diminish over time.

Although rare, acute pancreatitis has been reported in individuals taking semaglutide. It’s important to be aware of the symptoms of pancreatitis, such as severe abdominal pain, persistent nausea, and vomiting, as these may indicate pancreatitis and require immediate medical attention.

Studies in rodents show an increased risk of getting a thyroid tumor with semaglutide. The relevance of these findings to humans is still under investigation.

Pros and cons of semaglutide: injection vs oral

One of the main advantages of the oral form of semaglutide (Rybelsus) is that it’s less invasive to take. You simply swallow a pill, and you don’t have to worry about poking yourself with a needle. This is more convenient and less intimidating for people who aren’t comfortable giving themselves a shot.

Oral semaglutide must be absorbed through the intestinal tract. Because of this, those with gastrointestinal issues may have better results on the injectable formula. 

Additionally, the oral formulations must be taken at strict dosing schedules which is the same time every day and on an empty stomach. This may be hard for some people to manage.

A key benefit of the injectable form is that it only needs to be taken once a week, making it more convenient for some people. Additionally, because Ozempic is available in stronger doses, it may be more effective for weight loss for people with type 2 diabetes looking to both control blood sugar and lose weight. 

Which is more cost-effective: oral or injection

The list prices for Ozempic and Rybelsus are the same. Novo Nordisk gives a monthly list price of $935.77 for Ozempic and a $935.77 list price for Rybelsus. If you have insurance and your provider covers the medication, you’ll pay less.  Keep in mind though, that off-label use of these medications may not be covered by insurance at all. It’s important to talk with your doctor to find the right formulation for you. 

If your provider suggests Wegovy, it has a list price of $1,349.02 per package, which is a 1-month supply. 

Novo Nordisk offers savings programs for all 3 medications for qualifying individuals. There are also other ways to save on Wegovy and pay less for Ozempic.

Are there alternatives to semaglutide? 

There are alternative medications to semaglutide for type 2 diabetes and alternatives to Wegovy for weight loss. There are other GLP-1 agonists and unrelated medications. Here, we cover a few of the weight-loss-specific medications.

Liraglutide

One prescription alternative to semaglutide is liraglutide. It’s another weekly GLP-1 receptor agonist injection, marketed for weight loss as Saxenda. It’s FDA approved for weight loss in adults and teens 12 to 17 with a BMI of 30 or higher and people with a BMI of 27 or greater with at least one weight-related health condition. 

Liraglutide works by increasing insulin secretion, decreasing glucagon secretion, and slowing gastric emptying, which contributes to better blood glucose control and potential weight loss.

While both liraglutide and semaglutide have proven benefits, they differ in their side effect profiles and patient tolerability. Your healthcare provider may prefer one over the other based on your needs and responses to treatment.

Tirzepatide

Zepbound is the brand name for a drug that contains the active ingredient tirzepatide. It’s approved by the FDA for chronic weight management. A brand specific for the treatment of type 2 diabetes called Mounjaro is the same medication as Zepbound.

Tirzepatide activates GLP-1 receptors and glucose-dependent insulinotropic polypeptide, which helps reduce appetite and food intake and contribute to weight loss. 

More alternatives

Other semaglutide alternatives specifically for weight loss include Contrave (bupropion-naltrexone), Xenical and Alli (orlistat), and Qsymia (phentermine-topiramate).

Research also suggests that some foods boost levels of the Ozempic-like hormone.

The best place to start to determine the right medication and approach for your weight loss or diabetes treatment is with a qualified healthcare provider. You can do that on Klarity Health.

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