Oral Semaglutide Vs. Injection Semaglutide

Semaglutide is a medication that has gained popularity for its effectiveness in weight management and tackling obesity. It is available in two forms: oral tablets and injections. Both forms have been found to be effective in facilitating weight loss and have their own set of pros and cons. In this article, we will explore the differences between oral tablets and injections of semaglutide, their dosage timing, injection sites, and their effectiveness for people without diabetes.

Oral vs. injectable semaglutide

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 receptor agonist) that can help treat type 2 diabetes by increasing insulin production and reducing blood sugar levels. It also sends signals to the brain that you are not hungry, making it effective for weight loss.

The Food and Drug Administration (FDA) has approved different forms of semaglutide for treating type 2 diabetes mellitus and weight loss. It is important to note that semaglutide is not approved for use with type 1 diabetes or diabetic ketoacidosis.

Semaglutide is commonly sold under the brand names Ozempic, Wegovy and Rybelsus all of which are manufactured by Novo Nordisk. Semaglutide is the only GLP-1 receptor agonist that is available in both an injectable and oral formulation. Wegovy and Ozempic are subcutaneous injection versions, while Rybelsus is an oral tablet.

Effectiveness of oral semaglutide vs. injection semaglutide

The efficacy of once-weekly subcutaneous semaglutide and once-daily oral semaglutide has been investigated in the global SUSTAIN and PIONEER phase III clinical trial programs in a range of clinical settings.

Patients with early type 2 diabetes managed with diet and exercise only

In clinical trials involving patients with early type 2 diabetes who were managed with diet and exercise alone, both oral semaglutide and injection semaglutide demonstrated significant reductions in glycated hemoglobin (HbA1c) levels from baseline. Subcutaneous semaglutide 1.0 mg dose and oral semaglutide 14 mg dose monotherapy resulted in HbA1c reductions of 1.6% (at 30 weeks) and 1.4% (at 26 weeks), respectively, compared to the placebo group.

Patients with established type 2 diabetes treated with one to three oral antidiabetic drugs (OADs)

Studies involving patients with established type 2 diabetes who were already receiving one to three OADs showed that both oral and injection semaglutide were effective in reducing HbA1c levels. Subcutaneous semaglutide (0.5 mg and 1.0 mg) and oral semaglutide (7 mg and 14 mg) demonstrated superior HbA1c reductions compared to sitagliptin, exenatide extended release, dulaglutide, canagliflozin, or insulin glargine.

Patients with advanced, uncontrolled type 2 diabetes on insulin

For patients with advanced, uncontrolled type 2 diabetes who were already on insulin therapy, both oral and injection semaglutide showed significant reductions in HbA1c levels. Subcutaneous semaglutide (0.5 mg and 1.0 mg) and oral semaglutide (7 mg and 14 mg) were more effective than placebo in reducing HbA1c levels.

Body weight reductions with oral semaglutide vs. injection semaglutide

Both oral and injection semaglutide demonstrated significant reductions in body weight in various patient populations.

Patients with type 2 diabetes managed with diet and exercise only

In patients with early type 2 diabetes, oral semaglutide and injection semaglutide monotherapy led to greater reductions in body weight compared to placebo. Subcutaneous semaglutide 1.0 mg and oral semaglutide 14 mg resulted in weight reductions of 4.5 kg and 3.7 kg, respectively, while placebo only resulted in weight reductions of 1.0 kg and 1.4 kg, respectively.

Patients with established type 2 diabetes treated with one to three OADs

In patients with established type 2 diabetes already receiving one or two OADs, both oral and injection semaglutide demonstrated significant weight reductions compared to the respective comparators. Subcutaneous semaglutide 1.0 mg reduced body weight significantly more than once-weekly exenatide extended release, dulaglutide, or liraglutide. Oral semaglutide 14 mg showed similar weight reductions to once-daily liraglutide 1.8 mg when added to metformin ± an SGLT2 (sodium-glucose co-transporter-2) inhibitor.

Patients with advanced type 2 diabetes on insulin

Both oral and injection semaglutide were effective in reducing body weight in patients with advanced, uncontrolled type 2 diabetes already on insulin therapy. Subcutaneous semaglutide (0.5 mg and 1.0 mg) and oral semaglutide (7 mg and 14 mg) led to significant weight reductions compared to placebo.

Dosage timing

The dosage timing for semaglutide differs between oral tablets and injections. Subcutaneous semaglutide is typically administered as weekly injections on the same day. The dosage may be increased after 4 weeks if necessary. It is important not to stop taking semaglutide without consulting your doctor. If a dose is missed, it should be taken as soon as remembered, with certain guidelines depending on the specific medication.

Once daily oral semaglutide tablets are taken once a day, preferably in the morning, at least 30 minutes before eating or consuming other medications. It is recommended to take the tablet with a small amount of water and to wait at least 30 minutes before eating. If other medications need to be taken in the morning on an empty stomach, it is important to discuss this with your doctor.

Pros and cons

Both oral tablets and injectable semaglutide have their own set of pros and cons. Oral tablets do not require the use of needles, making them more convenient for individuals who may have a fear of needles or dislike injections. They are taken once a day and have been found to be effective for weight loss. However, oral tablets may cause gastrointestinal side effects such as nausea, vomiting, and abdominal pain. They also need to be taken on an empty stomach in the morning, which may require some adjustment to one’s daily routine. While tolerability may vary, these side effects should pass.

On the other hand, injectable semaglutide requires the use of needles and is typically administered once a week. It does not matter whether food or liquid has been consumed before or after the injection. Injectable semaglutide has been found to be effective for weight loss, but it can also cause injection site reactions. It is important to rotate the injection site after each shot to prevent the development of scar tissue.

Injection sites

Semaglutide injections can be administered in the upper arm, thigh, or stomach. It is recommended to inject semaglutide in the same area as insulin injections, but not directly next to each other. It is also important to rotate the injection site after each shot to ensure proper absorption of the medication and to prevent the development of scar tissue.

Semaglutide for people without diabetes

While semaglutide injection Wegovy is FDA approved for weight loss in people with and without diabetes, Ozempic and Rybelsus are not specifically cleared for weight loss use. These drugs are licensed as a diabetes treatment to lower blood glucose levels in type 2 diabetics. However, doctors in clinical practice may choose to prescribe Ozempic and Rybelsus off-label for weight loss alone. Research has shown the weight loss benefits of semaglutide injections in individuals without diabetes. It is important to keep in mind that both oral and injectable forms of semaglutide can cause adverse events, regardless of whether a person has diabetes or not.

Takeaway

Semaglutide is a medication that has been approved for weight loss and treating type 2 diabetes. It is available in oral tablets and injectable forms. Research suggests that oral semaglutide is as effective as injectable semaglutide for weight loss and reducing A1C levels. Both forms of semaglutide have their own pros and cons, and it is important to work closely with your healthcare team to determine the best form for your lifestyle and health needs.

Taking semaglutide requires adherence to the recommended dosage timing and injection techniques. It is also important to be aware of the possible side effects and to contact your doctor if you have any concerns. Semaglutide can be an effective tool for weight loss, but it should be used in conjunction with a healthy diet and lifestyle changes for long-term success.

Additional Information:

• It is important to consult with a healthcare professional before starting any medication, including semaglutide
• Semaglutide should not be used by pregnant or breastfeeding individuals without medical advice
• The effectiveness of semaglutide may vary between individuals, and it may not be suitable for everyone. It is important to discuss potential risks and benefits with your doctor

Sources

• What to Know About Semaglutide: Oral Tablets vs. Injections
• Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation – PMC