Oral vs. Injectable Semaglutide: What’s the Difference?

Many diabetics will be intimately familiar with insulin and the various varieties and analogs that are available to choose from. Perhaps fewer may be aware of adjunct medications that may be prescribed as secondary interventions to complement a holistic diabetes treatment regime. Semaglutide is an example of such a medication and maybe a beneficial addition to your type 2 diabetes treatment that you may wish to discuss with your doctor. You may also be interested in semaglutide for its ability to help promote weight loss in individuals who chronically struggle with weight management.

However, individuals who decide to take semaglutide will have some decisions to make regarding their treatment. Namely, they will need to decide whether to opt for the injectable or orally-administered format of this medication. In this article, we explain a little more about what semaglutide is, who it may be helpful for, and what the different formulations may have to offer. Please note that you should not make any medical decisions based on the information in this article, and you should always discuss with your physician before making any changes to your diabetes or weight loss treatment plans.

What is semaglutide?

Semaglutide is the generic name for a medication used in the treatment of various diseases, including primarily type 2 diabetes, as well as being used off-label as a treatment for obesity and a weight-loss aid.
This drug is meant to mimic the action of a hormone that is naturally produced in our bodies, called GLP-1. Semaglutide is therefore known as a GLP-1 receptor agonist, because it activates the same receptors as GLP-1, albeit in a more effective and sustained manner.

Currently, semaglutide is available in both a daily ingestible format, as well as via weekly subcutaneous injections. These formulations are prescribed under the brand names Rybelsus and Ozempic/Wegovy, respectively.

What is semaglutide used for?

In the decades since insulin was first discovered as an effective treatment for diabetes, pharmaceutical companies have spent billions of dollars in researching and developing novel, modern pharmaceuticals for the treatment of diabetes. Many of these treatments are functional substitutes for insulin, providing the same underlying mechanism of action, but offering improvements in tolerability, convenience, and reductions in adverse side effects.

Still, insulin and its various analogs are not effective for everyone. Some people respond inadequately to insulin treatment alone, and this fact has led to the development of novel categories of diabetes medications that have entirely different mechanisms of action but serve the same goal. Semaglutide is an example of such a medication. It is often used in conjunction with exercise, diet control, and insulin intake, as part of a holistic type 2 diabetes treatment regimen.

Due to certain semaglutide properties, it also has secondary effects that serve other medicinal purposes. Specifically, it has been found to offer benefits for individuals looking to lose body fat. This has led to semaglutide being prescribed off-label for the treatment of obesity in patients who may not suffer from diabetes at all.

How is semaglutide effective in treating diabetes?

Unlike insulin, semaglutide does not directly impact the import of glucose from the bloodstream into cells as a means of regulating blood glucose levels. Rather, it works indirectly to regulate the excretion of insulin from the pancreas in response to the presence of glucose, in order to increase the concentration of insulin in the bloodstream and thereby reduce blood glucose levels.

Semaglutide also slows the progress of food through the gastrointestinal tract, causing carbohydrates and sugars in food to be released in a slower, more controlled manner. This can help smooth out spikes in blood sugar that might otherwise be hard to control following large meals.

It should be noted that the applicability of semaglutide as a diabetes treatment is more limited than that of insulin or insulin analogs. Semaglutide is not used in the treatment of type 1 diabetes or as a treatment for diabetic ketoacidosis. It is solely indicated for the treatment of type 2 diabetes.

How is it effective in treating obesity?

One of the same mechanisms that allow semaglutide to treat diabetes also makes it effective in aiding people with weight loss. As previously stated, semaglutide mimics the function of a hormone called GLP-1. GLP-1 is produced naturally in our intestinal tract when we consume food. One of its roles is to indicate to the rest of our body that we are full by providing a sense of satiety and reducing our urge to eat more food. Unfortunately, this natural hormone does not last very long, and will typically dissipate soon after we have finished our meal, leaving us with a desire to

What are the differences between oral and injectable semaglutide?

Individuals who are prescribed semaglutide for diabetes or weight loss have a couple of options regarding the format of semaglutide they wish to take. Specifically, they can choose between ingesting a semaglutide orally or injecting a semaglutide solution subcutaneously, using a syringe. Each of these formulations offer minor advantages over the other, but both are effective means of taking semaglutide.

Injectable semaglutide has been around for much longer than oral semaglutide. In fact, most of the medications in the GLP-1 receptor agonist family are also injectables, with oral semaglutide being the first to offer an ingestible alternative for type 2 diabetes patients. Before oral semaglutide, there was a technical barrier that prevented these medications from being taken orally, Namely, the digestive system was too harsh on the medications, because the high acidity and presence of digestive enzymes would break down the medication before it could be absorbed through the intestinal lining. Recent innovations in pharmaceutical technology have led to the development of SNAC, which is a material that prevents much of that degradation from occurring. Oral semaglutide tablets are coated in SNAC, thereby enabling them to be administered orally.

Patients who take injectable semaglutide are required to inject the medication once weekly. The injectable dosage is typically 1 mg per injection. Patients who consume semaglutide orally are required to do so daily and at a much higher dosage. The reason for the higher dosage has to do with how the medication is absorbed into the body through the two different routes. It seems that, even with SNAC technology, the gastrointestinal tract is a much less efficient way to get semaglutide into the bloodstream as compared to injecting it directly. To be clear, this does not mean that oral semaglutide is less effective than injectable semaglutide; it simply means that a higher dosage is required to achieve similar efficacy.

Studies have been conducted to compare the efficacy and potential for adverse side effects between oral and injectable semaglutide. While some studies indicate slight differences in favor of one or the other, they generally found that the two formulations are very similar in both their effects and their likelihood of causing side effects like nausea. The choice between the two formulations may therefore simply come down to an individual’s preference between the convenience of taking their medication only once per week, versus their aversion to needles. Otherwise, in the most relevant ways, the two formulations are almost identical in their offerings.

The following chart summarizes the similarities and differences between oral and injectable semaglutide.

In summary, oral and injectable semaglutide are very similar in function. They both carry similar risks of side effects and similar levels of efficacy for type 2 diabetics and those looking for weight loss assistance. The decision to take one over the other may simply come down to one’s individual preferences regarding the frequency of administration, and how one feels about needles.