Semaglutide Pills vs. Injection: Which Form Can Give You Better Results?

Published

Nov 20, 2023

Semaglutide Pills vs. Injection: A Detailed Comparison.

Doctor consulting a patient
Doctor consulting a patient
Doctor consulting a patient

Semaglutide is the active ingredient in some of the newer FDA-approved diabetes and weight management medications.¹ Healthcare providers often recommend it for patients who hit a plateau on their weight loss journey despite a healthy diet and regular exercise. 

Initially, Semaglutide was only available in an injectable form.² However, in 2019, the FDA approved an oral version.³ Many people taking or considering Semaglutide for weight loss may be wondering how the pill form compares to the injectable version. 

This article will explain what Semaglutide is and how it works. We’ll also compare the two commercially available forms of Semaglutide — the injection vs. the pill — and explore the benefits of Compounded Semaglutide for patients looking for an effective, affordable weight loss solution.

What Is Semaglutide And What Does It Do?

Semaglutide is a member of the class of medications known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs).⁴ That means it has actions similar to the human hormone GLP-1. The intestines secrete this substance into the blood in response to food intake and absorption.

GLP-1 triggers various processes upon reaching the targeted organs. In the brain, it suppresses the appetite centers, diminishing food cravings. In the pancreas, it stimulates insulin secretion and inhibits glucagon release. In the stomach, it slows down the movement of food, so nutrients aren’t easily absorbed in the intestines.

Together, these mechanisms prevent steep rises in blood sugar levels after a meal. They likewise limit overall caloric intake, which is key to weight reduction. 

GLP-1 only remains in the cells for a few minutes, then it gets broken down and excreted in the kidneys. Therefore, the hormone’s effects are fleeting. Semaglutide’s structure and actions are similar to GLP-1’s, but it’s designed to stay much longer — about a week — in the body. 

Semaglutide is a peptide or protein-like medication. Normally, peptides break down easily in the presence of intestinal enzymes and can be deactivated by liver enzymes. Taking them by mouth can reduce their amounts significantly before reaching their target tissues. That’s why most peptide medications are in injectable forms.⁵

However, scientific innovations have made it possible to develop an oral version of Semaglutide that can reach the target organs more easily, making its administration more convenient for patients. The question now is: How does it compare to the injectable form?

GLP-1’s target organs and actions

Is Oral or Injectable Semaglutide Better?  

Currently, there are no clinical studies directly comparing oral to injectable Semaglutide for weight loss. Much of what we know about their weight-reducing effects comes from clinical trials measuring them against other medications or placebo. 

Is Oral Semaglutide as Effective as Its Injectable Version?

While there are no direct comparisons between oral and injectable Semaglutide, four clinical trial programs have studied or are currently studying how both forms help patients: 

  • SUSTAIN

  • PIONEER

  • STEP

  • OASIS⁶

Noteworthy findings related to weight management from the trials are summarized below.

1. SUSTAIN

“SUSTAIN” stands for “Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes.” One of its findings was that once-weekly low-dose (0.5-1.0 mg) Semaglutide injections led to greater weight loss than placebo, sitagliptin, insulin glargine, and other diabetes medications used in the study. More patients also achieved >5% reduction in body weight, which is the minimum needed for better cardiovascular health.⁷

The SUSTAIN trials paved the way for the FDA approval of Ozempic, the first injectable Semaglutide product.

2. PIONEER

“PIONEER” means “Peptide Innovation for Early Diabetes Treatment.” This clinical trial program showed that 14 mg once-daily oral intake of Semaglutide had weight-reducing effects similar to empagliflozin and superior to older GLP-1 RAs, sitagliptin, and the other antidiabetic medications used in the study.

The PIONEER program’s results are the basis for the approval of Rybelsus, the first oral Semaglutide formulation in the market.

3. STEP

“STEP” is short for “Semaglutide Treatment Effect in People with Obesity.” It studied the effects of high-dose (2.4 mg) injectable Semaglutide in patients with weight management difficulties, with and without diabetes. The STEP research showed that injectable Semaglutide made people lose significantly more weight than placebo. 

The STEP trials led to the approval of Wegovy, a high-dose Semaglutide injectable made specifically for weight loss resistance with or without concomitant diabetes.

4. OASIS

In May 2023, it was reported that 50 mg of oral Semaglutide once daily resulted in 15.1% weight loss in people with weight loss resistance.⁸ It’s superior to placebo and comparable to injectable Semaglutide. 

Therefore, in terms of efficacy, it appears that oral Semaglutide is as effective as its injectable counterpart in chronic weight management when combined with lifestyle changes. Participants in these clinical trial programs paired the treatment with a healthy diet and exercise.

Provider using a green measuring tape

What Are the Recommended Doses and the Advantages of Each Route?

For injectable Semaglutide, dosing for weight loss may start at 0.25 mg once weekly, increasing every 4 weeks until you reach the maintenance dose of 2.4 mg a week.⁹ The main advantage of injectables over oral medications is that they ensure that the levels reaching the target tissues are sufficient. 

Meanwhile, the current recommendations for oral Semaglutide dosing are based on diabetes guidelines.¹⁰ Your provider may set the initial dose to 3 mg once daily, increasing to 7 mg after 30 days, then to 14 mg after another 30 days if blood glucose control is inadequate. Because oral medications go through the digestive system before reaching the target cells, increasingly larger daily doses are required when using oral Semaglutide medications.

The main advantage of oral medications is that they help people avoid pain and injection site reactions.¹¹ Such reactions can hinder treatment compliance.¹²

How Fast Does Each Form of Semaglutide Work?

For patients on injectable Semaglutide, an average of 5.9% weight loss has been observed after 3 months and 10.9% after 6 months.¹³

With proper diet and exercise, studies show that significant weight loss is possible as early as 6 months after starting oral Semaglutide. 

In the first several weeks of treatment, you and your provider will work together to find your optimal dose.

Couple wearing green, meditating

Does Oral or Injectable Semaglutide Wear Off When You Stop?

Based on the STEP 4 study results, patients who stop taking injectable Semaglutide before completing their treatment program may regain the weight they have lost.¹⁴ They may also lose the cardiovascular benefits they have gained, such as improved blood pressure levels, blood glucose control, and lipid profiles. 

The same information has not been established for the oral form, which is newer.

How Much Do These GLP-1 Medications Cost?

According to their websites, the following are the list prices for 30-day supplies of branded Semaglutide in the U.S. as of September 2023:

  • Ozempic: $935.77¹⁵

  • Rybelsus: $935.77¹⁶

  • Wegovy: $1,349.02¹⁷

Exact prices vary depending on insurance coverage, the specific pharmacy, and other factors. A study found that patients pay as much as 68% out-of-pocket for anti-obesity medications.

Notably, it was previously reported that, among Semaglutide clinical study participants, an average of $1,845 was spent per 1% reduction in body weight.¹⁸

Is Oral Semaglutide Safer Than Injectable Semaglutide?

Semaglutide is generally safe when used appropriately. The most common side effects are mild gastrointestinal disturbances. While severe reactions are rare, the following have been reported:

  • Hypoglycemia (below normal blood sugar)

  • Joint and back pain

  • Infection

  • Acute pancreatitis

  • Acute kidney injury

  • Visual impairment in people with diabetes

  • Allergic reactions

  • Acute gallbladder disease

  • Increased heart rate

Both the pill form and injectable may cause these reactions because of their Semaglutide component.¹⁹ That makes them comparable in terms of safety for most people.

However, each intake route has potential side effects that make it risky for people with comorbidities. In the case of oral Semaglutide, it may interact adversely with other oral medications that need to be taken on the same schedule.

For example, patients on thyroxine may experience thyroid hormone elevation from the high rate of absorption in the gut. Those on bone-strengthening bisphosphonates like alendronate are also at risk.

Meanwhile, patients with unique immune sensitivities may develop pain, redness, rashes, and skin lumps from injecting Semaglutide.

Is Oral Semaglutide Easier to Obtain Than Injectable Semaglutide?

While injectables Ozempic and Wegovy are currently on the FDA’s Drug Shortages List, Rybelsus, the oral version of Semaglutide, is not.²⁰ Nevertheless, its high cost makes Rybelsus difficult for many people to access. 

Luckily, many patients are able to get a compounded version of Semaglutide from a state-licensed pharmacist or compounding facility, making access to effective weight loss treatment more convenient and affordable.²¹

Mailed medications being delivered

Compounding entails customizing a prescription medication to an individual patient’s needs. While the law prohibits pharmacies from making generic versions of newly patented medications, compounding them is legal. Compounding pharmacies help address drug shortages by increasing the available supply of certain medications, making them an important part of the U.S. healthcare system.

Ordinarily, the above considerations are the most important when choosing between medications treating the same condition. However, as you can see, oral and injectable Semaglutide have similar benefits and risks. 

A licensed healthcare provider can help you determine which form might be the best option for you based on your individual preferences, other medications you’re taking, and your family medical history.

Are There Other Ways to Administer Semaglutide?

The oral mucosal route has long been explored as an alternative way of administering peptides like GLP-1 RAs.²² The mouth has good circulation because of the many blood vessels supplying it.²³ Medications allowed to sit on the mouth’s surface can reach the bloodstream by overcoming absorption barriers in the mucosal surfaces and blood vessels. Peptides, being big molecules, are usually mixed with permeability enhancers for optimal absorption.

There are two approaches to oral mucosal absorption. One is the buccal approach, or letting the medication stay in contact with the mucosal surface inside the cheek. The other is the sublingual route, or instilling the medicine under the tongue. The sublingual approach is relatively faster because of the thinner mucosal sheet coating the blood vessels in that area. With the right formulation, therapeutic levels of GLP–1 medications can be reached by oral mucosal absorption. 

Presently, there are no commercial buccal or sublingual Semaglutide formulations. 

What Makes the Sublingual Route an Excellent Alternative in Administering Semaglutide?

The sublingual route gets the medication in close contact with the blood vessels. Therefore, the medication’s effects on the body are immediate. Sublingual administration lets you avoid injection reactions and overdosing, thus improving treatment compliance.²⁴ ²⁵

Through the compounding process, a licensed pharmacist’s formulation can help patients avoid many of the potential disadvantages of sublingual administration, like bitterness and slow dissolution. 

To understand the advantages of administering Semaglutide sublingually, let’s compare it to other methods.

Subcutaneous Approach

The subcutaneous route is the most commonly used for Semaglutide. The subcutaneous approach involves needles that, though small, can induce injection reactions. Additionally, the medication’s dose is more difficult to control once injected. 

Pharmacist checking bottle with a clipboard

Oral Ingestion Approach

Second, we have oral ingestion of the medication. As mentioned previously, medication ingested orally is subject to the gut’s digestive enzymes and liver metabolism, which reduces the amount of medication that reaches the target tissues. 

Sublingual administration lets you avoid these limitations. Additionally, individuals who have difficulty swallowing pills with or without water will find the sublingual route convenient. 

Intranasal Approach

GLP-1 RAs may also be taken intranasally, allowing people to avoid the limitations of the subcutaneous and oral methods. However, the nasal mucosa is more prone to irritation than the oral mucosa, making the sublingual route preferable for GLP-1 peptide administration.

For both injectable and oral forms of Compounded Semaglutide, strict adherence and commitment are critical to the treatment’s success. 

How Can Henry Meds Help You Reach Your Health Goals?

If you're struggling to find or afford Semaglutide, Henry Meds can help. Our Compounded Semaglutide treatment programs provide an effective, more affordable alternative to expensive brand-name medications. 

Our platform connects patients with healthcare providers and compounding pharmacies so more people can access the weight management treatment they need.

We try to keep things simple.  With affordable prices and a convenient new patient intake process, new patients can get started in just a few steps.

  • Fill out our online medical intake form

  • Schedule your virtual consultation 

  • Attend a telehealth appointment with your healthcare provider

That’s it.  Any medication prescribed by your provider will be shipped straight to your door.

Choosing Between Semaglutide Pills and Injectables — The First Big Step in Your Weight Loss Journey

Oral vs injectable Semaglutide are comparable in terms of effectiveness and safety. But everyone’s unique, and what’s best for you might not be best for the next person. Before taking any prescription medication, it’s important to always consult with a licensed healthcare professional to weigh the potential risks and benefits.

On the Henry Meds platform, you and your provider will carefully consider all relevant health and personal factors thoroughly. Working with a licensed healthcare professional to develop an individualized treatment program can increase your chances of long-term success.

At Henry Meds, we don’t think people should have to spend their life savings to access the life-changing treatments they need. 

Get started on your weight loss journey today!

To help you trust the information we provide, every article written by Henry Meds relies on peer-reviewed studies and medically-reviewed facts. We ensure that data, ideas, and figures cited are reliable, current, and accurate. Our team of medical reviewers aims to help you cut through the noise with clear and authoritative primary and secondary sources.

Nothing in this article is intended to be prescriptive or medical advice. Talk to your doctor before starting a new diet and exercise plan. The information presented is about our medically supervised weight management programs and is not an advertisement for a specific drug.

Sources

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  6. Singh, G., et al. Wegovy (semaglutide): a new weight loss drug for chronic weight management. Journal of Investigative Medicine. 70(1), 5-13. (2021, October 27).

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