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by Kyle Davies on Jul 03, 2025

What Is Rybelsus: A Guide to the Oral GLP-1 Medication

Following the success of Ozempic, the first type 2 diabetes (T2D) medication based on semaglutide, Novo Nordisk expanded its glucagon-like peptide-1 (GLP-1) receptor agonist line with Rybelsus, which marked a major milestone as the first oral treatment using this compound.

Taken as a once-daily tablet, Rybelsus offers convenient and effective blood sugar control, outperforming drugs such as empagliflozin and sitagliptin. In trials, a 14 mg dose of Rybelsus reduced glycosylated hemoglobin (HbA1c) by 1.3–1.4 percentage points (pp) over 26 weeks, compared to 0.8–0.9 pp achieved by these medications. Many patients also experienced weight loss, shedding around 4.5 kg (or 5% of body weight), with higher doses leading to even greater reductions. Data also suggests added cardiovascular benefits, including fewer non-fatal heart attacks and strokes in people with type 2 diabetes (T2D) and heart or kidney disease.

What should you know about a tablet that controls blood sugar, supports weight loss, and possibly protects the heart?

A GLP-1 Tablet at a Glance: What Is Rybelsus and How Does it Work?

Rybelsus is an oral medication for type 2 diabetes that contains semaglutide as its active ingredient. It works as a synthetic GLP-1 receptor agonist, imitating the effects of the body’s natural incretin hormone. Rybelsus helps lower blood sugar without causing hypoglycaemia by increasing insulin release from the pancreas only when blood sugar levels are high.

At the same time, the drug reduces the release of glucagon, a hormone that signals the liver to produce glucose and release it into the bloodstream. This helps to prevent unnecessary rises in blood sugar.

Rybelsus also slows down the rate at which food moves from the stomach to the intestines. This also reduces the rise in blood glucose after meals while maintaining a prolonged feeling of fullness, which stabilises sugar levels in the blood and reduces overall food consumption. As semaglutide also plays a role in appetite regulation, Rybelsus can support weight loss efforts. High doses of Rybelsus (25mg) is in the final stage to be approved for weight loss.

Although semaglutide is structurally similar to natural human GLP-1, sharing 94% of its amino acid sequence, it has been modified to resist rapid breakdown in the body. While natural GLP-1 is active for only a few minutes, semaglutide has a much longer half-life of about seven days. However, because Rybelsus is taken orally, its absorption can vary compared to injectable semaglutide, and daily dosing is required to maintain therapeutic levels in the body.

What Is Rybelsus Used For: Approved Purposes and Patient Population

Although Rybelsus has shown promising cardiovascular benefits, it is officially approved only for managing blood sugar levels in adults with type 2 diabetes. It works best when combined with a healthy diet and regular exercise and is authorised for monotherapy or in combination with other antidiabetic drugs use in adults with T2D who:

Have not achieved adequate blood sugar control with other medications.
Are intolerant to other non-GLP-1 T2D drugs like metformin or sulfonylureas.
Are newly diagnosed or have never tried any other T2D medication.
Can take oral medication and prefer a tablet over injections.

Rybelsus is not approved for people with:

Type 1 diabetes (T1D), as for its efficiency, it requires insulin production, which is absent in T1D.
Diabetic ketoacidosis (DKA), because Rybelsus does not provide the rapid insulin replacement needed for this serious complication, characterised by severe insulin deficiency and high ketone levels in the blood.
A personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2), conditions linked to a higher risk of thyroid C-cell tumours. This restriction is based on preclinical studies in rodents that showed an increase in these tumours related to the dose and length of treatment..
A history of pancreatitis, as the safety of Rybelsus has not been specifically studied in this group

Is Rybelsus used for weight loss?

Many patients do experience weight loss with Rybelsus, the outcome supported by studies, in which individuals with type 2 diabetes lost over a six-month period:

An average of 2.3 kg on the 7 mg dose.
An average of 3.7 kg on the 14 mg dose.

However, Rybelsus is not officially yet approved by the FDA for weight loss, this is expected end of 2025 or start 2026. For that purpose, more potent semaglutide-based medications, such as Wegovy, are prescribed.

R1 and R2 Rybelsus Tablets and Their Ingredients

Rybelsus comes in two formulations, R1 and R2, both containing semaglutide but with different inactive ingredients that affect the amount of drug absorbed and available to act in the body, known as bioavailability. Thus, R1 and R2 not interchangeable.

Formulation R1 is the original version approved by the U.S. Food and Drug Administration (FDA) in 2019. These tablets are oval-shaped, debossed with “3”, “7”, or “14” on one side and “novo” on the other. They come in strengths of 3 mg, 7 mg, and 14 mg.

Key inactive ingredients in R1 include microcrystalline cellulose, povidone K90, and salcaprozate sodium (SNAC). The latter helps semaglutide absorb in the gut.

To improve the R1’s bioavailability, which ranges from about 0.4% to 1%, Novo Nordisk introduced optimised formulation R2, approved in 2024.

R2 Rybelsus tablets are round, debossed with “1.5”, “4”, or “9” on one side and “novo” on the other. They have a simpler inactive ingredient profile, containing only SNAC and magnesium stearate, and achieve higher bioavailability of approximately 1% to 2%. This allows R2 to deliver similar therapeutic effects at lower doses compared to R1. For instance, 4 mg of R2 can potentially provide an effect similar to 7 mg of R1.

Both formulations are currently available on the market.

Rybelsus Treatment Schedule

Similarly to other semaglutide-based medications, Rybelsus should be introduced to the body gradually to allow for the adjustment to the effects of this medication.

The dosing schedule for this medication depends on whether the R1 or R2 formulation is prescribed. However, regardless of the Rybelsus variation, doses are typically increased at minimum 30-day intervals. The usual regimen looks in the following way:

1. Days 1–30

The goal at this stage is not to lower blood sugar yet, but to help the body tolerate semaglutide.

3 mg once daily for R1.
1.5 mg once daily for R2.

2. Days 31–60

The medical provider may decide to increase the dosage to levels that begin providing therapeutic benefits.

7 mg once daily for R1.
4 mg once daily for R2.

3. Day 61 and beyond

The further approach depends on the patient’s condition.

7 mg of R1 or 4 mg of R2 daily if blood sugar is well controlled.
14 mg of R1 or 9 mg of R2 daily if additional control is needed.

Important instructions

The Rybelsus tablets should be taken once a day, first thing in the morning, on an empty stomach. It is crucial to wait at least 30 minutes before eating, drinking, or taking any other medicines.

The tablet must be swallowed whole, without crushing, chewing or breaking, with a small amount of water, not exceeding 120 mL.

It is important to take only one tablet per day and never increase the dose before completing 30 days on the previous dose.

Rybelsus’ Side Effects

Gastrointestinal issues such as abdominal pain, decreased appetite, vomiting, and constipation affect at least 5% of patients taking Rybelsus. Side effects like diarrhoea and nausea are particularly common, with diarrhoea affecting up to 20% of patients. Some users also report dizziness, headaches, and fatigue.

Serious side effects are uncommon but can still occur. These include:

Inflammation of the pancreas (pancreatitis).
Low blood sugar (hypoglycaemia), especially when Rybelsus is taken with other type 2 diabetes medications.
Kidney problems of varying severity, with increased risk if the patient experiences vomiting and dehydration.
Gallbladder issues such as cholecystitis and gallstones.
Changes in vision.
Serious allergic reactions, including rash, swelling, and difficulty breathing.
A possible increased risk of thyroid C-cell tumours, observed in rodent studies, though the risk in humans is unknown.

Do Rybelsus side effects go away?

Most side effects of Rybelsus are mild and tend to settle within weeks, after the body adapts to the medication. Common side effects such as nausea, vomiting, diarrhoea, abdominal pain, bloating, heartburn, and constipation are usually short-lived and often ease with continued use. But for some patients, the side effects are serious and continue for a longer time.

Rybelsus Success Starts with Consistency

Progress with Rybelsus does not happen overnight and requires taking the medication daily, exactly as prescribed, to maintain consistent levels in your system and support stable blood sugar. However, gastrointestinal side effects, especially early on, can be discouraging.

Fortunately, this discomfort can often be eased with extra care during the treatment.

Incorporating a probiotic specifically formulated for GLP-1 users, opting for a balanced, nourishing, yet gentle diet, staying well hydrated throughout the day, and exercising regularly can make a real difference on the journey to health.

Learn more about Forte80™

This article has been written with information taken from supported scientific research, and its purpose is purely educational. It should not be intended as medical advice or be used in personal diagnoses. Individuals on GLP-1 weight loss drugs should work closely with healthcare providers to develop a comprehensive, holistic health plan. With proper support, including targeted supplementation for digestive health, many more people may be able to benefit from these groundbreaking medications without sacrificing comfort or quality of life.

References:

What Is Rybelsus: A Guide to the Oral GLP-1 Medication

A GLP-1 Tablet at a Glance: What Is Rybelsus and How Does it Work?