Oral GLP-1 medication for type 2 diabetes

If you have type 2 diabetes, your body still makes insulin but either doesn’t produce enough or can’t use it effectively. This is called insulin resistance, which can lead to high blood sugar and cause chronic health problems.

Injectable medications are available to help those with insulin resistance, including a group of drugs called GLP-1 receptor agonists. Recently, the U.S. Food and Drug Administration (FDA) approved an oral GLP-1 formulation called Rybelsus (semaglutide) for the treatment of type 2 diabetes. This is especially helpful for people who don’t want to use an injectable medicine to keep their blood sugar under control. 

Glucagon-like peptide-1 receptor agonists (or GLP-1, for short) work by mimicking a hormone in the body called glucagon-like peptide 1. This hormone stimulates your body to release insulin after eating––a  process crucial to keeping blood glucose levels stable (Novo Nordisk, 2021). 

Oral GLP-1 receptor agonist medications also slow down the speed at which food travels from your stomach to the small intestine. This helps you feel fuller for longer and might lead to weight loss. For this reason, some GLP-1s––like liraglutide and semaglutide––are used to treat obesity by lowering body weight. Others are used to prevent cardiovascular events (like heart disease and high blood pressure) in people with type 2 diabetes.

There are many drugs in the GLP-1 class, however, most are only available as injectable medications. This may make these medications challenging or unappealing to some individuals, as the medications need to be refrigerated and injected subcutaneously (under the skin). 

Recently, the first oral GLP-1 agonist called Rybelsus (semaglutide) was approved by the FDA. Rybelsus helps keep hemoglobin A1C (HbA1c) levels in check, a sign that blood sugar levels are controlled over time. Rybelsus is available with a prescription from a healthcare provider. Since it’s a newer medication for diabetes care, it's only available as a brand name at this time (Novo Nordisk, 2021). 

Oral semaglutide treats elevated blood sugar levels in people with type 2 diabetes mellitus. It may be an effective option when other medications haven’t helped. To get the full benefits, Rybelsus should be taken in tandem with a healthy diet and regular exercise.

Rybelsus and the other GLP-1 agonists can’t be used to treat type 1 diabetes. Because injectable semaglutide carries a risk for pancreatitis (inflammation of the pancreas), Ryblesus hasn’t been studied in people with a history of this condition so we don’t know how it would affect them (Novo Nordisk, 2021).

All medications have a risk of side effects. Because Rybelsus slows down how quickly food leaves the stomach, the most common adverse reactions reported with Rybelsus were gastrointestinal and included (Novo Nordisk, 2021):

• Nausea

• Stomach pain

• Diarrhea

• Decreased appetite

• Vomiting

• Constipation

Other less common but potentially serious side effects include:

• Risk of thyroid tumors

• Pancreatitis

• Complications in people with diabetic eye disease

• Low blood sugar (when used with insulin or other medications that lower blood sugar)

• Kidney disease

• Allergic reactions

Rybelsus comes as oral tablets available in 3 mg, 7 mg, and 14 mg doses. These tablets should be taken whole, not cut, crushed, or chewed.

You’ll typically start on the lowest dose of oral semaglutide. This dose is then usually increased every 30 days until you reach the level that best controls your blood sugar. Be sure to follow the plan recommended by your healthcare provider. 

Take Rybelsus first thing in the morning with no more than 4 ounces of plain water. Wait at least 30 minutes before consuming any food, beverages, or other medicines. This is important because it could change how your body absorbs the drug and alter its effects. Because Rybelsus slows how quickly your stomach empties, it may also affect the absorption of other medications (Novo Nordisk, 2021). 

You should not take Rybelsus if you’ve had an allergic reaction to Rybelsus, Ozempic, or Wegovy (the last two are injectable forms of semaglutide). 

Studies have shown that GLP-1 agonists can cause thyroid tumors in rats. Researchers don’t yet know if humans have the same risk. To be safe, don’t take any GLP-1s if you have a personal or family history of thyroid cancer or a condition called multiple endocrine neoplasia type 2.

Tell your healthcare provider if you have any of the following symptoms, which could indicate a problem with your thyroid (Novo Nordisk, 2021):

• A lump or swelling in your neck

• Hoarseness

• Trouble swallowing

• Shortness of breath

It isn’t common, but Rybelsus can cause complications for people with certain health conditions including (Novo Nordisk, 2021):

• Pancreatitis

• Diabetic retinopathy (damage to the eye from diabetes)

• Hypoglycemia

• Renal (kidney) problems

It’s not recommended to take this medication while you’re pregnant or breastfeeding. Tell your healthcare provider if you are pregnant or are planning to become pregnant so they can recommend other diabetes treatments during this time. Ideally, you should stop taking oral semaglutide at least two months before trying for a baby to ensure the drug has left your system. 

There also have been no clinical trials to see if Rybelsus is safe or effective for people under the age of 18 (Novo Nordisk, 2021).

Oral GLP-1 medications like Rybelsus have similar drug interactions as the injectable versions. 

Rybelsus slows down the rate at which food leaves your stomach. If you take other types of oral medications at the same time, it may change how your body absorbs them. Tell your healthcare provider about any drugs you take including prescription, over-the-counter, vitamins, and herbal supplements (Novo Nordisk, 2021).

Your healthcare provider might instruct you to change the time of day when you take other medications or supplements. They also might monitor your blood levels more closely to make sure each medication is at a therapeutic level.

There is a slightly higher risk of a low blood sugar episode if you combine oral semaglutide with injectable insulin or drugs that trigger insulin secretion (sulfonylureas). If you already take medications to lower blood sugar, your healthcare provider might lower their dosages to reduce the risk of hypoglycemia.

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Current version

March 02, 2022

Written by

Ellyn Vohnoutka, BSN, RN

Fact checked by

Steve Silvestro, MD

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About the medical reviewer

Steve Silvestro, MD, Ro

Dr. Steve Silvestro is a board-certified pediatrician and Associate Director, Clinical Content & Education at Ro.