How Does Rybelsus Control Type 2 Diabetes?

Medically Reviewed by Laurel Riemann, PharmD on May 15, 2024
9 min read

The approval of medicines called “glucagon-like peptide (GLP-1) agonists” has led to major changes in how type 2 diabetes is managed. These medicines work in a different way than other medicines used to treat type 2 diabetes. The active ingredient in Rybelsus is semaglutide, which is also found in other products like Ozempic and Wegovy.

People who have type 2 diabetes have an increased amount of sugar in their blood, also called glucose. Increased sugar in your body happens because your body’s insulin doesn’t work as well as it should. Insulin is made by your pancreas and lowers your blood sugar. GLP-1 agonists, like Rybelsus, mimic the body’s own GLP-1 hormone by binding to and activating the GLP-1 receptor.

Previous GLP-1 agonists were only available by injection. Rybelsus (reb-EL-sus) was approved in 2017 as the first and only medication in its class taken by mouth to treat type 2 diabetes. 

Below you’ll find common questions and answers about Rybelsus, and whether it’s right for you. 

Rybelsus lowers your blood sugar in three ways: 

  • It stimulates your pancreas to make insulin after you eat.
  • It prevents your liver from releasing stored sugar.
  • It slows the movement of food through your body.

Take Rybelsus by mouth on an empty stomach, with no more than 4 ounces of plain water. It is important that you take Rybelsus when you first wake up, at least 30 minutes before your first food, drink (outside of plain water), or other medicines you take by mouth. Waiting less than 30 minutes or taking Rybelsus with food, drink (other than plain water), or other medicines you take by mouth can lower how much Rybelsus gets absorbed by your body and can cause Rybelsus not to work as well. Swallow the tablet whole. Do not split, crush, or chew the tablet.

Rybelsus is taken once daily. It comes as a 3-milligram, 7-milligram, and 14-milligram tablet. The 3-milligram once-daily dose helps your body get used to taking the medicine, but it is not likely to lower your blood sugar. Rybelsus 3 milligrams will usually be prescribed to you for 30 days to get your treatment started. Rybelsus 7 milligrams will be usually prescribed to you after Rybelsus 3 mg to lower your blood sugar. Your health care provider may increase your dose to 14 milligrams after you have been on 7 milligrams for at least 30 days, depending on your blood sugar levels and hemoglobin A1c (HbA1c), which is a blood test that measures your blood sugar levels over the past 2 to 3 months. Having a lower HbA1c may lower your risk of having problems from your diabetes. Your health care provider may monitor your HbA1c and can help you set HbA1c goals.  

Clinical studies were done to see if Rybelsus was safe and effective for people with type 2 diabetes. Studies looked at the effect of Rybelsus on blood sugar over time by checking HbA1c. Weight loss was also measured. People could take Rybelsus alone or along with other medicines for type 2 diabetes. Rybelsus was compared with a placebo containing no medicine and against other medicines for type 2 diabetes medicines. The studies included people who were White Americans, African Americans, or Asian Americans, including those who identified as Hispanic or Latino. People in these studies were between 55 and 70 years old, with an average HbA1c between 7% and 10.5%, and an average body weight between 189 and 211 pounds.  

Overall, people taking Rybelsus alone or with other medicines for type 2 diabetes had a lower HbA1c and lost more weight compared with people taking a placebo. Rybelsus was effective regardless of age, gender, race, weight, diabetes duration, or kidney function. Your results may differ from what was seen in clinical studies.

Rybelsus as the only medicine for type 2 diabetes

Rybelsus was compared to placebo among people whose blood sugar was not controlled with diet and exercise. As compared to placebo, more improvement in HbA1c and weight from the beginning of the study to week 26 was seen with Rybelsus. 

 

Rybelsus 7 milligrams

Rybelsus 14 milligrams

Placebo

Average change in HbA1c

-1.2%

-1.4%

-0.3%

Average change in weight

-5.1 pounds

-8.1 pounds

-3.1 pounds

Rybelsus in people with lowered kidney function 

Rybelsus 14 milligrams was compared to placebo in people who were taking a stable dose of other medicines for diabetes including metformin and/or sulfonylurea, or basal insulin with or without metformin in people who had lowered kidney function. As compared to placebo, a greater improvement in HbA1c and body weight from the beginning of the study to week 26 was seen with Rybelsus.

 

Rybelsus 14 milligrams

Placebo

Average change in HbA1c

-1.0%

-0.2%

Average change in weight

-7.5 pounds

-2.0 pounds

 

Rybelsus was compared to placebo among people whose blood sugar was not controlled on insulin with or without another medicine for diabetes called metformin. As compared to placebo, more improvement in HbA1c and body weight from the beginning of the study to week 26 was seen with Rybelsus. 

 

Rybelsus 7 milligrams

Rybelsus 14 milligrams

Placebo

Average change in HbA1c

-0.9%

-1.3%

-0.1%

Average change in weight

-5.3 pounds

-8.1 pounds

-0.9 pounds

 

Rybelsus was also compared with other medicines for type 2 diabetes. In these studies, people were taking other medicines for type 2 diabetes, such as metformin. Below is a summary of how Rybelsus compares to the other medicines it was studied against.

  • Compared to Jardiance (empagliflozin) 25 milligrams once daily, people taking Rybelsus 14 milligrams once daily saw more lowering of HbA1c. People taking either Rybelsus or Jardiance lost a similar amount of weight.  
  • Compared to Januvia (sitagliptin) 100 milligrams once daily, people taking Rybelsus 7 milligrams or 14 milligrams once daily saw more lowering of HbA1c and lost more weight.
  • Compared to Victoza (liraglutide) 1.8 milligrams injected once daily, people taking Rybelsus 14 milligrams once daily saw a similar HbA1c lowering but lost more weight.

Rybelsus plus other medicines for type 2 diabetes 

Rybelsus 14 milligrams was compared to empagliflozin (at a dose of 25 milligrams) among people who were uncontrolled on another medicine used for type 2 diabetes called metformin. As compared to empagliflozin, more improvement in HbA1c from the beginning of the study to week 26 was seen with Rybelsus. People who got either Rybelsus or empagliflozin lost a similar amount of weight.

 

Rybelsus 14 milligrams

Empagliflozin 25 milligrams

Average change in HbA1c

-1.3%

-0.9%

Average change in weight

-8.4 pounds

-8.1 pounds

 

Rybelsus was compared to sitagliptin (at a dose of 100 milligrams). People were uncontrolled on other medicines for diabetes (metformin with or without a medicine called a sulfonylurea such as glimepiride or glipizide). As compared to sitagliptin, more improvement in HbA1c and body weight from the beginning of the study to week 26 was seen with Rybelsus.

 

Rybelsus 7 milligrams

Rybelsus 14 milligrams

Sitagliptin 100 milligrams

Average change in HbA1c

-1.0%

-1.3%

-0.8%

Average change in weight

-4.8 pounds

-6.8 pounds

-1.3 pounds

 

Rybelsus 14 milligrams was compared to a medicine for type 2 diabetes called liraglutide (at a dose of 1.8 milligrams) and was also compared to placebo. People were uncontrolled on other medicines for diabetes called metformin with or without a medicine called an SGLT-2 inhibitor (bexagliflozin, canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin). As compared to placebo, more improvement in HbA1c and body weight from the beginning of the study to week 26 was seen with Rybelsus. The effect of Rybelsus and liraglutide on HbA1c was similar, but people lost more weight with Rybelsus.

 

Rybelsus 14 milligrams

Liraglutide 1.8 milligrams

Placebo

Average change in HbA1c

-1.2%

-1.1%

-0.2%

Average change in weight

-9.7 pounds

-6.8 pounds

-1.1 pounds

You can tell if Rybelsus is working when you start to see your blood sugar levels and your HbA1c fall. Based on the clinical studies, Rybelsus may show its full HbA1c-lowering effects after a few months. Talk to your health care provider about monitoring your blood sugar levels at home. Consider making a blood sugar log/diary that you can record your blood sugar readings in to bring to your visits with your health care provider. Your health care provider will likely monitor your HbA1c while you are on Rybelsus and may increase your Rybelsus dose, add another medicine for type 2 diabetes, or change you to another medicine for type 2 diabetes.

The most common side effects with Rybelus are nausea, stomach pain, diarrhea, decreased appetite, vomiting, and constipation. Nausea, vomiting, and diarrhea are the most common when you first start Rybelsus. If you are having these side effects, make sure to drink plenty of water to avoid becoming dehydrated. Call your health care provider if you are having vomiting or diarrhea that is not getting better.

You should take the lowest dose of Rybelsus that works to control your blood sugar to avoid side effects. Here are more ways to manage side effects from Rybelsus.

  • Avoid greasy, sweet, and spicy foods. 
  • Eat smaller and more frequent meals. 
  • Eat slowly. 
  • Do not lie down after eating. 
  • Maintain a low-fat diet, which includes eating soup and yogurt. 
  • Eat bland foods such as crackers and rice. 
  • Stay hydrated.
  • Avoid strong smells such as from cooking, perfume, or smoke. 

These are not all of the side effects of Rybelsus. Talk with your health care provider if you are having symptoms that bother you. You can also report side effects to the FDA at 800-FDA-1088.

Stop Rybelsus and call your health care provider right away if you have severe stomach pain that will not go away. The pain may radiate to your back, and you may have vomiting. These may be signs of inflammation of the pancreas called pancreatitis. Make sure your health care provider knows if you develop pancreatitis. Rybelsus was not studied in people who had pancreatitis, and the medicine should not be continued for people who develop it.

Talk with your health care provider if you want to become pregnant. Rybelsus should be stopped at least 2 months before you become pregnant. After your last dose, Rybelsus takes about 5 weeks to leave the body. 

Rybelsus works by slowing down the movement of food through your body. Because of this, it may affect how other medicines that you take by mouth are absorbed. Talk with your health care provider if you feel that other medicines that you take by mouth are not working as well as they used to while taking Rybelsus.

Rybelsus also works by stimulating insulin production after you eat and prevents your liver from releasing stored sugars. Low blood sugar (hypoglycemia) may happen if you take Rybelsus with insulin or some other medicines for diabetes such as a sulfonylurea. Talk to your health care provider about low blood sugar, so you know what number is too low. 

If your blood sugar gets too low, eat some sugar. Sugar sources include glucose tablets, glucose gel, 4 ounces of juice or non-diet soda, or a tablespoon of sugar, honey, or corn syrup. Call your health care provider if you have any of the following symptoms of low blood sugar or if your blood glucose goes too low. 

  • Dizziness
  • Shakiness
  • Sweating
  • Anxiety
  • Crankiness or mood changes
  • Hunger
  • Fast heartbeat
  • Sleepiness
  • Headache
  • Tingling in your cheeks, lips, or tongue

Rybelsus requires a prescription from a health care provider. You can get it at any pharmacy.

There is a Rybelsus Savings Card available from the manufacturer that may allow you to pay as little as $10 for your prescription. Whether you are eligible depends on the type of insurance plan you have and if your insurance covers Rybelsus. You can find out more at www.rybelsus.com/savings-and-support.html, by texting READY to 21848, or by calling 833-275-2233 to ask for assistance with the savings offer. The Rybelsus website also provides you with more information about Rybelsus and ways for you to talk to a diabetes health coach for free.   

For questions about cost, insurance coverage, or any other questions related to Rybelsus, you can also call the manufacturer at 833-GLP-PILL.