FDA approves Novo Nordisk's oral semaglutide for cardiovascular (CV) risk reduction in adults with type 2 diabetes who are at high risk, including those who have not had a prior CV event

USA - English

• USA - English

• Rybelsus^® (semaglutide) tablets 7 mg or 14 mg, the only FDA-approved oral GLP-1 medicine available, now indicated to reduce the risk of major adverse cardiovascular events (MACE) such as CV death, heart attack, or stroke in adults with type 2 diabetes who are at high risk for these events¹
• In the SOUL trial, oral semaglutide 14 mg reduced the risk of MACE by 14% compared to placebo, in addition to standard therapies
• Milestone underscores the robust data supporting oral semaglutide and demonstrates Novo Nordisk's cardiometabolic leadership and commitment to people living with chronic disease

PLAINSBORO, N.J. and BAGSVÆRD, Denmark, Oct. 17, 2025 /PRNewswire/ -- Novo Nordisk announced today that the US Food and Drug Administration (FDA) has approved Rybelsus^®, the only oral GLP-1 medication available, for reducing the risk of major adverse cardiovascular events (MACE) such as cardiovascular (CV) death, heart attack, or stroke in adults with type 2 diabetes who are at high risk for these events, whether they've had a prior CV event or not (primary and secondary prevention). Results of the SOUL trial reinforce the clinical profile of the semaglutide molecule, which has been studied across a variety of therapeutic areas.²    

"Even in the absence of a previous heart attack or stroke, adults with type 2 diabetes face an increased risk of cardiovascular events, underscoring the need for therapies that go beyond managing blood sugar," said John B. Buse, MD, PhD, Distinguished Professor of Medicine, Director of the UNC Diabetes Care Center, and Steering Committee Co-Chair of the SOUL trial. "Having an oral GLP-1 therapy to help improve glycemic control was an innovation in and of itself. This new indication, based on the SOUL data, marks even further advancement and showcases the versatility of semaglutide while expanding options for millions of people."

This new indication makes Rybelsus^® the only oral GLP-1 medicine approved to reduce the risk of MACE in adults with type 2 diabetes who are at high risk for these events. It serves for both primary prevention (reducing the risk of major adverse cardiovascular events by preventing or managing risk factors in adults who are at high risk for these events) and secondary prevention (reducing the risk of another event in people who have had a serious CV event). 

The primary objective of the phase 3b SOUL trial was to evaluate the effects of oral semaglutide 14 mg, in addition to standard of care, on reducing the risk of MACE in adults with type 2 diabetes at high risk for major cardiovascular events. The primary endpoint of the study was the time to first occurrence of MACE (a 3-point composite of CV death, non-fatal myocardial infarction, or nonfatal stroke). MACE events occurred in 579/4825 participants (12.0%) of the semaglutide group and 668/4825 participants (13.8%) of the placebo group (HR 0.86; 95% CI, 0.77-0.96; p=0.006).² Oral semaglutide 14 mg demonstrated a statistically significant 14% relative reduction in risk of MACE at 4 years (2% absolute risk reduction at 3 years) compared with placebo.² These results add to the extensive body of randomized clinical trial and real-world evidence supporting semaglutide.

"As the only FDA-approved GLP-1 therapy in a pill, now recognized for its proven cardiovascular benefits, a new benchmark has been set for future oral innovations," said Dave Moore, Executive Vice President, US Operations of Novo Nordisk Inc. "The semaglutide molecule has consistently demonstrated robust outcomes across multiple, large-scale trials, further reinforcing the already established cardiovascular profile it delivers for patients."

The overall safety profile of oral semaglutide 14 mg in SOUL was consistent with that seen in previous trials, with safety data collection focused on serious adverse events, those of special interest, and those leading to discontinuation.² The most common serious adverse events (SAEs) in the oral semaglutide 14 mg and placebo groups were cardiac disorders (17.8% and 19.8%, respectively) and infections/infestations (15.0% and 16.5%, respectively). SAEs were less common with oral semaglutide 14 mg (47.9%) than with placebo (50.3%), although there was a higher incidence of gastrointestinal disorders with oral semaglutide 14 mg (5.0% versus 4.4%). Adverse events that led to permanent discontinuation of oral semaglutide or placebo occurred in 749 participants (15.5%) in the oral semaglutide group and in 559 participants (11.6%) in the placebo group. Such events were mainly gastrointestinal disorders as well as infections or infestations.²

The FDA initially approved Rybelsus^® in 2019 as the first and only GLP-1 medicine in pill form, along with diet and exercise, to improve glycemic control for adults with type 2 diabetes.¹

Separately, Novo Nordisk has also submitted a supplemental application in the US for a once-daily oral formulation of semaglutide under the trade name Wegovy^® for the treatment of obesity. A decision is expected later this year.

Only Novo Nordisk manufactures FDA-approved semaglutide medicines. Novo Nordisk is continuing to take multiple proactive measures to prevent both unlawful compounded and counterfeit versions of semaglutide. Novo Nordisk believes it is vitally important to make patients aware of the potential dangers of these unsafe and unapproved knockoff alternatives and informed of how to access authentic, FDA-approved Novo Nordisk semaglutide medicines. More information can be found on semaglutide.com.

About SOUL 
SOUL was a multicenter, international, randomized, double-blind, parallel-group, placebo-controlled, phase 3b cardiovascular outcomes trial, with 9,650 participants enrolled. It was conducted to assess the effect of oral semaglutide versus placebo, when added to standard of care, on cardiovascular outcomes in people with type 2 diabetes who are at high risk of MACE (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). The SOUL trial was initiated in 2019 with a mean follow up of 4 years. The primary outcome was time-to-first occurrence of major adverse cardiovascular events (MACE; a composite endpoint consisting of cardiovascular death, heart attack, and stroke).² Oral semaglutide 14 mg demonstrated a statistically significant 14% relative reduction in risk of MACE at 4 years (2% absolute risk reduction at 3 years) compared with placebo.²  

About Rybelsus^® 
Rybelsus^® (oral semaglutide) is a GLP-1 receptor agonist indicated for the treatment of adults with type 2 diabetes mellitus to improve glycemic control as an adjunct to diet and exercise.^3,4 Rybelsus^® is administered once daily and is currently available for use in two therapeutic dosages: 7 mg and 14 mg.^5,6 Rybelsus^® is currently commercially marketed in 45 countries. 2.4 million people have been prescribed Rybelsus^® worldwide.⁷

What is RYBELSUS^®?
 RYBELSUS^® (semaglutide) tablets 7 mg or 14 mg is a prescription medicine used:

• along with diet and exercise to improve blood sugar (glucose) in adults with type 2 diabetes
• to reduce the risk of major cardiovascular events such as heart attack, stroke, or death in adults with type 2 diabetes mellitus who are at high risk for these events

It is not known if RYBELSUS^® is safe and effective for use in children

Important Safety Information
What is the most important information I should know about RYBELSUS^®?
RYBELSUS^® may cause serious side effects, including:

• Possible thyroid tumors, including cancer. Tell your healthcare provider if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. In studies with rodents, RYBELSUS^® and medicines that work like RYBELSUS^® caused thyroid tumors, including thyroid cancer. It is not known if RYBELSUS^® will cause thyroid tumors or a type of thyroid cancer called medullary thyroid carcinoma (MTC) in people

Do not use RYBELSUS^® if:

• you or any of your family have ever had MTC, or if you have an endocrine system condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• you have had a serious allergic reaction to semaglutide or any of the ingredients in RYBELSUS^®. See symptoms of serious allergic reaction in  What are the possible side effects of RYBELSUS^®?"

Before using RYBELSUS^®, tell your healthcare provider if you have any other medical conditions, including if you:

• have or have had problems with your pancreas or kidneys
• have a history of vision problems related to your diabetes
• are scheduled to have surgery or other procedures that use anesthesia or deep sleepiness (deep sedation)
• are pregnant or plan to become pregnant. It is not known if RYBELSUS^® will harm your unborn baby. You should stop using RYBELSUS^® 2 months before you plan to become pregnant
• are breastfeeding or plan to breastfeed. Breastfeeding is not recommended during treatment with RYBELSUS^®

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. RYBELSUS^® may affect the way some medicines work and some medicines may affect the way RYBELSUS^® works.

How should I take RYBELSUS^®?

• Take RYBELSUS^® exactly as your healthcare provider tells you to
• Do not take more than 1 tablet each day
• Take RYBELSUS^® by mouth on an empty stomach in the morning with a sip of plain water (no more than 4 ounces). Do not take RYBELSUS^® with any other liquids besides water
• Do not split, crush, or chew. Swallow RYBELSUS^® whole
• After 30 minutes, you can eat, drink, or take other oral medicines
• If you miss a dose of RYBELSUS^®, skip the missed dose and go back to your regular schedule

What are the possible side effects of RYBELSUS^®?
RYBELSUS^® may cause serious side effects, including:

• inflammation of your pancreas (pancreatitis). Stop using RYBELSUS^® and call your healthcare provider right away if you have severe pain in your stomach area (abdomen) that will not go away, with or without nausea or vomiting. You may feel the pain from your abdomen to your back
• changes in vision. Tell your healthcare provider if you have changes in vision during treatment with RYBELSUS^®
• low blood sugar (hypoglycemia). Your risk for getting low blood sugar may be higher if you use RYBELSUS^® with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. Signs and symptoms of low blood sugar may include: dizziness or lightheadedness, blurred vision, anxiety, irritability or mood changes, sweating, slurred speech, hunger, confusion or drowsiness, shakiness, weakness, headache, fast heartbeat, and feeling jittery
• dehydration leading to kidney problems. Diarrhea, nausea, and vomiting may cause a loss of fluids (dehydration), which may cause kidney problems. It is important for you to drink fluids to help reduce your chance of dehydration. Tell your healthcare provider right away if you have nausea, vomiting or diarrhea that does not go away
• severe stomach problems. Stomach problems, sometimes severe, have been reported in people who use RYBELSUS^®. Tell your healthcare provider if you have stomach problems that are severe or will not go away
• serious allergic reactions. Stop using RYBELSUS^® and get medical help right away, if you have any symptoms of a serious allergic reaction, including swelling of your face, lips, tongue, or throat; problems breathing or swallowing; severe rash or itching; fainting or feeling dizzy; or very rapid heartbeat
• gallbladder problems. Gallbladder problems have happened in some people who take RYBELSUS^®. Tell your healthcare provider right away if you get symptoms of gallbladder problems, which may include: pain in your upper stomach (abdomen), yellowing of skin or eyes (jaundice), fever, and clay-colored stools
• food or liquid getting into the lungs during surgery or other procedures that use anesthesia or deep sleepiness (deep sedation). RYBELSUS^® may increase the chance of food getting into your lungs during surgery or other procedures. Tell all your healthcare providers that you are taking RYBELSUS^® before you are scheduled to have surgery or other procedures

The most common side effects of RYBELSUS ^® may include nausea, stomach (abdominal) pain, diarrhea, decreased appetite, vomiting, and constipation. Nausea, vomiting, and diarrhea are most common when you first start RYBELSUS^®.

Please click here for Prescribing Information and Medication Guide for RYBELSUS®. Please click here for Prescribing Information for Wegovy® including Medication Guide.

About Novo Nordisk
Novo Nordisk is a leading global healthcare company that's been making innovative medicines to help people with diabetes lead longer, healthier lives for more than 100 years. This heritage has given us experience and capabilities that also enable us to drive change to help people defeat other serious chronic diseases such as obesity, rare blood, and endocrine disorders. We remain steadfast in our conviction that the formula for lasting success is to stay focused, think long-term, and do business in a financially, socially, and environmentally responsible way. With a US presence spanning 40 years, Novo Nordisk US is headquartered in New Jersey and employs over 10,000 people throughout the country across 12 manufacturing, R&D and corporate locations in eight states plus Washington DC. For more information, visit  novonordisk-us.com , Facebook , Instagram , and X .

References

1. Rybelsus^® (oral semaglutide) [package insert]. Plainsboro, NJ: Novo Nordisk Inc.
2. McGuire DK, Marx N, Mulvagh SL, et al. Oral semaglutide and cardiovascular outcomes in high-risk type 2 diabetes.N Engl J Med. 2025;392(20):2001-2012.
3. Rybelsus^® (oral semaglutide): US Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213051s023lbl.pdf. Last accessed: October 2025.
4. Rybelsus^® (oral semaglutide): Summary of Product Characteristics. Available at: Rybelsus | European Medicines Agency (EMA). Last accessed: September 2025.
5. Rosenstock J, Allison D, Birkenfeld AL, et al. Effect of additional oral semaglutide vs sitagliptin on glycated haemoglobin in adults with type 2 diabetes uncontrolled with metformin alone or with sulfonylurea: the PIONEER 3 randomized clinical trial. JAMA. 2019;321(15):1466-1480.
6. Rodbard HW, Rosenstock J, Canani LH, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: the PIONEER 2 trial. Diabetes Care. 2019;42(12):2272-2281.
7. Novo Nordisk Data on File. IQVIA Jun'25 Patients R3M Vol. data. 2025.

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