A Research Study Comparing RYBELSUS® to Other Blood Sugar Lowering Tablets in People Living in America With Type 2 Diabetes (REALYSE) (REALYSE)

August 6, 2026 updated by: Novo Nordisk A/S

REALYSE - Comparative Effectiveness of Once-daily Oral Semaglutide Versus Any Other Oral Glucose-lowering Medication in a Real-world Adult Population With Type 2 Diabetes on Metformin Monotherapy in US Based Health Care Systems - a Pragmatic Randomized Trial

This study is comparing the medicine RYBELSUS® to other medicines in people with type 2 diabetes who need extra treatment. All medicines used in this study are tablets which lower blood sugar in people with type 2 diabetes. The purpose of the study is to see how well RYBELSUS® is at lowering blood sugar compared to other tablets when used in addition to metformin. Participants doctor will give participants either RYBELSUS® or any other blood sugar lowering tablets - which treatment participants get is decided by chance. The doctor treating participants diabetes will give participants a prescription for the medicine and tell how to take it. The study will last for about 1 year. Participants will have 2 planned visits with their doctor which are part of the usual routine diabetes management: the first visit is when participants are included in the study, the second visit is a 1-year follow-up visit. In addition, the study personnel will contact participants up to 3 times during this period and to follow-up on information from participant doctors visits. Participant will be asked to respond 3 times to 4 questionnaires via their personal smartphone or tablet or paper if participant do not have access to one during the study. All clinic visits are part of the usual routine diabetes management and are covered by participants health insurance plan. The study team will collect information from these visits recorded in the medical chart. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1018

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Alhambra, California, United States, 91801
        • Stewart Medical Group
      • Costa Mesa, California, United States, 92627
        • FDRC
      • La Jolla, California, United States, 92037
        • Scripps Whittier Diabetes Inst
      • Riverside, California, United States, 92506
        • Raincross Medical Group
    • Florida
      • Miami, Florida, United States, 33175
        • Reyes Clinical Research, Inc
    • Georgia
      • Marietta, Georgia, United States, 30067
        • Urban Family Practice Assoc
      • Marietta, Georgia, United States, 30060
        • DC Research Works
    • Illinois
      • Gillespie, Illinois, United States, 62033
        • Macoupin Research Group
      • Peoria, Illinois, United States, 61603
        • UnityPoint Health-Diabetes Care Center
      • Skokie, Illinois, United States, 60077
        • Endeavor Health
    • North Carolina
      • Burlington, North Carolina, United States, 27215
        • Kernodle Clin Dpt-Pvt Diagnost
      • Charlotte, North Carolina, United States, 28277
        • OnSite Clinical Solutions, LLC_Charlotte
      • Garner, North Carolina, United States, 27529
        • WakeMed Garner Hlthplx
      • Gastonia, North Carolina, United States, 28054
        • Clinical Research of Gastonia
    • North Dakota
      • Fargo, North Dakota, United States, 58104
        • Valley Weight Loss Clinic
    • Ohio
      • Canton, Ohio, United States, 44718
        • Diab & Endo Assoc of Stark Co
      • Columbus, Ohio, United States, 43213
        • Central Ohio Clinical Research LLC
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19114
        • Tristar Clin Investigations, PC
      • Philadelphia, Pennsylvania, United States, 19107-6810
        • Jefferson Endocrinology Assocs
      • Pittsburgh, Pennsylvania, United States, 15236
        • Preferred Primary Care Physicians_Pittsburgh
    • South Carolina
      • Anderson, South Carolina, United States, 29621
        • AnMed Health IMA
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor Scott & White Res Inst
      • New Braunfels, Texas, United States, 78130
        • Hill Country Medical Associates
      • San Antonio, Texas, United States, 78258
        • DCT-Stone Oak
    • Utah
      • St. George, Utah, United States, 84790
        • Chrysalis Clinical Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key inclusion criteria

  • Treatment with metformin as monotherapy prior to eligibility assessment that has failed to result in adequate glycemic control at the discretion of the investigator or treatment provider. However, prior short-term treatment with an oral glucose lowering agent or insulin for up to 14 consecutive days in addition to metformin is allowed if discontinued prior to screening.
  • Current member of a health plan which includes pharmacy benefits.
  • HbA1c greater than or equal to 7% within last 90 days prior to the day of screening or to be taken before randomization.
  • Further intensification with an additional glucose-lowering oral agent including oral semaglutide is indicated according to approved prescribing information to achieve glycemic target at the discretion of the treatment provider.

Key exclusion criteria:

  • Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using contraception.
  • Any disorder which in the investigator's or treatment provider's opinion might jeopardize patient's safety.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: oral semaglutide
All participants are given tablets used in addition to metformin.
Drug: semaglutide
Oral administration The doctor will give a prescription for the medicine and tell how to take it.
Active Comparator: other oral glucose lowering medication
All participants are given tablets used in addition to metformin.
Drug: oral glucose-lowering medications (commercially available)
Oral administration The doctor will give a prescription for the medicine and tell how to take it.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in Glycated Haemoglobin (HbA1c)
Time Frame: Week 0, year 1
Change in HbA1c in percentage from week 0 to year 1 is presented
Week 0, year 1

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Participants Achieving HbA1c Less Than (<) 7.0 Percentage (%) (Yes /No)
Time Frame: At year 1
Participants achieving HbA1c < 7.0% (Yes /No) at year 1 is presented. 'Yes' defines participants who achieved HbA1c < 7.0% and 'No' defines participants who did not achieve HbA1c < 7.0 %.
At year 1
Participants Achieving HbA1c Less Than or Equal to (≤) 6.5% (Yes/No)
Time Frame: At year 1
Participants achieving HbA1c ≤ 6.5% (Yes/No) at year 1 is presented. 'Yes' defines participants who achieved HbA1c ≤ 6.5% and 'No' defines participants who did not achieve HbA1c ≤ 6.5%.
At year 1
Participants Achieving HbA1c <7.0% or at Least 1.0%-Point Reduction in HbA1c (Yes/No)
Time Frame: From Week 0 to year 1
Participants achieving HbA1c < 7.0% or at least 1.0%-point reduction in HbA1c (Yes/No) from week 0 to year 1 is presented. 'Yes' defines participants who achieved HbA1c < 7.0% or reduction of at least 1.0%-point in HbA1c and 'No' defines participants who did not achieve HbA1c < 7.0% or reduction of at least 1.0%-point in HbA1c.
From Week 0 to year 1
Participants Achieving Greater Than or Equal to (≥) 5% Reduction in Body Weight (Yes/No)
Time Frame: From week 0 to year 1
Participants achieving ≥ 5% reduction in body weight (Yes/No) from week 0 to year 1 is presented. 'Yes' defines participants who achieved ≥ 5% reduction in body weight and 'No' defines participants who did not achieve ≥ 5% reduction in body weight.
From week 0 to year 1
Participant Achieving Individualized HbA1c Target Per Healthcare Effectiveness Data and Information Set (HEDIS) Criteria (Yes/No)
Time Frame: At year 1
Participants achieving individualized HbA1c target per HEDIS criteria (< 8.0% if age ≥ 65 years or with defined comorbidities or otherwise < 7.0%) (Yes/No) at year 1 is presented. 'Yes' defines participants who achieved individualized HbA1c target per HEDIS criteria and 'No' defines participants who did not achieve individualized HbA1c target per HEDIS criteria.
At year 1
Participant Achieving HbA1c ≤ Treatment Provider Defined Individualized Target (Yes/No)
Time Frame: At year 1
Participant achieving HbA1c ≤ treatment provider defined individualized target (Yes/No) at year 1 is presented. 'Yes' defines participant who achieved HbA1c ≤ treatment provider defined individualized target and 'No' defines participant who did not achieve HbA1c ≤ treatment provider defined individualized target.
At year 1
Relative Change in Body Weight (%)
Time Frame: Week 0, year 1
Relative change in body weight from week 0 to year 1 is presented.
Week 0, year 1
Change in Body Weight (Lbs)
Time Frame: Week 0, year 1
Change in body weight in pounds (lbs) from week 0 to year 1 is presented.
Week 0, year 1
Time to Treatment Intensification (add-on) or Change (Switch) in Terms of Events
Time Frame: From week 0 to year 1
Time to treatment intensification (add-on) or change (switch) in terms of events from week 0 to year 1 is presented.
From week 0 to year 1
Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc), Relative Treatment Satisfaction Total Score
Time Frame: At year 1
DTSQc relative treatment satisfaction total score measured at year 1 is presented. DTSQc are used to evaluate patient satisfaction with treatment. The measure consists of 8 items, 6 of which assess treatment satisfaction. Scores from the 6 treatment satisfaction items are summed to a total treatment satisfaction score, which ranges from -18 (much less satisfied) to +18 (much more satisfied).
At year 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Novo Nordisk A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Clinical Transparency (dept. 1452), Novo Nordisk A/S

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 18, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 18, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 30, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 30, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 5, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 10, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 6, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NN9924-4558
  • U1111-1253-2577 (Other Identifier: World Health Organization (WHO))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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